Antifungal therapy in ICU prophylaxis pre-emptive and targeted

Is it applicablewhen how

Antifungal de-escalation

The case for antifungal stewardship

bull Dr Rafael Zaragoza

Conflicts

bull Pfizer

bull Astellas

bull MSD

bull Gilead

bull Cephalon

SECOND RECOMMENDATION

bull Enjoy City of

Sciences and arts

ndash Opera house

ndash Hemisferic

ndash Sciences museum

ndash Agora

Allaacute vamoshellip

A new schemehellip Invasive Candidiasis in ICU

The case for antifungal stewardship

bull httpwwwdisfrutalogratiscomcochesoporto2jpg

bull Introduction and definition

How to do it

bull Is de-escalation a real practise

bull Is an early broad spectrum

antifungal treatment needed

bull Do we need it Fluconazole

bull Which situations

bull NEVER

bull SOMETIMES

bull ALWAYS

bull When can we step down

ndash If case of proven IC

ndash If IC are not proven

bull Take home messages

Antimicrobial optimization strategies in ICU

GuidelinesProtocols

Restricting the hospital formulary

Scheduled changes in antibiotic

Combining antibiotic therapy

Antibiotic rotation

Area-specific antimicrobial therapy

Antimicrobial de-escalation

Kollef MH Crit Care 20015 189-95

INTRODUCTION Antimicrobial stewardship (AMS) has overwhelmingly focussed on antibiotics

while antifungal agents have been largely neglected despite the few published audits of antifungal drug use demonstrating clear deficiencies in prescibing behavior

Invasive fungal diseases (IFDs) have a lower institutional incidence relative to infections caused by multiresistant bacteria but their health and economic burden are substantial

Pharmacy costs inclusive of antifungal agents are a major determinant of IFD-attributable hospital cost High drug costs and the toxicities of antifungal agents are the principal rationale for AFS while antifungal resistance is an emerging but less prevalent issue

Nonculture-based tests may enhance AFS but refinement of both target populations and clinical pathways incorporating their use is required Performance indicators including structural process and outcome measures are integral for demonstrating the value of AFS programmes

Ananda-Rajah MR Slavin MA Thursky KT

Curr Opin Infect Dis 2012 Feb25(1)107-15

De-escalation of antibiotic therapy Concept

ldquoCould be considered as a strategy to balance the need to provide adequate initial antibiotic treatment of high risk patients with the avoidance of unnecessary antibiotic utilization which promotes resistancerdquo

Inadequate empirical antibitibic therapy and ICU-Bacteremia

6229

0

50

100

I EAT NO I EAT

I nhospital

Mortality

Ibrahim et al Chest 2000 118 146-155

N= 492 Candida spp VRE meticilin resistant S aureus CNS Pseudomonas aeruginosa

IEAT= 299

plt 0001

Inadequate empirical antibitibic therapy and ICU-Bacteremia

30235

0

10

20

30

I EAT NO-I EAT Related

mortality

N= 166 CNS Acinetobacter baumannii Pseudomonas aeruginosa Candida spp

Zaragoza R et al Clin Microbiol Infect 2003 May 9(5)412-418

IEAT= 235

pgt005

APPROACH TO ANTIFUNGAL TREATMENT

Pre-emptive and Empirical Therapy ICCd

iquestPrevious azol`s use +- clinical unstable (MOF severe sepsis) +- suspected or previous infection by C krusei o C glabrata +- multiple colonization by no-C albicans spp +- ICU stay and risk factors (drug-interactions kind of patient pe transplantation peritonitis)

-Fluconazole 400-800 mg IVd If possible switching to oral therapy (400 mgd)

We must considered AF rapid broad spectrum and PKPD

optimized

Yes NO

-Anidulafungin 200 mg24 (d1)+100 mg d -Caspofungin 70 mg24 h (d1) + 50 mg d -Micafungina 150 mg24 hs - Amphotericin B-Lipidic Complex 3-5 mgkgd - Amphotericin B- Lipossomal 3 mgkgd - Voriconazol e iv 6 mgkg12h (d1) + 4 mgkg12h

EVEN POSSIBLE DE-ESCALATION

Zaragoza R Pemaacuten J J Invasive Fungal Infect 2007150-58

Antifungal de-escalation strategy

Initially a broad spectrum antitungal treatment is administrated until the agent of infection was identified

Echinocandins AMPHOTERICINS

Microbiogical data

Patientacutes physician criteria

Maintenance of broad spectrum combination

DT Switching to a narrow spectrum

Guery ICM2008

Candidemia pacientes no-neutropenicos De-escalation IDSA 2008

De-escalation even it`s possible (I-A)

Targeted Treatment of Candidaemia

Echinocandins

Compound SoR QoE Reference Comment

Anidulafungin

200100

A I Reboli NEJM 2007 bull Broad spectrum

bull Resistance rare

bull Fungicidal

bull Local epidemiology

bull C parapsilosis C krusei

bull Safety profile

bull Less drug-drug interactions

than caspofungin

Caspofungin

7050

A I Mora-Duarte NEJM 2002

Pappas CID 2007

bull Largely as above

Micafungin

100

A I Kuse Lancet 2007

Pappas CID 2007

bull Largely as above

bull Consider EMA warning label

Search for

Limits PreviewIndex History Clipboard Details

1 ORIGINAL

ARTICLE found

DE ESCALATION THERAPY AND CANDIDIASIS

0Pb8X13qPubMedpubmedGoSearch4DocSum200

Conflicts

bull Pfizer

bull Astellas

bull MSD

bull Gilead

bull Cephalon

SECOND RECOMMENDATION

bull Enjoy City of

Sciences and arts

ndash Opera house

ndash Hemisferic

ndash Sciences museum

ndash Agora

Allaacute vamoshellip

A new schemehellip Invasive Candidiasis in ICU

The case for antifungal stewardship

bull httpwwwdisfrutalogratiscomcochesoporto2jpg

bull Introduction and definition

How to do it

bull Is de-escalation a real practise

bull Is an early broad spectrum

antifungal treatment needed

bull Do we need it Fluconazole

bull Which situations

bull NEVER

bull SOMETIMES

bull ALWAYS

bull When can we step down

ndash If case of proven IC

ndash If IC are not proven

bull Take home messages

Antimicrobial optimization strategies in ICU

GuidelinesProtocols

Restricting the hospital formulary

Scheduled changes in antibiotic

Combining antibiotic therapy

Antibiotic rotation

Area-specific antimicrobial therapy

Antimicrobial de-escalation

Kollef MH Crit Care 20015 189-95

INTRODUCTION Antimicrobial stewardship (AMS) has overwhelmingly focussed on antibiotics

while antifungal agents have been largely neglected despite the few published audits of antifungal drug use demonstrating clear deficiencies in prescibing behavior

Invasive fungal diseases (IFDs) have a lower institutional incidence relative to infections caused by multiresistant bacteria but their health and economic burden are substantial

Pharmacy costs inclusive of antifungal agents are a major determinant of IFD-attributable hospital cost High drug costs and the toxicities of antifungal agents are the principal rationale for AFS while antifungal resistance is an emerging but less prevalent issue

Nonculture-based tests may enhance AFS but refinement of both target populations and clinical pathways incorporating their use is required Performance indicators including structural process and outcome measures are integral for demonstrating the value of AFS programmes

Ananda-Rajah MR Slavin MA Thursky KT

Curr Opin Infect Dis 2012 Feb25(1)107-15

De-escalation of antibiotic therapy Concept

ldquoCould be considered as a strategy to balance the need to provide adequate initial antibiotic treatment of high risk patients with the avoidance of unnecessary antibiotic utilization which promotes resistancerdquo

Inadequate empirical antibitibic therapy and ICU-Bacteremia

6229

0

50

100

I EAT NO I EAT

I nhospital

Mortality

Ibrahim et al Chest 2000 118 146-155

N= 492 Candida spp VRE meticilin resistant S aureus CNS Pseudomonas aeruginosa

IEAT= 299

plt 0001

Inadequate empirical antibitibic therapy and ICU-Bacteremia

30235

0

10

20

30

I EAT NO-I EAT Related

mortality

N= 166 CNS Acinetobacter baumannii Pseudomonas aeruginosa Candida spp

Zaragoza R et al Clin Microbiol Infect 2003 May 9(5)412-418

IEAT= 235

pgt005

APPROACH TO ANTIFUNGAL TREATMENT

Pre-emptive and Empirical Therapy ICCd

iquestPrevious azol`s use +- clinical unstable (MOF severe sepsis) +- suspected or previous infection by C krusei o C glabrata +- multiple colonization by no-C albicans spp +- ICU stay and risk factors (drug-interactions kind of patient pe transplantation peritonitis)

-Fluconazole 400-800 mg IVd If possible switching to oral therapy (400 mgd)

We must considered AF rapid broad spectrum and PKPD

optimized

Yes NO

-Anidulafungin 200 mg24 (d1)+100 mg d -Caspofungin 70 mg24 h (d1) + 50 mg d -Micafungina 150 mg24 hs - Amphotericin B-Lipidic Complex 3-5 mgkgd - Amphotericin B- Lipossomal 3 mgkgd - Voriconazol e iv 6 mgkg12h (d1) + 4 mgkg12h

EVEN POSSIBLE DE-ESCALATION

Zaragoza R Pemaacuten J J Invasive Fungal Infect 2007150-58

Antifungal de-escalation strategy

Initially a broad spectrum antitungal treatment is administrated until the agent of infection was identified

Echinocandins AMPHOTERICINS

Microbiogical data

Patientacutes physician criteria

Maintenance of broad spectrum combination

DT Switching to a narrow spectrum

Guery ICM2008

Candidemia pacientes no-neutropenicos De-escalation IDSA 2008

De-escalation even it`s possible (I-A)

Targeted Treatment of Candidaemia

Echinocandins

Compound SoR QoE Reference Comment

Anidulafungin

200100

A I Reboli NEJM 2007 bull Broad spectrum

bull Resistance rare

bull Fungicidal

bull Local epidemiology

bull C parapsilosis C krusei

bull Safety profile

bull Less drug-drug interactions

than caspofungin

Caspofungin

7050

A I Mora-Duarte NEJM 2002

Pappas CID 2007

bull Largely as above

Micafungin

100

A I Kuse Lancet 2007

Pappas CID 2007

bull Largely as above

bull Consider EMA warning label

Search for

Limits PreviewIndex History Clipboard Details

1 ORIGINAL

ARTICLE found

DE ESCALATION THERAPY AND CANDIDIASIS

0Pb8X13qPubMedpubmedGoSearch4DocSum200

SECOND RECOMMENDATION

bull Enjoy City of

Sciences and arts

ndash Opera house

ndash Hemisferic

ndash Sciences museum

ndash Agora

Allaacute vamoshellip

A new schemehellip Invasive Candidiasis in ICU

The case for antifungal stewardship

bull httpwwwdisfrutalogratiscomcochesoporto2jpg

bull Introduction and definition

How to do it

bull Is de-escalation a real practise

bull Is an early broad spectrum

antifungal treatment needed

bull Do we need it Fluconazole

bull Which situations

bull NEVER

bull SOMETIMES

bull ALWAYS

bull When can we step down

ndash If case of proven IC

ndash If IC are not proven

bull Take home messages

Antimicrobial optimization strategies in ICU

GuidelinesProtocols

Restricting the hospital formulary

Scheduled changes in antibiotic

Combining antibiotic therapy

Antibiotic rotation

Area-specific antimicrobial therapy

Antimicrobial de-escalation

Kollef MH Crit Care 20015 189-95

INTRODUCTION Antimicrobial stewardship (AMS) has overwhelmingly focussed on antibiotics

while antifungal agents have been largely neglected despite the few published audits of antifungal drug use demonstrating clear deficiencies in prescibing behavior

Invasive fungal diseases (IFDs) have a lower institutional incidence relative to infections caused by multiresistant bacteria but their health and economic burden are substantial

Pharmacy costs inclusive of antifungal agents are a major determinant of IFD-attributable hospital cost High drug costs and the toxicities of antifungal agents are the principal rationale for AFS while antifungal resistance is an emerging but less prevalent issue

Nonculture-based tests may enhance AFS but refinement of both target populations and clinical pathways incorporating their use is required Performance indicators including structural process and outcome measures are integral for demonstrating the value of AFS programmes

Ananda-Rajah MR Slavin MA Thursky KT

Curr Opin Infect Dis 2012 Feb25(1)107-15

De-escalation of antibiotic therapy Concept

ldquoCould be considered as a strategy to balance the need to provide adequate initial antibiotic treatment of high risk patients with the avoidance of unnecessary antibiotic utilization which promotes resistancerdquo

Inadequate empirical antibitibic therapy and ICU-Bacteremia

6229

0

50

100

I EAT NO I EAT

I nhospital

Mortality

Ibrahim et al Chest 2000 118 146-155

N= 492 Candida spp VRE meticilin resistant S aureus CNS Pseudomonas aeruginosa

IEAT= 299

plt 0001

Inadequate empirical antibitibic therapy and ICU-Bacteremia

30235

0

10

20

30

I EAT NO-I EAT Related

mortality

N= 166 CNS Acinetobacter baumannii Pseudomonas aeruginosa Candida spp

Zaragoza R et al Clin Microbiol Infect 2003 May 9(5)412-418

IEAT= 235

pgt005

APPROACH TO ANTIFUNGAL TREATMENT

Pre-emptive and Empirical Therapy ICCd

iquestPrevious azol`s use +- clinical unstable (MOF severe sepsis) +- suspected or previous infection by C krusei o C glabrata +- multiple colonization by no-C albicans spp +- ICU stay and risk factors (drug-interactions kind of patient pe transplantation peritonitis)

-Fluconazole 400-800 mg IVd If possible switching to oral therapy (400 mgd)

We must considered AF rapid broad spectrum and PKPD

optimized

Yes NO

-Anidulafungin 200 mg24 (d1)+100 mg d -Caspofungin 70 mg24 h (d1) + 50 mg d -Micafungina 150 mg24 hs - Amphotericin B-Lipidic Complex 3-5 mgkgd - Amphotericin B- Lipossomal 3 mgkgd - Voriconazol e iv 6 mgkg12h (d1) + 4 mgkg12h

EVEN POSSIBLE DE-ESCALATION

Zaragoza R Pemaacuten J J Invasive Fungal Infect 2007150-58

Antifungal de-escalation strategy

Initially a broad spectrum antitungal treatment is administrated until the agent of infection was identified

Echinocandins AMPHOTERICINS

Microbiogical data

Patientacutes physician criteria

Maintenance of broad spectrum combination

DT Switching to a narrow spectrum

Guery ICM2008

Candidemia pacientes no-neutropenicos De-escalation IDSA 2008

De-escalation even it`s possible (I-A)

Targeted Treatment of Candidaemia

Echinocandins

Compound SoR QoE Reference Comment

Anidulafungin

200100

A I Reboli NEJM 2007 bull Broad spectrum

bull Resistance rare

bull Fungicidal

bull Local epidemiology

bull C parapsilosis C krusei

bull Safety profile

bull Less drug-drug interactions

than caspofungin

Caspofungin

7050

A I Mora-Duarte NEJM 2002

Pappas CID 2007

bull Largely as above

Micafungin

100

A I Kuse Lancet 2007

Pappas CID 2007

bull Largely as above

bull Consider EMA warning label

Search for

Limits PreviewIndex History Clipboard Details

1 ORIGINAL

ARTICLE found

DE ESCALATION THERAPY AND CANDIDIASIS

0Pb8X13qPubMedpubmedGoSearch4DocSum200

Allaacute vamoshellip

A new schemehellip Invasive Candidiasis in ICU

The case for antifungal stewardship

bull httpwwwdisfrutalogratiscomcochesoporto2jpg

bull Introduction and definition

How to do it

bull Is de-escalation a real practise

bull Is an early broad spectrum

antifungal treatment needed

bull Do we need it Fluconazole

bull Which situations

bull NEVER

bull SOMETIMES

bull ALWAYS

bull When can we step down

ndash If case of proven IC

ndash If IC are not proven

bull Take home messages

Antimicrobial optimization strategies in ICU

GuidelinesProtocols

Restricting the hospital formulary

Scheduled changes in antibiotic

Combining antibiotic therapy

Antibiotic rotation

Area-specific antimicrobial therapy

Antimicrobial de-escalation

Kollef MH Crit Care 20015 189-95

INTRODUCTION Antimicrobial stewardship (AMS) has overwhelmingly focussed on antibiotics

while antifungal agents have been largely neglected despite the few published audits of antifungal drug use demonstrating clear deficiencies in prescibing behavior

Invasive fungal diseases (IFDs) have a lower institutional incidence relative to infections caused by multiresistant bacteria but their health and economic burden are substantial

Pharmacy costs inclusive of antifungal agents are a major determinant of IFD-attributable hospital cost High drug costs and the toxicities of antifungal agents are the principal rationale for AFS while antifungal resistance is an emerging but less prevalent issue

Nonculture-based tests may enhance AFS but refinement of both target populations and clinical pathways incorporating their use is required Performance indicators including structural process and outcome measures are integral for demonstrating the value of AFS programmes

Ananda-Rajah MR Slavin MA Thursky KT

Curr Opin Infect Dis 2012 Feb25(1)107-15

De-escalation of antibiotic therapy Concept

ldquoCould be considered as a strategy to balance the need to provide adequate initial antibiotic treatment of high risk patients with the avoidance of unnecessary antibiotic utilization which promotes resistancerdquo

Inadequate empirical antibitibic therapy and ICU-Bacteremia

6229

0

50

100

I EAT NO I EAT

I nhospital

Mortality

Ibrahim et al Chest 2000 118 146-155

N= 492 Candida spp VRE meticilin resistant S aureus CNS Pseudomonas aeruginosa

IEAT= 299

plt 0001

Inadequate empirical antibitibic therapy and ICU-Bacteremia

30235

0

10

20

30

I EAT NO-I EAT Related

mortality

N= 166 CNS Acinetobacter baumannii Pseudomonas aeruginosa Candida spp

Zaragoza R et al Clin Microbiol Infect 2003 May 9(5)412-418

IEAT= 235

pgt005

APPROACH TO ANTIFUNGAL TREATMENT

Pre-emptive and Empirical Therapy ICCd

iquestPrevious azol`s use +- clinical unstable (MOF severe sepsis) +- suspected or previous infection by C krusei o C glabrata +- multiple colonization by no-C albicans spp +- ICU stay and risk factors (drug-interactions kind of patient pe transplantation peritonitis)

-Fluconazole 400-800 mg IVd If possible switching to oral therapy (400 mgd)

We must considered AF rapid broad spectrum and PKPD

optimized

Yes NO

-Anidulafungin 200 mg24 (d1)+100 mg d -Caspofungin 70 mg24 h (d1) + 50 mg d -Micafungina 150 mg24 hs - Amphotericin B-Lipidic Complex 3-5 mgkgd - Amphotericin B- Lipossomal 3 mgkgd - Voriconazol e iv 6 mgkg12h (d1) + 4 mgkg12h

EVEN POSSIBLE DE-ESCALATION

Zaragoza R Pemaacuten J J Invasive Fungal Infect 2007150-58

Antifungal de-escalation strategy

Initially a broad spectrum antitungal treatment is administrated until the agent of infection was identified

Echinocandins AMPHOTERICINS

Microbiogical data

Patientacutes physician criteria

Maintenance of broad spectrum combination

DT Switching to a narrow spectrum

Guery ICM2008

Candidemia pacientes no-neutropenicos De-escalation IDSA 2008

De-escalation even it`s possible (I-A)

Targeted Treatment of Candidaemia

Echinocandins

Compound SoR QoE Reference Comment

Anidulafungin

200100

A I Reboli NEJM 2007 bull Broad spectrum

bull Resistance rare

bull Fungicidal

bull Local epidemiology

bull C parapsilosis C krusei

bull Safety profile

bull Less drug-drug interactions

than caspofungin

Caspofungin

7050

A I Mora-Duarte NEJM 2002

Pappas CID 2007

bull Largely as above

Micafungin

100

A I Kuse Lancet 2007

Pappas CID 2007

bull Largely as above

bull Consider EMA warning label

Search for

Limits PreviewIndex History Clipboard Details

1 ORIGINAL

ARTICLE found

DE ESCALATION THERAPY AND CANDIDIASIS

0Pb8X13qPubMedpubmedGoSearch4DocSum200

A new schemehellip Invasive Candidiasis in ICU

The case for antifungal stewardship

bull httpwwwdisfrutalogratiscomcochesoporto2jpg

bull Introduction and definition

How to do it

bull Is de-escalation a real practise

bull Is an early broad spectrum

antifungal treatment needed

bull Do we need it Fluconazole

bull Which situations

bull NEVER

bull SOMETIMES

bull ALWAYS

bull When can we step down

ndash If case of proven IC

ndash If IC are not proven

bull Take home messages

Antimicrobial optimization strategies in ICU

GuidelinesProtocols

Restricting the hospital formulary

Scheduled changes in antibiotic

Combining antibiotic therapy

Antibiotic rotation

Area-specific antimicrobial therapy

Antimicrobial de-escalation

Kollef MH Crit Care 20015 189-95

INTRODUCTION Antimicrobial stewardship (AMS) has overwhelmingly focussed on antibiotics

while antifungal agents have been largely neglected despite the few published audits of antifungal drug use demonstrating clear deficiencies in prescibing behavior

Invasive fungal diseases (IFDs) have a lower institutional incidence relative to infections caused by multiresistant bacteria but their health and economic burden are substantial

Pharmacy costs inclusive of antifungal agents are a major determinant of IFD-attributable hospital cost High drug costs and the toxicities of antifungal agents are the principal rationale for AFS while antifungal resistance is an emerging but less prevalent issue

Nonculture-based tests may enhance AFS but refinement of both target populations and clinical pathways incorporating their use is required Performance indicators including structural process and outcome measures are integral for demonstrating the value of AFS programmes

Ananda-Rajah MR Slavin MA Thursky KT

Curr Opin Infect Dis 2012 Feb25(1)107-15

De-escalation of antibiotic therapy Concept

ldquoCould be considered as a strategy to balance the need to provide adequate initial antibiotic treatment of high risk patients with the avoidance of unnecessary antibiotic utilization which promotes resistancerdquo

Inadequate empirical antibitibic therapy and ICU-Bacteremia

6229

0

50

100

I EAT NO I EAT

I nhospital

Mortality

Ibrahim et al Chest 2000 118 146-155

N= 492 Candida spp VRE meticilin resistant S aureus CNS Pseudomonas aeruginosa

IEAT= 299

plt 0001

Inadequate empirical antibitibic therapy and ICU-Bacteremia

30235

0

10

20

30

I EAT NO-I EAT Related

mortality

N= 166 CNS Acinetobacter baumannii Pseudomonas aeruginosa Candida spp

Zaragoza R et al Clin Microbiol Infect 2003 May 9(5)412-418

IEAT= 235

pgt005

APPROACH TO ANTIFUNGAL TREATMENT

Pre-emptive and Empirical Therapy ICCd

iquestPrevious azol`s use +- clinical unstable (MOF severe sepsis) +- suspected or previous infection by C krusei o C glabrata +- multiple colonization by no-C albicans spp +- ICU stay and risk factors (drug-interactions kind of patient pe transplantation peritonitis)

-Fluconazole 400-800 mg IVd If possible switching to oral therapy (400 mgd)

We must considered AF rapid broad spectrum and PKPD

optimized

Yes NO

-Anidulafungin 200 mg24 (d1)+100 mg d -Caspofungin 70 mg24 h (d1) + 50 mg d -Micafungina 150 mg24 hs - Amphotericin B-Lipidic Complex 3-5 mgkgd - Amphotericin B- Lipossomal 3 mgkgd - Voriconazol e iv 6 mgkg12h (d1) + 4 mgkg12h

EVEN POSSIBLE DE-ESCALATION

Zaragoza R Pemaacuten J J Invasive Fungal Infect 2007150-58

Antifungal de-escalation strategy

Initially a broad spectrum antitungal treatment is administrated until the agent of infection was identified

Echinocandins AMPHOTERICINS

Microbiogical data

Patientacutes physician criteria

Maintenance of broad spectrum combination

DT Switching to a narrow spectrum

Guery ICM2008

Candidemia pacientes no-neutropenicos De-escalation IDSA 2008

De-escalation even it`s possible (I-A)

Targeted Treatment of Candidaemia

Echinocandins

Compound SoR QoE Reference Comment

Anidulafungin

200100

A I Reboli NEJM 2007 bull Broad spectrum

bull Resistance rare

bull Fungicidal

bull Local epidemiology

bull C parapsilosis C krusei

bull Safety profile

bull Less drug-drug interactions

than caspofungin

Caspofungin

7050

A I Mora-Duarte NEJM 2002

Pappas CID 2007

bull Largely as above

Micafungin

100

A I Kuse Lancet 2007

Pappas CID 2007

bull Largely as above

bull Consider EMA warning label

Search for

Limits PreviewIndex History Clipboard Details

1 ORIGINAL

ARTICLE found

DE ESCALATION THERAPY AND CANDIDIASIS

0Pb8X13qPubMedpubmedGoSearch4DocSum200

Antimicrobial optimization strategies in ICU

GuidelinesProtocols

Restricting the hospital formulary

Scheduled changes in antibiotic

Combining antibiotic therapy

Antibiotic rotation

Area-specific antimicrobial therapy

Antimicrobial de-escalation

Kollef MH Crit Care 20015 189-95

INTRODUCTION Antimicrobial stewardship (AMS) has overwhelmingly focussed on antibiotics

while antifungal agents have been largely neglected despite the few published audits of antifungal drug use demonstrating clear deficiencies in prescibing behavior

Invasive fungal diseases (IFDs) have a lower institutional incidence relative to infections caused by multiresistant bacteria but their health and economic burden are substantial

Pharmacy costs inclusive of antifungal agents are a major determinant of IFD-attributable hospital cost High drug costs and the toxicities of antifungal agents are the principal rationale for AFS while antifungal resistance is an emerging but less prevalent issue

Nonculture-based tests may enhance AFS but refinement of both target populations and clinical pathways incorporating their use is required Performance indicators including structural process and outcome measures are integral for demonstrating the value of AFS programmes

Ananda-Rajah MR Slavin MA Thursky KT

Curr Opin Infect Dis 2012 Feb25(1)107-15

De-escalation of antibiotic therapy Concept

ldquoCould be considered as a strategy to balance the need to provide adequate initial antibiotic treatment of high risk patients with the avoidance of unnecessary antibiotic utilization which promotes resistancerdquo

Inadequate empirical antibitibic therapy and ICU-Bacteremia

6229

0

50

100

I EAT NO I EAT

I nhospital

Mortality

Ibrahim et al Chest 2000 118 146-155

N= 492 Candida spp VRE meticilin resistant S aureus CNS Pseudomonas aeruginosa

IEAT= 299

plt 0001

Inadequate empirical antibitibic therapy and ICU-Bacteremia

30235

0

10

20

30

I EAT NO-I EAT Related

mortality

N= 166 CNS Acinetobacter baumannii Pseudomonas aeruginosa Candida spp

Zaragoza R et al Clin Microbiol Infect 2003 May 9(5)412-418

IEAT= 235

pgt005

APPROACH TO ANTIFUNGAL TREATMENT

Pre-emptive and Empirical Therapy ICCd

iquestPrevious azol`s use +- clinical unstable (MOF severe sepsis) +- suspected or previous infection by C krusei o C glabrata +- multiple colonization by no-C albicans spp +- ICU stay and risk factors (drug-interactions kind of patient pe transplantation peritonitis)

-Fluconazole 400-800 mg IVd If possible switching to oral therapy (400 mgd)

We must considered AF rapid broad spectrum and PKPD

optimized

Yes NO

-Anidulafungin 200 mg24 (d1)+100 mg d -Caspofungin 70 mg24 h (d1) + 50 mg d -Micafungina 150 mg24 hs - Amphotericin B-Lipidic Complex 3-5 mgkgd - Amphotericin B- Lipossomal 3 mgkgd - Voriconazol e iv 6 mgkg12h (d1) + 4 mgkg12h

EVEN POSSIBLE DE-ESCALATION

Zaragoza R Pemaacuten J J Invasive Fungal Infect 2007150-58

Antifungal de-escalation strategy

Initially a broad spectrum antitungal treatment is administrated until the agent of infection was identified

Echinocandins AMPHOTERICINS

Microbiogical data

Patientacutes physician criteria

Maintenance of broad spectrum combination

DT Switching to a narrow spectrum

Guery ICM2008

Candidemia pacientes no-neutropenicos De-escalation IDSA 2008

De-escalation even it`s possible (I-A)

Targeted Treatment of Candidaemia

Echinocandins

Compound SoR QoE Reference Comment

Anidulafungin

200100

A I Reboli NEJM 2007 bull Broad spectrum

bull Resistance rare

bull Fungicidal

bull Local epidemiology

bull C parapsilosis C krusei

bull Safety profile

bull Less drug-drug interactions

than caspofungin

Caspofungin

7050

A I Mora-Duarte NEJM 2002

Pappas CID 2007

bull Largely as above

Micafungin

100

A I Kuse Lancet 2007

Pappas CID 2007

bull Largely as above

bull Consider EMA warning label

Search for

Limits PreviewIndex History Clipboard Details

1 ORIGINAL

ARTICLE found

DE ESCALATION THERAPY AND CANDIDIASIS

0Pb8X13qPubMedpubmedGoSearch4DocSum200

INTRODUCTION Antimicrobial stewardship (AMS) has overwhelmingly focussed on antibiotics

while antifungal agents have been largely neglected despite the few published audits of antifungal drug use demonstrating clear deficiencies in prescibing behavior

Invasive fungal diseases (IFDs) have a lower institutional incidence relative to infections caused by multiresistant bacteria but their health and economic burden are substantial

Pharmacy costs inclusive of antifungal agents are a major determinant of IFD-attributable hospital cost High drug costs and the toxicities of antifungal agents are the principal rationale for AFS while antifungal resistance is an emerging but less prevalent issue

Nonculture-based tests may enhance AFS but refinement of both target populations and clinical pathways incorporating their use is required Performance indicators including structural process and outcome measures are integral for demonstrating the value of AFS programmes

Ananda-Rajah MR Slavin MA Thursky KT

Curr Opin Infect Dis 2012 Feb25(1)107-15

De-escalation of antibiotic therapy Concept

ldquoCould be considered as a strategy to balance the need to provide adequate initial antibiotic treatment of high risk patients with the avoidance of unnecessary antibiotic utilization which promotes resistancerdquo

Inadequate empirical antibitibic therapy and ICU-Bacteremia

6229

0

50

100

I EAT NO I EAT

I nhospital

Mortality

Ibrahim et al Chest 2000 118 146-155

N= 492 Candida spp VRE meticilin resistant S aureus CNS Pseudomonas aeruginosa

IEAT= 299

plt 0001

Inadequate empirical antibitibic therapy and ICU-Bacteremia

30235

0

10

20

30

I EAT NO-I EAT Related

mortality

N= 166 CNS Acinetobacter baumannii Pseudomonas aeruginosa Candida spp

Zaragoza R et al Clin Microbiol Infect 2003 May 9(5)412-418

IEAT= 235

pgt005

APPROACH TO ANTIFUNGAL TREATMENT

Pre-emptive and Empirical Therapy ICCd

iquestPrevious azol`s use +- clinical unstable (MOF severe sepsis) +- suspected or previous infection by C krusei o C glabrata +- multiple colonization by no-C albicans spp +- ICU stay and risk factors (drug-interactions kind of patient pe transplantation peritonitis)

-Fluconazole 400-800 mg IVd If possible switching to oral therapy (400 mgd)

We must considered AF rapid broad spectrum and PKPD

optimized

Yes NO

-Anidulafungin 200 mg24 (d1)+100 mg d -Caspofungin 70 mg24 h (d1) + 50 mg d -Micafungina 150 mg24 hs - Amphotericin B-Lipidic Complex 3-5 mgkgd - Amphotericin B- Lipossomal 3 mgkgd - Voriconazol e iv 6 mgkg12h (d1) + 4 mgkg12h

EVEN POSSIBLE DE-ESCALATION

Zaragoza R Pemaacuten J J Invasive Fungal Infect 2007150-58

Antifungal de-escalation strategy

Initially a broad spectrum antitungal treatment is administrated until the agent of infection was identified

Echinocandins AMPHOTERICINS

Microbiogical data

Patientacutes physician criteria

Maintenance of broad spectrum combination

DT Switching to a narrow spectrum

Guery ICM2008

Candidemia pacientes no-neutropenicos De-escalation IDSA 2008

De-escalation even it`s possible (I-A)

Targeted Treatment of Candidaemia

Echinocandins

Compound SoR QoE Reference Comment

Anidulafungin

200100

A I Reboli NEJM 2007 bull Broad spectrum

bull Resistance rare

bull Fungicidal

bull Local epidemiology

bull C parapsilosis C krusei

bull Safety profile

bull Less drug-drug interactions

than caspofungin

Caspofungin

7050

A I Mora-Duarte NEJM 2002

Pappas CID 2007

bull Largely as above

Micafungin

100

A I Kuse Lancet 2007

Pappas CID 2007

bull Largely as above

bull Consider EMA warning label

Search for

Limits PreviewIndex History Clipboard Details

1 ORIGINAL

ARTICLE found

DE ESCALATION THERAPY AND CANDIDIASIS

0Pb8X13qPubMedpubmedGoSearch4DocSum200

De-escalation of antibiotic therapy Concept

ldquoCould be considered as a strategy to balance the need to provide adequate initial antibiotic treatment of high risk patients with the avoidance of unnecessary antibiotic utilization which promotes resistancerdquo

Inadequate empirical antibitibic therapy and ICU-Bacteremia

6229

0

50

100

I EAT NO I EAT

I nhospital

Mortality

Ibrahim et al Chest 2000 118 146-155

N= 492 Candida spp VRE meticilin resistant S aureus CNS Pseudomonas aeruginosa

IEAT= 299

plt 0001

Inadequate empirical antibitibic therapy and ICU-Bacteremia

30235

0

10

20

30

I EAT NO-I EAT Related

mortality

N= 166 CNS Acinetobacter baumannii Pseudomonas aeruginosa Candida spp

Zaragoza R et al Clin Microbiol Infect 2003 May 9(5)412-418

IEAT= 235

pgt005

APPROACH TO ANTIFUNGAL TREATMENT

Pre-emptive and Empirical Therapy ICCd

iquestPrevious azol`s use +- clinical unstable (MOF severe sepsis) +- suspected or previous infection by C krusei o C glabrata +- multiple colonization by no-C albicans spp +- ICU stay and risk factors (drug-interactions kind of patient pe transplantation peritonitis)

-Fluconazole 400-800 mg IVd If possible switching to oral therapy (400 mgd)

We must considered AF rapid broad spectrum and PKPD

optimized

Yes NO

-Anidulafungin 200 mg24 (d1)+100 mg d -Caspofungin 70 mg24 h (d1) + 50 mg d -Micafungina 150 mg24 hs - Amphotericin B-Lipidic Complex 3-5 mgkgd - Amphotericin B- Lipossomal 3 mgkgd - Voriconazol e iv 6 mgkg12h (d1) + 4 mgkg12h

EVEN POSSIBLE DE-ESCALATION

Zaragoza R Pemaacuten J J Invasive Fungal Infect 2007150-58

Antifungal de-escalation strategy

Initially a broad spectrum antitungal treatment is administrated until the agent of infection was identified

Echinocandins AMPHOTERICINS

Microbiogical data

Patientacutes physician criteria

Maintenance of broad spectrum combination

DT Switching to a narrow spectrum

Guery ICM2008

Candidemia pacientes no-neutropenicos De-escalation IDSA 2008

De-escalation even it`s possible (I-A)

Targeted Treatment of Candidaemia

Echinocandins

Compound SoR QoE Reference Comment

Anidulafungin

200100

A I Reboli NEJM 2007 bull Broad spectrum

bull Resistance rare

bull Fungicidal

bull Local epidemiology

bull C parapsilosis C krusei

bull Safety profile

bull Less drug-drug interactions

than caspofungin

Caspofungin

7050

A I Mora-Duarte NEJM 2002

Pappas CID 2007

bull Largely as above

Micafungin

100

A I Kuse Lancet 2007

Pappas CID 2007

bull Largely as above

bull Consider EMA warning label

Search for

Limits PreviewIndex History Clipboard Details

1 ORIGINAL

ARTICLE found

DE ESCALATION THERAPY AND CANDIDIASIS

0Pb8X13qPubMedpubmedGoSearch4DocSum200

Inadequate empirical antibitibic therapy and ICU-Bacteremia

6229

0

50

100

I EAT NO I EAT

I nhospital

Mortality

Ibrahim et al Chest 2000 118 146-155

N= 492 Candida spp VRE meticilin resistant S aureus CNS Pseudomonas aeruginosa

IEAT= 299

plt 0001

Inadequate empirical antibitibic therapy and ICU-Bacteremia

30235

0

10

20

30

I EAT NO-I EAT Related

mortality

N= 166 CNS Acinetobacter baumannii Pseudomonas aeruginosa Candida spp

Zaragoza R et al Clin Microbiol Infect 2003 May 9(5)412-418

IEAT= 235

pgt005

APPROACH TO ANTIFUNGAL TREATMENT

Pre-emptive and Empirical Therapy ICCd

iquestPrevious azol`s use +- clinical unstable (MOF severe sepsis) +- suspected or previous infection by C krusei o C glabrata +- multiple colonization by no-C albicans spp +- ICU stay and risk factors (drug-interactions kind of patient pe transplantation peritonitis)

-Fluconazole 400-800 mg IVd If possible switching to oral therapy (400 mgd)

We must considered AF rapid broad spectrum and PKPD

optimized

Yes NO

-Anidulafungin 200 mg24 (d1)+100 mg d -Caspofungin 70 mg24 h (d1) + 50 mg d -Micafungina 150 mg24 hs - Amphotericin B-Lipidic Complex 3-5 mgkgd - Amphotericin B- Lipossomal 3 mgkgd - Voriconazol e iv 6 mgkg12h (d1) + 4 mgkg12h

EVEN POSSIBLE DE-ESCALATION

Zaragoza R Pemaacuten J J Invasive Fungal Infect 2007150-58

Antifungal de-escalation strategy

Initially a broad spectrum antitungal treatment is administrated until the agent of infection was identified

Echinocandins AMPHOTERICINS

Microbiogical data

Patientacutes physician criteria

Maintenance of broad spectrum combination

DT Switching to a narrow spectrum

Guery ICM2008

Candidemia pacientes no-neutropenicos De-escalation IDSA 2008

De-escalation even it`s possible (I-A)

Targeted Treatment of Candidaemia

Echinocandins

Compound SoR QoE Reference Comment

Anidulafungin

200100

A I Reboli NEJM 2007 bull Broad spectrum

bull Resistance rare

bull Fungicidal

bull Local epidemiology

bull C parapsilosis C krusei

bull Safety profile

bull Less drug-drug interactions

than caspofungin

Caspofungin

7050

A I Mora-Duarte NEJM 2002

Pappas CID 2007

bull Largely as above

Micafungin

100

A I Kuse Lancet 2007

Pappas CID 2007

bull Largely as above

bull Consider EMA warning label

Search for

Limits PreviewIndex History Clipboard Details

1 ORIGINAL

ARTICLE found

DE ESCALATION THERAPY AND CANDIDIASIS

0Pb8X13qPubMedpubmedGoSearch4DocSum200

Inadequate empirical antibitibic therapy and ICU-Bacteremia

30235

0

10

20

30

I EAT NO-I EAT Related

mortality

N= 166 CNS Acinetobacter baumannii Pseudomonas aeruginosa Candida spp

Zaragoza R et al Clin Microbiol Infect 2003 May 9(5)412-418

IEAT= 235

pgt005

APPROACH TO ANTIFUNGAL TREATMENT

Pre-emptive and Empirical Therapy ICCd

iquestPrevious azol`s use +- clinical unstable (MOF severe sepsis) +- suspected or previous infection by C krusei o C glabrata +- multiple colonization by no-C albicans spp +- ICU stay and risk factors (drug-interactions kind of patient pe transplantation peritonitis)

-Fluconazole 400-800 mg IVd If possible switching to oral therapy (400 mgd)

We must considered AF rapid broad spectrum and PKPD

optimized

Yes NO

-Anidulafungin 200 mg24 (d1)+100 mg d -Caspofungin 70 mg24 h (d1) + 50 mg d -Micafungina 150 mg24 hs - Amphotericin B-Lipidic Complex 3-5 mgkgd - Amphotericin B- Lipossomal 3 mgkgd - Voriconazol e iv 6 mgkg12h (d1) + 4 mgkg12h

EVEN POSSIBLE DE-ESCALATION

Zaragoza R Pemaacuten J J Invasive Fungal Infect 2007150-58

Antifungal de-escalation strategy

Initially a broad spectrum antitungal treatment is administrated until the agent of infection was identified

Echinocandins AMPHOTERICINS

Microbiogical data

Patientacutes physician criteria

Maintenance of broad spectrum combination

DT Switching to a narrow spectrum

Guery ICM2008

Candidemia pacientes no-neutropenicos De-escalation IDSA 2008

De-escalation even it`s possible (I-A)

Targeted Treatment of Candidaemia

Echinocandins

Compound SoR QoE Reference Comment

Anidulafungin

200100

A I Reboli NEJM 2007 bull Broad spectrum

bull Resistance rare

bull Fungicidal

bull Local epidemiology

bull C parapsilosis C krusei

bull Safety profile

bull Less drug-drug interactions

than caspofungin

Caspofungin

7050

A I Mora-Duarte NEJM 2002

Pappas CID 2007

bull Largely as above

Micafungin

100

A I Kuse Lancet 2007

Pappas CID 2007

bull Largely as above

bull Consider EMA warning label

Search for

Limits PreviewIndex History Clipboard Details

1 ORIGINAL

ARTICLE found

DE ESCALATION THERAPY AND CANDIDIASIS

0Pb8X13qPubMedpubmedGoSearch4DocSum200

APPROACH TO ANTIFUNGAL TREATMENT

Pre-emptive and Empirical Therapy ICCd

iquestPrevious azol`s use +- clinical unstable (MOF severe sepsis) +- suspected or previous infection by C krusei o C glabrata +- multiple colonization by no-C albicans spp +- ICU stay and risk factors (drug-interactions kind of patient pe transplantation peritonitis)

-Fluconazole 400-800 mg IVd If possible switching to oral therapy (400 mgd)

We must considered AF rapid broad spectrum and PKPD

optimized

Yes NO

-Anidulafungin 200 mg24 (d1)+100 mg d -Caspofungin 70 mg24 h (d1) + 50 mg d -Micafungina 150 mg24 hs - Amphotericin B-Lipidic Complex 3-5 mgkgd - Amphotericin B- Lipossomal 3 mgkgd - Voriconazol e iv 6 mgkg12h (d1) + 4 mgkg12h

EVEN POSSIBLE DE-ESCALATION

Zaragoza R Pemaacuten J J Invasive Fungal Infect 2007150-58

Antifungal de-escalation strategy

Initially a broad spectrum antitungal treatment is administrated until the agent of infection was identified

Echinocandins AMPHOTERICINS

Microbiogical data

Patientacutes physician criteria

Maintenance of broad spectrum combination

DT Switching to a narrow spectrum

Guery ICM2008

Candidemia pacientes no-neutropenicos De-escalation IDSA 2008

De-escalation even it`s possible (I-A)

Targeted Treatment of Candidaemia

Echinocandins

Compound SoR QoE Reference Comment

Anidulafungin

200100

A I Reboli NEJM 2007 bull Broad spectrum

bull Resistance rare

bull Fungicidal

bull Local epidemiology

bull C parapsilosis C krusei

bull Safety profile

bull Less drug-drug interactions

than caspofungin

Caspofungin

7050

A I Mora-Duarte NEJM 2002

Pappas CID 2007

bull Largely as above

Micafungin

100

A I Kuse Lancet 2007

Pappas CID 2007

bull Largely as above

bull Consider EMA warning label

Search for

Limits PreviewIndex History Clipboard Details

1 ORIGINAL

ARTICLE found

DE ESCALATION THERAPY AND CANDIDIASIS

0Pb8X13qPubMedpubmedGoSearch4DocSum200

Antifungal de-escalation strategy

Initially a broad spectrum antitungal treatment is administrated until the agent of infection was identified

Echinocandins AMPHOTERICINS

Microbiogical data

Patientacutes physician criteria

Maintenance of broad spectrum combination

DT Switching to a narrow spectrum

Guery ICM2008

Candidemia pacientes no-neutropenicos De-escalation IDSA 2008

De-escalation even it`s possible (I-A)

Targeted Treatment of Candidaemia

Echinocandins

Compound SoR QoE Reference Comment

Anidulafungin

200100

A I Reboli NEJM 2007 bull Broad spectrum

bull Resistance rare

bull Fungicidal

bull Local epidemiology

bull C parapsilosis C krusei

bull Safety profile

bull Less drug-drug interactions

than caspofungin

Caspofungin

7050

A I Mora-Duarte NEJM 2002

Pappas CID 2007

bull Largely as above

Micafungin

100

A I Kuse Lancet 2007

Pappas CID 2007

bull Largely as above

bull Consider EMA warning label

Search for

Limits PreviewIndex History Clipboard Details

1 ORIGINAL

ARTICLE found

DE ESCALATION THERAPY AND CANDIDIASIS

0Pb8X13qPubMedpubmedGoSearch4DocSum200

Guery ICM2008

Candidemia pacientes no-neutropenicos De-escalation IDSA 2008

De-escalation even it`s possible (I-A)

Targeted Treatment of Candidaemia

Echinocandins

Compound SoR QoE Reference Comment

Anidulafungin

200100

A I Reboli NEJM 2007 bull Broad spectrum

bull Resistance rare

bull Fungicidal

bull Local epidemiology

bull C parapsilosis C krusei

bull Safety profile

bull Less drug-drug interactions

than caspofungin

Caspofungin

7050

A I Mora-Duarte NEJM 2002

Pappas CID 2007

bull Largely as above

Micafungin

100

A I Kuse Lancet 2007

Pappas CID 2007

bull Largely as above

bull Consider EMA warning label

Search for

Limits PreviewIndex History Clipboard Details

1 ORIGINAL

ARTICLE found

DE ESCALATION THERAPY AND CANDIDIASIS

0Pb8X13qPubMedpubmedGoSearch4DocSum200

Candidemia pacientes no-neutropenicos De-escalation IDSA 2008

De-escalation even it`s possible (I-A)

Targeted Treatment of Candidaemia

Echinocandins

Compound SoR QoE Reference Comment

Anidulafungin

200100

A I Reboli NEJM 2007 bull Broad spectrum

bull Resistance rare

bull Fungicidal

bull Local epidemiology

bull C parapsilosis C krusei

bull Safety profile

bull Less drug-drug interactions

than caspofungin

Caspofungin

7050

A I Mora-Duarte NEJM 2002

Pappas CID 2007

bull Largely as above

Micafungin

100

A I Kuse Lancet 2007

Pappas CID 2007

bull Largely as above

bull Consider EMA warning label

Search for

Limits PreviewIndex History Clipboard Details

1 ORIGINAL

ARTICLE found

DE ESCALATION THERAPY AND CANDIDIASIS

0Pb8X13qPubMedpubmedGoSearch4DocSum200

Targeted Treatment of Candidaemia

Echinocandins

Compound SoR QoE Reference Comment

Anidulafungin

200100

A I Reboli NEJM 2007 bull Broad spectrum

bull Resistance rare

bull Fungicidal

bull Local epidemiology

bull C parapsilosis C krusei

bull Safety profile

bull Less drug-drug interactions

than caspofungin

Caspofungin

7050

A I Mora-Duarte NEJM 2002

Pappas CID 2007

bull Largely as above

Micafungin

100

A I Kuse Lancet 2007

Pappas CID 2007

bull Largely as above

bull Consider EMA warning label

Search for

Limits PreviewIndex History Clipboard Details

1 ORIGINAL

ARTICLE found

DE ESCALATION THERAPY AND CANDIDIASIS

0Pb8X13qPubMedpubmedGoSearch4DocSum200

Search for

Limits PreviewIndex History Clipboard Details

1 ORIGINAL

ARTICLE found

DE ESCALATION THERAPY AND CANDIDIASIS

0Pb8X13qPubMedpubmedGoSearch4DocSum200

DESESCALADA ARTIacuteCULO

What did happen in tle last trials

WAY OF DE-ESCALATION

ICE STUDY Patients could be switched

to oral voriconazole or fluconazole at the discretion of the investigator after a minimum of 10 daysrsquo anidulafungin treatment if they had 2 subsequent negative blood cultures and resolution of CIC signs and symptoms

REBOLI STUDY All patients could

receive oralfluconazole (400 mg daily) at the investigatorsrsquodiscretion after at least 10 days of intravenoustherapy if the patients were able to tolerate oralmedication if they had been afebrile for at least24 hours if the most recent blood culture wasnegative for candida species and if there wasclinical improvement

IMPLEMENTATION

ICE STUDY53 patients were switched to

an oral azole 41 to fluconazole (mean duration 117 days range 3-44) and 12 to voriconazole (mean duration 112 days range 5-20)

REBOLI STUDY 33 patients FROM

EACH GROUP were switched to an oral FLUCONAZOLE

34

26-28

Reboli A et al NEJM 2007

Ruhnke M et al CMI in press

Is early treatment needed for Invasive Candidiasis in critically ill patients

Yeshellipof coursehelliphellip

Difficulties in Establishing a

Diagnosis for Candidemia

No disease CulturesAntigen Signs and

symptoms

Cultures

histopathology Sequelae

Prophylaxis Preemptive Empirical

Crude Mortality

40

Treatment Morbidity

Mortality

Delaying the Empiric Treatment of Candidemia An Independent Risk Factor for Hospital Mortality

lt12 lt 24 gt24 gt48

0

5

10

15

20

25

30

35

H

ospital M

ort

alit

y

Delay in Start of Antifungal

Therapy (days)

Variable OR 95 CI P

APACHE II 124 (118-131) lt0001

Prior antibiotics 405 (214-765) 0028

Delay in antifungal 209 (153-284) 0018

therapy

Multivariate analysis of independent risk

factors for hospital mortality

Morrell et al Antimicrob Agent Chemother 2005493640

Garey KW Clin Infect Dis 2006 4325-31

The Effect of Time to Antifungal Therapy on Mortality in Candidemia associated Septic Shock

Patel GP et al Am J Therapeutics 2009

Septic shock developed in 23 (31 of 135) patients with CBSI

In-hospital mortality was 68

Appropriate antifungal therapy was

administered to 24 patients 15 (63)

of these patients died

Patients who received appropriate

antifungal therapy within 15 hours of

collecting the first positive Candida

blood culture had improved survival

(P = 003)

Caspo velocidad

Relationship between ldquoCandida scorerdquo and risk for developing IC in surgical patients

C Leon et al Crit Care Med 2009 371624 ndash1633

0

5

10

15

20

25

30

35

CSlt3 CSgt3 CS=3

Abdominal surgery

No abdominalsurgery

P lt005

IC in surgical patients according CS

NCMT NCMT

Non-culture microbiological tools [(13)-

b-D-glucan Candida albicans germ tube

antibodies or PCR

Mycoses 2010

Fluconazole To be or not to be

Jacobs et al CCM 312003

71 septic shock patients (Pneumonia=37 y Intrabadominal=34) Randomized (32 pts) 200 mg fluconazole iv vs (39 pts) placebo

Epidemiological trends in nosocomial

candidemia in intensive care

Bassetti M et al BMC Infectious Diseases 2006680

Candidemias in ICU

HUDP 1996-2007

5

95

Candidemias Bacteriemias

48

23

10

19

Candida albicans Candida glabrata Candida parapsilopsis Otras

N =397 N = 31

Mortality in C no albicans episodes

gt Calbicans (125 vs 466 p= 003)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

57

8

8

17 5

5

Candida albicans Candida glabrata Candida parapsilopsis

Candida krusei Ctropicalis Otras

N =271

Leroy O et al Crit Care Med 2009

Reduced susceptibility to fluconazole 171

Desescalated 371

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

What did happen in tle last trials

WAY OF DE-ESCALATION

ICE STUDY Patients could be switched

to oral voriconazole or fluconazole at the discretion of the investigator after a minimum of 10 daysrsquo anidulafungin treatment if they had 2 subsequent negative blood cultures and resolution of CIC signs and symptoms

REBOLI STUDY All patients could

receive oralfluconazole (400 mg daily) at the investigatorsrsquodiscretion after at least 10 days of intravenoustherapy if the patients were able to tolerate oralmedication if they had been afebrile for at least24 hours if the most recent blood culture wasnegative for candida species and if there wasclinical improvement

IMPLEMENTATION

ICE STUDY53 patients were switched to

an oral azole 41 to fluconazole (mean duration 117 days range 3-44) and 12 to voriconazole (mean duration 112 days range 5-20)

REBOLI STUDY 33 patients FROM

EACH GROUP were switched to an oral FLUCONAZOLE

34

26-28

Reboli A et al NEJM 2007

Ruhnke M et al CMI in press

Is early treatment needed for Invasive Candidiasis in critically ill patients

Yeshellipof coursehelliphellip

Difficulties in Establishing a

Diagnosis for Candidemia

No disease CulturesAntigen Signs and

symptoms

Cultures

histopathology Sequelae

Prophylaxis Preemptive Empirical

Crude Mortality

40

Treatment Morbidity

Mortality

Delaying the Empiric Treatment of Candidemia An Independent Risk Factor for Hospital Mortality

lt12 lt 24 gt24 gt48

0

5

10

15

20

25

30

35

H

ospital M

ort

alit

y

Delay in Start of Antifungal

Therapy (days)

Variable OR 95 CI P

APACHE II 124 (118-131) lt0001

Prior antibiotics 405 (214-765) 0028

Delay in antifungal 209 (153-284) 0018

therapy

Multivariate analysis of independent risk

factors for hospital mortality

Morrell et al Antimicrob Agent Chemother 2005493640

Garey KW Clin Infect Dis 2006 4325-31

The Effect of Time to Antifungal Therapy on Mortality in Candidemia associated Septic Shock

Patel GP et al Am J Therapeutics 2009

Septic shock developed in 23 (31 of 135) patients with CBSI

In-hospital mortality was 68

Appropriate antifungal therapy was

administered to 24 patients 15 (63)

of these patients died

Patients who received appropriate

antifungal therapy within 15 hours of

collecting the first positive Candida

blood culture had improved survival

(P = 003)

Caspo velocidad

Relationship between ldquoCandida scorerdquo and risk for developing IC in surgical patients

C Leon et al Crit Care Med 2009 371624 ndash1633

0

5

10

15

20

25

30

35

CSlt3 CSgt3 CS=3

Abdominal surgery

No abdominalsurgery

P lt005

IC in surgical patients according CS

NCMT NCMT

Non-culture microbiological tools [(13)-

b-D-glucan Candida albicans germ tube

antibodies or PCR

Mycoses 2010

Fluconazole To be or not to be

Jacobs et al CCM 312003

71 septic shock patients (Pneumonia=37 y Intrabadominal=34) Randomized (32 pts) 200 mg fluconazole iv vs (39 pts) placebo

Epidemiological trends in nosocomial

candidemia in intensive care

Bassetti M et al BMC Infectious Diseases 2006680

Candidemias in ICU

HUDP 1996-2007

5

95

Candidemias Bacteriemias

48

23

10

19

Candida albicans Candida glabrata Candida parapsilopsis Otras

N =397 N = 31

Mortality in C no albicans episodes

gt Calbicans (125 vs 466 p= 003)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

57

8

8

17 5

5

Candida albicans Candida glabrata Candida parapsilopsis

Candida krusei Ctropicalis Otras

N =271

Leroy O et al Crit Care Med 2009

Reduced susceptibility to fluconazole 171

Desescalated 371

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

Is early treatment needed for Invasive Candidiasis in critically ill patients

Yeshellipof coursehelliphellip

Difficulties in Establishing a

Diagnosis for Candidemia

No disease CulturesAntigen Signs and

symptoms

Cultures

histopathology Sequelae

Prophylaxis Preemptive Empirical

Crude Mortality

40

Treatment Morbidity

Mortality

Delaying the Empiric Treatment of Candidemia An Independent Risk Factor for Hospital Mortality

lt12 lt 24 gt24 gt48

0

5

10

15

20

25

30

35

H

ospital M

ort

alit

y

Delay in Start of Antifungal

Therapy (days)

Variable OR 95 CI P

APACHE II 124 (118-131) lt0001

Prior antibiotics 405 (214-765) 0028

Delay in antifungal 209 (153-284) 0018

therapy

Multivariate analysis of independent risk

factors for hospital mortality

Morrell et al Antimicrob Agent Chemother 2005493640

Garey KW Clin Infect Dis 2006 4325-31

The Effect of Time to Antifungal Therapy on Mortality in Candidemia associated Septic Shock

Patel GP et al Am J Therapeutics 2009

Septic shock developed in 23 (31 of 135) patients with CBSI

In-hospital mortality was 68

Appropriate antifungal therapy was

administered to 24 patients 15 (63)

of these patients died

Patients who received appropriate

antifungal therapy within 15 hours of

collecting the first positive Candida

blood culture had improved survival

(P = 003)

Caspo velocidad

Relationship between ldquoCandida scorerdquo and risk for developing IC in surgical patients

C Leon et al Crit Care Med 2009 371624 ndash1633

0

5

10

15

20

25

30

35

CSlt3 CSgt3 CS=3

Abdominal surgery

No abdominalsurgery

P lt005

IC in surgical patients according CS

NCMT NCMT

Non-culture microbiological tools [(13)-

b-D-glucan Candida albicans germ tube

antibodies or PCR

Mycoses 2010

Fluconazole To be or not to be

Jacobs et al CCM 312003

71 septic shock patients (Pneumonia=37 y Intrabadominal=34) Randomized (32 pts) 200 mg fluconazole iv vs (39 pts) placebo

Epidemiological trends in nosocomial

candidemia in intensive care

Bassetti M et al BMC Infectious Diseases 2006680

Candidemias in ICU

HUDP 1996-2007

5

95

Candidemias Bacteriemias

48

23

10

19

Candida albicans Candida glabrata Candida parapsilopsis Otras

N =397 N = 31

Mortality in C no albicans episodes

gt Calbicans (125 vs 466 p= 003)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

57

8

8

17 5

5

Candida albicans Candida glabrata Candida parapsilopsis

Candida krusei Ctropicalis Otras

N =271

Leroy O et al Crit Care Med 2009

Reduced susceptibility to fluconazole 171

Desescalated 371

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

Yeshellipof coursehelliphellip

Difficulties in Establishing a

Diagnosis for Candidemia

No disease CulturesAntigen Signs and

symptoms

Cultures

histopathology Sequelae

Prophylaxis Preemptive Empirical

Crude Mortality

40

Treatment Morbidity

Mortality

Delaying the Empiric Treatment of Candidemia An Independent Risk Factor for Hospital Mortality

lt12 lt 24 gt24 gt48

0

5

10

15

20

25

30

35

H

ospital M

ort

alit

y

Delay in Start of Antifungal

Therapy (days)

Variable OR 95 CI P

APACHE II 124 (118-131) lt0001

Prior antibiotics 405 (214-765) 0028

Delay in antifungal 209 (153-284) 0018

therapy

Multivariate analysis of independent risk

factors for hospital mortality

Morrell et al Antimicrob Agent Chemother 2005493640

Garey KW Clin Infect Dis 2006 4325-31

The Effect of Time to Antifungal Therapy on Mortality in Candidemia associated Septic Shock

Patel GP et al Am J Therapeutics 2009

Septic shock developed in 23 (31 of 135) patients with CBSI

In-hospital mortality was 68

Appropriate antifungal therapy was

administered to 24 patients 15 (63)

of these patients died

Patients who received appropriate

antifungal therapy within 15 hours of

collecting the first positive Candida

blood culture had improved survival

(P = 003)

Caspo velocidad

Relationship between ldquoCandida scorerdquo and risk for developing IC in surgical patients

C Leon et al Crit Care Med 2009 371624 ndash1633

0

5

10

15

20

25

30

35

CSlt3 CSgt3 CS=3

Abdominal surgery

No abdominalsurgery

P lt005

IC in surgical patients according CS

NCMT NCMT

Non-culture microbiological tools [(13)-

b-D-glucan Candida albicans germ tube

antibodies or PCR

Mycoses 2010

Fluconazole To be or not to be

Jacobs et al CCM 312003

71 septic shock patients (Pneumonia=37 y Intrabadominal=34) Randomized (32 pts) 200 mg fluconazole iv vs (39 pts) placebo

Epidemiological trends in nosocomial

candidemia in intensive care

Bassetti M et al BMC Infectious Diseases 2006680

Candidemias in ICU

HUDP 1996-2007

5

95

Candidemias Bacteriemias

48

23

10

19

Candida albicans Candida glabrata Candida parapsilopsis Otras

N =397 N = 31

Mortality in C no albicans episodes

gt Calbicans (125 vs 466 p= 003)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

57

8

8

17 5

5

Candida albicans Candida glabrata Candida parapsilopsis

Candida krusei Ctropicalis Otras

N =271

Leroy O et al Crit Care Med 2009

Reduced susceptibility to fluconazole 171

Desescalated 371

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

Difficulties in Establishing a

Diagnosis for Candidemia

No disease CulturesAntigen Signs and

symptoms

Cultures

histopathology Sequelae

Prophylaxis Preemptive Empirical

Crude Mortality

40

Treatment Morbidity

Mortality

Delaying the Empiric Treatment of Candidemia An Independent Risk Factor for Hospital Mortality

lt12 lt 24 gt24 gt48

0

5

10

15

20

25

30

35

H

ospital M

ort

alit

y

Delay in Start of Antifungal

Therapy (days)

Variable OR 95 CI P

APACHE II 124 (118-131) lt0001

Prior antibiotics 405 (214-765) 0028

Delay in antifungal 209 (153-284) 0018

therapy

Multivariate analysis of independent risk

factors for hospital mortality

Morrell et al Antimicrob Agent Chemother 2005493640

Garey KW Clin Infect Dis 2006 4325-31

The Effect of Time to Antifungal Therapy on Mortality in Candidemia associated Septic Shock

Patel GP et al Am J Therapeutics 2009

Septic shock developed in 23 (31 of 135) patients with CBSI

In-hospital mortality was 68

Appropriate antifungal therapy was

administered to 24 patients 15 (63)

of these patients died

Patients who received appropriate

antifungal therapy within 15 hours of

collecting the first positive Candida

blood culture had improved survival

(P = 003)

Caspo velocidad

Relationship between ldquoCandida scorerdquo and risk for developing IC in surgical patients

C Leon et al Crit Care Med 2009 371624 ndash1633

0

5

10

15

20

25

30

35

CSlt3 CSgt3 CS=3

Abdominal surgery

No abdominalsurgery

P lt005

IC in surgical patients according CS

NCMT NCMT

Non-culture microbiological tools [(13)-

b-D-glucan Candida albicans germ tube

antibodies or PCR

Mycoses 2010

Fluconazole To be or not to be

Jacobs et al CCM 312003

71 septic shock patients (Pneumonia=37 y Intrabadominal=34) Randomized (32 pts) 200 mg fluconazole iv vs (39 pts) placebo

Epidemiological trends in nosocomial

candidemia in intensive care

Bassetti M et al BMC Infectious Diseases 2006680

Candidemias in ICU

HUDP 1996-2007

5

95

Candidemias Bacteriemias

48

23

10

19

Candida albicans Candida glabrata Candida parapsilopsis Otras

N =397 N = 31

Mortality in C no albicans episodes

gt Calbicans (125 vs 466 p= 003)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

57

8

8

17 5

5

Candida albicans Candida glabrata Candida parapsilopsis

Candida krusei Ctropicalis Otras

N =271

Leroy O et al Crit Care Med 2009

Reduced susceptibility to fluconazole 171

Desescalated 371

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

Delaying the Empiric Treatment of Candidemia An Independent Risk Factor for Hospital Mortality

lt12 lt 24 gt24 gt48

0

5

10

15

20

25

30

35

H

ospital M

ort

alit

y

Delay in Start of Antifungal

Therapy (days)

Variable OR 95 CI P

APACHE II 124 (118-131) lt0001

Prior antibiotics 405 (214-765) 0028

Delay in antifungal 209 (153-284) 0018

therapy

Multivariate analysis of independent risk

factors for hospital mortality

Morrell et al Antimicrob Agent Chemother 2005493640

Garey KW Clin Infect Dis 2006 4325-31

The Effect of Time to Antifungal Therapy on Mortality in Candidemia associated Septic Shock

Patel GP et al Am J Therapeutics 2009

Septic shock developed in 23 (31 of 135) patients with CBSI

In-hospital mortality was 68

Appropriate antifungal therapy was

administered to 24 patients 15 (63)

of these patients died

Patients who received appropriate

antifungal therapy within 15 hours of

collecting the first positive Candida

blood culture had improved survival

(P = 003)

Caspo velocidad

Relationship between ldquoCandida scorerdquo and risk for developing IC in surgical patients

C Leon et al Crit Care Med 2009 371624 ndash1633

0

5

10

15

20

25

30

35

CSlt3 CSgt3 CS=3

Abdominal surgery

No abdominalsurgery

P lt005

IC in surgical patients according CS

NCMT NCMT

Non-culture microbiological tools [(13)-

b-D-glucan Candida albicans germ tube

antibodies or PCR

Mycoses 2010

Fluconazole To be or not to be

Jacobs et al CCM 312003

71 septic shock patients (Pneumonia=37 y Intrabadominal=34) Randomized (32 pts) 200 mg fluconazole iv vs (39 pts) placebo

Epidemiological trends in nosocomial

candidemia in intensive care

Bassetti M et al BMC Infectious Diseases 2006680

Candidemias in ICU

HUDP 1996-2007

5

95

Candidemias Bacteriemias

48

23

10

19

Candida albicans Candida glabrata Candida parapsilopsis Otras

N =397 N = 31

Mortality in C no albicans episodes

gt Calbicans (125 vs 466 p= 003)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

57

8

8

17 5

5

Candida albicans Candida glabrata Candida parapsilopsis

Candida krusei Ctropicalis Otras

N =271

Leroy O et al Crit Care Med 2009

Reduced susceptibility to fluconazole 171

Desescalated 371

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

Garey KW Clin Infect Dis 2006 4325-31

The Effect of Time to Antifungal Therapy on Mortality in Candidemia associated Septic Shock

Patel GP et al Am J Therapeutics 2009

Septic shock developed in 23 (31 of 135) patients with CBSI

In-hospital mortality was 68

Appropriate antifungal therapy was

administered to 24 patients 15 (63)

of these patients died

Patients who received appropriate

antifungal therapy within 15 hours of

collecting the first positive Candida

blood culture had improved survival

(P = 003)

Caspo velocidad

Relationship between ldquoCandida scorerdquo and risk for developing IC in surgical patients

C Leon et al Crit Care Med 2009 371624 ndash1633

0

5

10

15

20

25

30

35

CSlt3 CSgt3 CS=3

Abdominal surgery

No abdominalsurgery

P lt005

IC in surgical patients according CS

NCMT NCMT

Non-culture microbiological tools [(13)-

b-D-glucan Candida albicans germ tube

antibodies or PCR

Mycoses 2010

Fluconazole To be or not to be

Jacobs et al CCM 312003

71 septic shock patients (Pneumonia=37 y Intrabadominal=34) Randomized (32 pts) 200 mg fluconazole iv vs (39 pts) placebo

Epidemiological trends in nosocomial

candidemia in intensive care

Bassetti M et al BMC Infectious Diseases 2006680

Candidemias in ICU

HUDP 1996-2007

5

95

Candidemias Bacteriemias

48

23

10

19

Candida albicans Candida glabrata Candida parapsilopsis Otras

N =397 N = 31

Mortality in C no albicans episodes

gt Calbicans (125 vs 466 p= 003)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

57

8

8

17 5

5

Candida albicans Candida glabrata Candida parapsilopsis

Candida krusei Ctropicalis Otras

N =271

Leroy O et al Crit Care Med 2009

Reduced susceptibility to fluconazole 171

Desescalated 371

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

The Effect of Time to Antifungal Therapy on Mortality in Candidemia associated Septic Shock

Patel GP et al Am J Therapeutics 2009

Septic shock developed in 23 (31 of 135) patients with CBSI

In-hospital mortality was 68

Appropriate antifungal therapy was

administered to 24 patients 15 (63)

of these patients died

Patients who received appropriate

antifungal therapy within 15 hours of

collecting the first positive Candida

blood culture had improved survival

(P = 003)

Caspo velocidad

Relationship between ldquoCandida scorerdquo and risk for developing IC in surgical patients

C Leon et al Crit Care Med 2009 371624 ndash1633

0

5

10

15

20

25

30

35

CSlt3 CSgt3 CS=3

Abdominal surgery

No abdominalsurgery

P lt005

IC in surgical patients according CS

NCMT NCMT

Non-culture microbiological tools [(13)-

b-D-glucan Candida albicans germ tube

antibodies or PCR

Mycoses 2010

Fluconazole To be or not to be

Jacobs et al CCM 312003

71 septic shock patients (Pneumonia=37 y Intrabadominal=34) Randomized (32 pts) 200 mg fluconazole iv vs (39 pts) placebo

Epidemiological trends in nosocomial

candidemia in intensive care

Bassetti M et al BMC Infectious Diseases 2006680

Candidemias in ICU

HUDP 1996-2007

5

95

Candidemias Bacteriemias

48

23

10

19

Candida albicans Candida glabrata Candida parapsilopsis Otras

N =397 N = 31

Mortality in C no albicans episodes

gt Calbicans (125 vs 466 p= 003)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

57

8

8

17 5

5

Candida albicans Candida glabrata Candida parapsilopsis

Candida krusei Ctropicalis Otras

N =271

Leroy O et al Crit Care Med 2009

Reduced susceptibility to fluconazole 171

Desescalated 371

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

Caspo velocidad

Relationship between ldquoCandida scorerdquo and risk for developing IC in surgical patients

C Leon et al Crit Care Med 2009 371624 ndash1633

0

5

10

15

20

25

30

35

CSlt3 CSgt3 CS=3

Abdominal surgery

No abdominalsurgery

P lt005

IC in surgical patients according CS

NCMT NCMT

Non-culture microbiological tools [(13)-

b-D-glucan Candida albicans germ tube

antibodies or PCR

Mycoses 2010

Fluconazole To be or not to be

Jacobs et al CCM 312003

71 septic shock patients (Pneumonia=37 y Intrabadominal=34) Randomized (32 pts) 200 mg fluconazole iv vs (39 pts) placebo

Epidemiological trends in nosocomial

candidemia in intensive care

Bassetti M et al BMC Infectious Diseases 2006680

Candidemias in ICU

HUDP 1996-2007

5

95

Candidemias Bacteriemias

48

23

10

19

Candida albicans Candida glabrata Candida parapsilopsis Otras

N =397 N = 31

Mortality in C no albicans episodes

gt Calbicans (125 vs 466 p= 003)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

57

8

8

17 5

5

Candida albicans Candida glabrata Candida parapsilopsis

Candida krusei Ctropicalis Otras

N =271

Leroy O et al Crit Care Med 2009

Reduced susceptibility to fluconazole 171

Desescalated 371

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

Relationship between ldquoCandida scorerdquo and risk for developing IC in surgical patients

C Leon et al Crit Care Med 2009 371624 ndash1633

0

5

10

15

20

25

30

35

CSlt3 CSgt3 CS=3

Abdominal surgery

No abdominalsurgery

P lt005

IC in surgical patients according CS

NCMT NCMT

Non-culture microbiological tools [(13)-

b-D-glucan Candida albicans germ tube

antibodies or PCR

Mycoses 2010

Fluconazole To be or not to be

Jacobs et al CCM 312003

71 septic shock patients (Pneumonia=37 y Intrabadominal=34) Randomized (32 pts) 200 mg fluconazole iv vs (39 pts) placebo

Epidemiological trends in nosocomial

candidemia in intensive care

Bassetti M et al BMC Infectious Diseases 2006680

Candidemias in ICU

HUDP 1996-2007

5

95

Candidemias Bacteriemias

48

23

10

19

Candida albicans Candida glabrata Candida parapsilopsis Otras

N =397 N = 31

Mortality in C no albicans episodes

gt Calbicans (125 vs 466 p= 003)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

57

8

8

17 5

5

Candida albicans Candida glabrata Candida parapsilopsis

Candida krusei Ctropicalis Otras

N =271

Leroy O et al Crit Care Med 2009

Reduced susceptibility to fluconazole 171

Desescalated 371

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

NCMT NCMT

Non-culture microbiological tools [(13)-

b-D-glucan Candida albicans germ tube

antibodies or PCR

Mycoses 2010

Fluconazole To be or not to be

Jacobs et al CCM 312003

71 septic shock patients (Pneumonia=37 y Intrabadominal=34) Randomized (32 pts) 200 mg fluconazole iv vs (39 pts) placebo

Epidemiological trends in nosocomial

candidemia in intensive care

Bassetti M et al BMC Infectious Diseases 2006680

Candidemias in ICU

HUDP 1996-2007

5

95

Candidemias Bacteriemias

48

23

10

19

Candida albicans Candida glabrata Candida parapsilopsis Otras

N =397 N = 31

Mortality in C no albicans episodes

gt Calbicans (125 vs 466 p= 003)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

57

8

8

17 5

5

Candida albicans Candida glabrata Candida parapsilopsis

Candida krusei Ctropicalis Otras

N =271

Leroy O et al Crit Care Med 2009

Reduced susceptibility to fluconazole 171

Desescalated 371

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

Fluconazole To be or not to be

Jacobs et al CCM 312003

71 septic shock patients (Pneumonia=37 y Intrabadominal=34) Randomized (32 pts) 200 mg fluconazole iv vs (39 pts) placebo

Epidemiological trends in nosocomial

candidemia in intensive care

Bassetti M et al BMC Infectious Diseases 2006680

Candidemias in ICU

HUDP 1996-2007

5

95

Candidemias Bacteriemias

48

23

10

19

Candida albicans Candida glabrata Candida parapsilopsis Otras

N =397 N = 31

Mortality in C no albicans episodes

gt Calbicans (125 vs 466 p= 003)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

57

8

8

17 5

5

Candida albicans Candida glabrata Candida parapsilopsis

Candida krusei Ctropicalis Otras

N =271

Leroy O et al Crit Care Med 2009

Reduced susceptibility to fluconazole 171

Desescalated 371

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

Jacobs et al CCM 312003

71 septic shock patients (Pneumonia=37 y Intrabadominal=34) Randomized (32 pts) 200 mg fluconazole iv vs (39 pts) placebo

Epidemiological trends in nosocomial

candidemia in intensive care

Bassetti M et al BMC Infectious Diseases 2006680

Candidemias in ICU

HUDP 1996-2007

5

95

Candidemias Bacteriemias

48

23

10

19

Candida albicans Candida glabrata Candida parapsilopsis Otras

N =397 N = 31

Mortality in C no albicans episodes

gt Calbicans (125 vs 466 p= 003)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

57

8

8

17 5

5

Candida albicans Candida glabrata Candida parapsilopsis

Candida krusei Ctropicalis Otras

N =271

Leroy O et al Crit Care Med 2009

Reduced susceptibility to fluconazole 171

Desescalated 371

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

Epidemiological trends in nosocomial

candidemia in intensive care

Bassetti M et al BMC Infectious Diseases 2006680

Candidemias in ICU

HUDP 1996-2007

5

95

Candidemias Bacteriemias

48

23

10

19

Candida albicans Candida glabrata Candida parapsilopsis Otras

N =397 N = 31

Mortality in C no albicans episodes

gt Calbicans (125 vs 466 p= 003)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

57

8

8

17 5

5

Candida albicans Candida glabrata Candida parapsilopsis

Candida krusei Ctropicalis Otras

N =271

Leroy O et al Crit Care Med 2009

Reduced susceptibility to fluconazole 171

Desescalated 371

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

Candidemias in ICU

HUDP 1996-2007

5

95

Candidemias Bacteriemias

48

23

10

19

Candida albicans Candida glabrata Candida parapsilopsis Otras

N =397 N = 31

Mortality in C no albicans episodes

gt Calbicans (125 vs 466 p= 003)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

57

8

8

17 5

5

Candida albicans Candida glabrata Candida parapsilopsis

Candida krusei Ctropicalis Otras

N =271

Leroy O et al Crit Care Med 2009

Reduced susceptibility to fluconazole 171

Desescalated 371

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

57

8

8

17 5

5

Candida albicans Candida glabrata Candida parapsilopsis

Candida krusei Ctropicalis Otras

N =271

Leroy O et al Crit Care Med 2009

Reduced susceptibility to fluconazole 171

Desescalated 371

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

Epidemiology management and risk factors for death of invasive Candida infections in critical care A multicenter prospective observational study in France (2005ndash2006)

Leroy O et al Crit Care Med 2009

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

CANDIPOP Study ( 752 episodes)

12 months of candidemias in Spain (2010-2011)

Overall rate of fluconazole resistance (MICgt4 μgml) was 146

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

Risk factors for fluconazole-resistant

Candida glabrata bloodstream infections

76 C glabrata R fluconazole

68 C glabrata S fluconazole

512 controls

Lee I et al Arch Intern Med 2009 Feb 23169(4)379-83

Fluco R OR (95IC ) Previos use of fluconazol 23 (13-42)

Previos use of linezolid 46 ( 22-93)

Fluco S OR (95IC) Previous use of cefepime 22 (12-39)

Previous use of metronidazol

2 ( 11-35)

Risk Factors for Fluconazole-Resistant Candidemia

bull Prospective study including adult patients with candidemia (226 episodios)

ndash Non-albicans 53

ndash Potentially fluconazole resistant 18

bull Isolates microbiologically confirmed fluconazole resistance 13

J Garnacho et al Antimicrob Agents Chemother 2010

Previous fluconazole exposure is an independent risk factor for candidemia caused by microbiologically

confirmed fluconazole resistant species but not for bloodstream infection caused by non-albicans Candida

spp or by potentially fluconazole-resistant Candida spp (C glabrata and C krusei) Our findings may be of

value for selecting empirical antifungal therapy

INDEPENDENT PREDICTORS OR

Neutropenia 494

Chronic renal disease 482

Previous Fluconazole exposure 509

C glabrata (14) C krusei (14)

C tropicalis (2)

Baddley

p=0009

Global mortality 28 (n=84)

0

5

10

15

20

25

R Fluconazole

Alive

Dead

p = 002

Association of Fluconazole AUCMIC and DoseMIC Ratios

with Mortality in Non-neutropenic Patients with

Candidemia

0

5

10

15

Survivors Non

Survivors

Dose MI C

p = 003

Pai M et al Antimicrob Agents Chemother 2007 51 35

A new schemehellip Invasive Candidiasis in ICU

The case for antifungal stewardship

bull httpwwwdisfrutalogratiscomcochesoporto2jpg

bull Introduction and definition

How to do it

bull Is de-escalation a real practise

bull Is an early broad spectrum

antifungal treatment needed

bull Do we need it Fluconazole

bull Which situations

bull NEVER

bull SOMETIMES

bull ALWAYS

bull When can we step down

ndash If case of proven IC

ndash If IC are not proven

bull Take home messages

NEVER USE DE-ESCALATION STRATEGY NEVER STEP DOWN TO FLUCONAZOLEhellipif

CRRT

AVOID INTERACTIONS specially with

inmunossupresive agents

Hepatic failure

C glabrata amp C krusei ETIOLOGY

Personal opinion

TIME TO STEP DOWN

5 DAYS

10 DAYS

I DO NOT KNOW BUT PROBABLYhellip

Personal opinion

IDSA VS ESCMID

USE DE-ESCALATION STRATEGY WITHDRAW ANY ANTIFUNGAL DRUG hellipif

Personal opinion

Documentation of another etiology Or Documentation of other sources of infection Or No positive result of Platelia after 10 days and improvement of scores PCT gt 55 ngml on day 5

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

Personal opinion

If invasive candidiasis is confirmed by positive blood culture or sterile site after knowing susceptibility to fluconazole and the patient has recovered from MOF

Blood cultures= 50 sensitivity

iquest What can we do

PROFILAXIS Tratamiento

anticipado Tratamiento

empiacuterico

Tratamiento

dirigido

Zaragoza R et al Clin Ther Risk Man 2008 Dec

Charles PE et al Intensive Care Med 2006 32 1577-1583

Retrospective study

50 bloodstream infections 15 candidemias (11 patients) y 35 bacteremias (33

patients)

PCT gt 55 ngml NPV for candidemia

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-

Zeichner prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-Zeichner

prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

FUNGAL BIOMARKERS

Kinetic Patterns of Candida albicans Germ Tube

Antibody (CAGTA) in Critically Ill Patients Influence

on Mortality

0

66

143

307

0

10

20

30

40

50

60

70

Treated

patients

All patients

Mortality

IncreasingCAGTA

No increasingCAGTA

2253 CAGTA +

318 Increasing titers

364 Decreasing titers

228 No change

p = 008 p = 004

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

Baddley

p=0009

Global mortality 28 (n=84)

0

5

10

15

20

25

R Fluconazole

Alive

Dead

p = 002

Association of Fluconazole AUCMIC and DoseMIC Ratios

with Mortality in Non-neutropenic Patients with

Candidemia

0

5

10

15

Survivors Non

Survivors

Dose MI C

p = 003

Pai M et al Antimicrob Agents Chemother 2007 51 35

A new schemehellip Invasive Candidiasis in ICU

The case for antifungal stewardship

bull httpwwwdisfrutalogratiscomcochesoporto2jpg

bull Introduction and definition

How to do it

bull Is de-escalation a real practise

bull Is an early broad spectrum

antifungal treatment needed

bull Do we need it Fluconazole

bull Which situations

bull NEVER

bull SOMETIMES

bull ALWAYS

bull When can we step down

ndash If case of proven IC

ndash If IC are not proven

bull Take home messages

NEVER USE DE-ESCALATION STRATEGY NEVER STEP DOWN TO FLUCONAZOLEhellipif

CRRT

AVOID INTERACTIONS specially with

inmunossupresive agents

Hepatic failure

C glabrata amp C krusei ETIOLOGY

Personal opinion

TIME TO STEP DOWN

5 DAYS

10 DAYS

I DO NOT KNOW BUT PROBABLYhellip

Personal opinion

IDSA VS ESCMID

USE DE-ESCALATION STRATEGY WITHDRAW ANY ANTIFUNGAL DRUG hellipif

Personal opinion

Documentation of another etiology Or Documentation of other sources of infection Or No positive result of Platelia after 10 days and improvement of scores PCT gt 55 ngml on day 5

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

Personal opinion

If invasive candidiasis is confirmed by positive blood culture or sterile site after knowing susceptibility to fluconazole and the patient has recovered from MOF

Blood cultures= 50 sensitivity

iquest What can we do

PROFILAXIS Tratamiento

anticipado Tratamiento

empiacuterico

Tratamiento

dirigido

Zaragoza R et al Clin Ther Risk Man 2008 Dec

Charles PE et al Intensive Care Med 2006 32 1577-1583

Retrospective study

50 bloodstream infections 15 candidemias (11 patients) y 35 bacteremias (33

patients)

PCT gt 55 ngml NPV for candidemia

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-

Zeichner prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-Zeichner

prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

FUNGAL BIOMARKERS

Kinetic Patterns of Candida albicans Germ Tube

Antibody (CAGTA) in Critically Ill Patients Influence

on Mortality

0

66

143

307

0

10

20

30

40

50

60

70

Treated

patients

All patients

Mortality

IncreasingCAGTA

No increasingCAGTA

2253 CAGTA +

318 Increasing titers

364 Decreasing titers

228 No change

p = 008 p = 004

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

Global mortality 28 (n=84)

0

5

10

15

20

25

R Fluconazole

Alive

Dead

p = 002

Association of Fluconazole AUCMIC and DoseMIC Ratios

with Mortality in Non-neutropenic Patients with

Candidemia

0

5

10

15

Survivors Non

Survivors

Dose MI C

p = 003

Pai M et al Antimicrob Agents Chemother 2007 51 35

A new schemehellip Invasive Candidiasis in ICU

The case for antifungal stewardship

bull httpwwwdisfrutalogratiscomcochesoporto2jpg

bull Introduction and definition

How to do it

bull Is de-escalation a real practise

bull Is an early broad spectrum

antifungal treatment needed

bull Do we need it Fluconazole

bull Which situations

bull NEVER

bull SOMETIMES

bull ALWAYS

bull When can we step down

ndash If case of proven IC

ndash If IC are not proven

bull Take home messages

NEVER USE DE-ESCALATION STRATEGY NEVER STEP DOWN TO FLUCONAZOLEhellipif

CRRT

AVOID INTERACTIONS specially with

inmunossupresive agents

Hepatic failure

C glabrata amp C krusei ETIOLOGY

Personal opinion

TIME TO STEP DOWN

5 DAYS

10 DAYS

I DO NOT KNOW BUT PROBABLYhellip

Personal opinion

IDSA VS ESCMID

USE DE-ESCALATION STRATEGY WITHDRAW ANY ANTIFUNGAL DRUG hellipif

Personal opinion

Documentation of another etiology Or Documentation of other sources of infection Or No positive result of Platelia after 10 days and improvement of scores PCT gt 55 ngml on day 5

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

Personal opinion

If invasive candidiasis is confirmed by positive blood culture or sterile site after knowing susceptibility to fluconazole and the patient has recovered from MOF

Blood cultures= 50 sensitivity

iquest What can we do

PROFILAXIS Tratamiento

anticipado Tratamiento

empiacuterico

Tratamiento

dirigido

Zaragoza R et al Clin Ther Risk Man 2008 Dec

Charles PE et al Intensive Care Med 2006 32 1577-1583

Retrospective study

50 bloodstream infections 15 candidemias (11 patients) y 35 bacteremias (33

patients)

PCT gt 55 ngml NPV for candidemia

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-

Zeichner prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-Zeichner

prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

FUNGAL BIOMARKERS

Kinetic Patterns of Candida albicans Germ Tube

Antibody (CAGTA) in Critically Ill Patients Influence

on Mortality

0

66

143

307

0

10

20

30

40

50

60

70

Treated

patients

All patients

Mortality

IncreasingCAGTA

No increasingCAGTA

2253 CAGTA +

318 Increasing titers

364 Decreasing titers

228 No change

p = 008 p = 004

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

Association of Fluconazole AUCMIC and DoseMIC Ratios

with Mortality in Non-neutropenic Patients with

Candidemia

0

5

10

15

Survivors Non

Survivors

Dose MI C

p = 003

Pai M et al Antimicrob Agents Chemother 2007 51 35

A new schemehellip Invasive Candidiasis in ICU

The case for antifungal stewardship

bull httpwwwdisfrutalogratiscomcochesoporto2jpg

bull Introduction and definition

How to do it

bull Is de-escalation a real practise

bull Is an early broad spectrum

antifungal treatment needed

bull Do we need it Fluconazole

bull Which situations

bull NEVER

bull SOMETIMES

bull ALWAYS

bull When can we step down

ndash If case of proven IC

ndash If IC are not proven

bull Take home messages

NEVER USE DE-ESCALATION STRATEGY NEVER STEP DOWN TO FLUCONAZOLEhellipif

CRRT

AVOID INTERACTIONS specially with

inmunossupresive agents

Hepatic failure

C glabrata amp C krusei ETIOLOGY

Personal opinion

TIME TO STEP DOWN

5 DAYS

10 DAYS

I DO NOT KNOW BUT PROBABLYhellip

Personal opinion

IDSA VS ESCMID

USE DE-ESCALATION STRATEGY WITHDRAW ANY ANTIFUNGAL DRUG hellipif

Personal opinion

Documentation of another etiology Or Documentation of other sources of infection Or No positive result of Platelia after 10 days and improvement of scores PCT gt 55 ngml on day 5

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

Personal opinion

If invasive candidiasis is confirmed by positive blood culture or sterile site after knowing susceptibility to fluconazole and the patient has recovered from MOF

Blood cultures= 50 sensitivity

iquest What can we do

PROFILAXIS Tratamiento

anticipado Tratamiento

empiacuterico

Tratamiento

dirigido

Zaragoza R et al Clin Ther Risk Man 2008 Dec

Charles PE et al Intensive Care Med 2006 32 1577-1583

Retrospective study

50 bloodstream infections 15 candidemias (11 patients) y 35 bacteremias (33

patients)

PCT gt 55 ngml NPV for candidemia

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-

Zeichner prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-Zeichner

prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

FUNGAL BIOMARKERS

Kinetic Patterns of Candida albicans Germ Tube

Antibody (CAGTA) in Critically Ill Patients Influence

on Mortality

0

66

143

307

0

10

20

30

40

50

60

70

Treated

patients

All patients

Mortality

IncreasingCAGTA

No increasingCAGTA

2253 CAGTA +

318 Increasing titers

364 Decreasing titers

228 No change

p = 008 p = 004

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

A new schemehellip Invasive Candidiasis in ICU

The case for antifungal stewardship

bull httpwwwdisfrutalogratiscomcochesoporto2jpg

bull Introduction and definition

How to do it

bull Is de-escalation a real practise

bull Is an early broad spectrum

antifungal treatment needed

bull Do we need it Fluconazole

bull Which situations

bull NEVER

bull SOMETIMES

bull ALWAYS

bull When can we step down

ndash If case of proven IC

ndash If IC are not proven

bull Take home messages

NEVER USE DE-ESCALATION STRATEGY NEVER STEP DOWN TO FLUCONAZOLEhellipif

CRRT

AVOID INTERACTIONS specially with

inmunossupresive agents

Hepatic failure

C glabrata amp C krusei ETIOLOGY

Personal opinion

TIME TO STEP DOWN

5 DAYS

10 DAYS

I DO NOT KNOW BUT PROBABLYhellip

Personal opinion

IDSA VS ESCMID

USE DE-ESCALATION STRATEGY WITHDRAW ANY ANTIFUNGAL DRUG hellipif

Personal opinion

Documentation of another etiology Or Documentation of other sources of infection Or No positive result of Platelia after 10 days and improvement of scores PCT gt 55 ngml on day 5

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

Personal opinion

If invasive candidiasis is confirmed by positive blood culture or sterile site after knowing susceptibility to fluconazole and the patient has recovered from MOF

Blood cultures= 50 sensitivity

iquest What can we do

PROFILAXIS Tratamiento

anticipado Tratamiento

empiacuterico

Tratamiento

dirigido

Zaragoza R et al Clin Ther Risk Man 2008 Dec

Charles PE et al Intensive Care Med 2006 32 1577-1583

Retrospective study

50 bloodstream infections 15 candidemias (11 patients) y 35 bacteremias (33

patients)

PCT gt 55 ngml NPV for candidemia

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-

Zeichner prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-Zeichner

prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

FUNGAL BIOMARKERS

Kinetic Patterns of Candida albicans Germ Tube

Antibody (CAGTA) in Critically Ill Patients Influence

on Mortality

0

66

143

307

0

10

20

30

40

50

60

70

Treated

patients

All patients

Mortality

IncreasingCAGTA

No increasingCAGTA

2253 CAGTA +

318 Increasing titers

364 Decreasing titers

228 No change

p = 008 p = 004

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

NEVER USE DE-ESCALATION STRATEGY NEVER STEP DOWN TO FLUCONAZOLEhellipif

CRRT

AVOID INTERACTIONS specially with

inmunossupresive agents

Hepatic failure

C glabrata amp C krusei ETIOLOGY

Personal opinion

TIME TO STEP DOWN

5 DAYS

10 DAYS

I DO NOT KNOW BUT PROBABLYhellip

Personal opinion

IDSA VS ESCMID

USE DE-ESCALATION STRATEGY WITHDRAW ANY ANTIFUNGAL DRUG hellipif

Personal opinion

Documentation of another etiology Or Documentation of other sources of infection Or No positive result of Platelia after 10 days and improvement of scores PCT gt 55 ngml on day 5

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

Personal opinion

If invasive candidiasis is confirmed by positive blood culture or sterile site after knowing susceptibility to fluconazole and the patient has recovered from MOF

Blood cultures= 50 sensitivity

iquest What can we do

PROFILAXIS Tratamiento

anticipado Tratamiento

empiacuterico

Tratamiento

dirigido

Zaragoza R et al Clin Ther Risk Man 2008 Dec

Charles PE et al Intensive Care Med 2006 32 1577-1583

Retrospective study

50 bloodstream infections 15 candidemias (11 patients) y 35 bacteremias (33

patients)

PCT gt 55 ngml NPV for candidemia

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-

Zeichner prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-Zeichner

prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

FUNGAL BIOMARKERS

Kinetic Patterns of Candida albicans Germ Tube

Antibody (CAGTA) in Critically Ill Patients Influence

on Mortality

0

66

143

307

0

10

20

30

40

50

60

70

Treated

patients

All patients

Mortality

IncreasingCAGTA

No increasingCAGTA

2253 CAGTA +

318 Increasing titers

364 Decreasing titers

228 No change

p = 008 p = 004

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

TIME TO STEP DOWN

5 DAYS

10 DAYS

I DO NOT KNOW BUT PROBABLYhellip

Personal opinion

IDSA VS ESCMID

USE DE-ESCALATION STRATEGY WITHDRAW ANY ANTIFUNGAL DRUG hellipif

Personal opinion

Documentation of another etiology Or Documentation of other sources of infection Or No positive result of Platelia after 10 days and improvement of scores PCT gt 55 ngml on day 5

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

Personal opinion

If invasive candidiasis is confirmed by positive blood culture or sterile site after knowing susceptibility to fluconazole and the patient has recovered from MOF

Blood cultures= 50 sensitivity

iquest What can we do

PROFILAXIS Tratamiento

anticipado Tratamiento

empiacuterico

Tratamiento

dirigido

Zaragoza R et al Clin Ther Risk Man 2008 Dec

Charles PE et al Intensive Care Med 2006 32 1577-1583

Retrospective study

50 bloodstream infections 15 candidemias (11 patients) y 35 bacteremias (33

patients)

PCT gt 55 ngml NPV for candidemia

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-

Zeichner prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-Zeichner

prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

FUNGAL BIOMARKERS

Kinetic Patterns of Candida albicans Germ Tube

Antibody (CAGTA) in Critically Ill Patients Influence

on Mortality

0

66

143

307

0

10

20

30

40

50

60

70

Treated

patients

All patients

Mortality

IncreasingCAGTA

No increasingCAGTA

2253 CAGTA +

318 Increasing titers

364 Decreasing titers

228 No change

p = 008 p = 004

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

USE DE-ESCALATION STRATEGY WITHDRAW ANY ANTIFUNGAL DRUG hellipif

Personal opinion

Documentation of another etiology Or Documentation of other sources of infection Or No positive result of Platelia after 10 days and improvement of scores PCT gt 55 ngml on day 5

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

Personal opinion

If invasive candidiasis is confirmed by positive blood culture or sterile site after knowing susceptibility to fluconazole and the patient has recovered from MOF

Blood cultures= 50 sensitivity

iquest What can we do

PROFILAXIS Tratamiento

anticipado Tratamiento

empiacuterico

Tratamiento

dirigido

Zaragoza R et al Clin Ther Risk Man 2008 Dec

Charles PE et al Intensive Care Med 2006 32 1577-1583

Retrospective study

50 bloodstream infections 15 candidemias (11 patients) y 35 bacteremias (33

patients)

PCT gt 55 ngml NPV for candidemia

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-

Zeichner prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-Zeichner

prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

FUNGAL BIOMARKERS

Kinetic Patterns of Candida albicans Germ Tube

Antibody (CAGTA) in Critically Ill Patients Influence

on Mortality

0

66

143

307

0

10

20

30

40

50

60

70

Treated

patients

All patients

Mortality

IncreasingCAGTA

No increasingCAGTA

2253 CAGTA +

318 Increasing titers

364 Decreasing titers

228 No change

p = 008 p = 004

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

Personal opinion

If invasive candidiasis is confirmed by positive blood culture or sterile site after knowing susceptibility to fluconazole and the patient has recovered from MOF

Blood cultures= 50 sensitivity

iquest What can we do

PROFILAXIS Tratamiento

anticipado Tratamiento

empiacuterico

Tratamiento

dirigido

Zaragoza R et al Clin Ther Risk Man 2008 Dec

Charles PE et al Intensive Care Med 2006 32 1577-1583

Retrospective study

50 bloodstream infections 15 candidemias (11 patients) y 35 bacteremias (33

patients)

PCT gt 55 ngml NPV for candidemia

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-

Zeichner prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-Zeichner

prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

FUNGAL BIOMARKERS

Kinetic Patterns of Candida albicans Germ Tube

Antibody (CAGTA) in Critically Ill Patients Influence

on Mortality

0

66

143

307

0

10

20

30

40

50

60

70

Treated

patients

All patients

Mortality

IncreasingCAGTA

No increasingCAGTA

2253 CAGTA +

318 Increasing titers

364 Decreasing titers

228 No change

p = 008 p = 004

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

Blood cultures= 50 sensitivity

iquest What can we do

PROFILAXIS Tratamiento

anticipado Tratamiento

empiacuterico

Tratamiento

dirigido

Zaragoza R et al Clin Ther Risk Man 2008 Dec

Charles PE et al Intensive Care Med 2006 32 1577-1583

Retrospective study

50 bloodstream infections 15 candidemias (11 patients) y 35 bacteremias (33

patients)

PCT gt 55 ngml NPV for candidemia

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-

Zeichner prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-Zeichner

prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

FUNGAL BIOMARKERS

Kinetic Patterns of Candida albicans Germ Tube

Antibody (CAGTA) in Critically Ill Patients Influence

on Mortality

0

66

143

307

0

10

20

30

40

50

60

70

Treated

patients

All patients

Mortality

IncreasingCAGTA

No increasingCAGTA

2253 CAGTA +

318 Increasing titers

364 Decreasing titers

228 No change

p = 008 p = 004

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

iquest What can we do

PROFILAXIS Tratamiento

anticipado Tratamiento

empiacuterico

Tratamiento

dirigido

Zaragoza R et al Clin Ther Risk Man 2008 Dec

Charles PE et al Intensive Care Med 2006 32 1577-1583

Retrospective study

50 bloodstream infections 15 candidemias (11 patients) y 35 bacteremias (33

patients)

PCT gt 55 ngml NPV for candidemia

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-

Zeichner prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-Zeichner

prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

FUNGAL BIOMARKERS

Kinetic Patterns of Candida albicans Germ Tube

Antibody (CAGTA) in Critically Ill Patients Influence

on Mortality

0

66

143

307

0

10

20

30

40

50

60

70

Treated

patients

All patients

Mortality

IncreasingCAGTA

No increasingCAGTA

2253 CAGTA +

318 Increasing titers

364 Decreasing titers

228 No change

p = 008 p = 004

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

Charles PE et al Intensive Care Med 2006 32 1577-1583

Retrospective study

50 bloodstream infections 15 candidemias (11 patients) y 35 bacteremias (33

patients)

PCT gt 55 ngml NPV for candidemia

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-

Zeichner prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-Zeichner

prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

FUNGAL BIOMARKERS

Kinetic Patterns of Candida albicans Germ Tube

Antibody (CAGTA) in Critically Ill Patients Influence

on Mortality

0

66

143

307

0

10

20

30

40

50

60

70

Treated

patients

All patients

Mortality

IncreasingCAGTA

No increasingCAGTA

2253 CAGTA +

318 Increasing titers

364 Decreasing titers

228 No change

p = 008 p = 004

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-

Zeichner prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-Zeichner

prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

FUNGAL BIOMARKERS

Kinetic Patterns of Candida albicans Germ Tube

Antibody (CAGTA) in Critically Ill Patients Influence

on Mortality

0

66

143

307

0

10

20

30

40

50

60

70

Treated

patients

All patients

Mortality

IncreasingCAGTA

No increasingCAGTA

2253 CAGTA +

318 Increasing titers

364 Decreasing titers

228 No change

p = 008 p = 004

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

Multidisciplinary approach to the treatment of invasive fungal infections in adult patients Prophylaxis empirical preemptive or targeted therapy which is the best in the different hosts Rafael Zaragoza Javier Pemaacuten Miguel Salavert Aacutengel Viudes Amparo Soleacute Isidro Jarque Emilio Monte Eva Romaacute Emilia Cantoacuten

Clin Ther Risk Man 2008 Dec

Strategy Antifungal agent References

Prophylaxis No generally recommended Patients with upper

gastrointestinal perforation heavy Candida

colonization or with severe acute pancreatitis

might be benefit

Fluconazole (Pelz et al 2001) (Garbino et al

2002) (De Waele et al

2003Piarroux et al 2004)

Empirical Use of ldquoCandida scorerdquo or the Ostrosky-Zeichner

prediction rule

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Leon et al 2006Ostrosky-

Zeichner et al 2007)

Pre-emptive Based on detection of galactomannan (13)--d-

glucan or C albicans germ tube antibodies or

PCR

De-escalation therapy ()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient

(Meersseman et al

2008Ostrosky-Zeichner et al

2005Zaragoza et al 2006)

Targeted Based on sterile site culture results De-escalation therapy()

the choice of antifungal

drug must be based on the

individual characteristics

of the patient ()

(Kullberg et al 2005Kuse et al

2007Mora-Duarte et al

2002Pappas et al 2007Phillips

et al 1997Rex et al

1994Zaragoza amp Peman 2006)

FUNGAL BIOMARKERS

Kinetic Patterns of Candida albicans Germ Tube

Antibody (CAGTA) in Critically Ill Patients Influence

on Mortality

0

66

143

307

0

10

20

30

40

50

60

70

Treated

patients

All patients

Mortality

IncreasingCAGTA

No increasingCAGTA

2253 CAGTA +

318 Increasing titers

364 Decreasing titers

228 No change

p = 008 p = 004

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

FUNGAL BIOMARKERS

Kinetic Patterns of Candida albicans Germ Tube

Antibody (CAGTA) in Critically Ill Patients Influence

on Mortality

0

66

143

307

0

10

20

30

40

50

60

70

Treated

patients

All patients

Mortality

IncreasingCAGTA

No increasingCAGTA

2253 CAGTA +

318 Increasing titers

364 Decreasing titers

228 No change

p = 008 p = 004

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

Kinetic Patterns of Candida albicans Germ Tube

Antibody (CAGTA) in Critically Ill Patients Influence

on Mortality

0

66

143

307

0

10

20

30

40

50

60

70

Treated

patients

All patients

Mortality

IncreasingCAGTA

No increasingCAGTA

2253 CAGTA +

318 Increasing titers

364 Decreasing titers

228 No change

p = 008 p = 004

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

CAGTA

Monitorizing the treatment

Iruretagoyena JR Reguacutelez P Quindoacutes G Pontoacuten J Rev Iberoam Micol 2006 Mar23(1)50-3

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

USE DE-ESCALATION STRATEGY STEPING DOWN TO FLUCONAZOLEhellipif

If IC is not confirmed (one of them)

Improvement of scores (SOFA and CS)

Negative result of Platelia (if any previous

sample was positive) or another biomarker

No positive result of Platelia on days 5 or 10 or

another biomarker

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

TAKE HOME MESSAGES

1 TREAT AS SOON AS POSSIBLE WITH A BROAD

SPECTRUM ANTIFUNGAL DRUG

2 FOLLOW A DE-ESCALATION PROTOCOL

COMBINE CLINICAL AND MICROBIOLOGICAL

DATA

3 DO NOT WORRY ABOUT WITHDRAW IF YOU ARE

SURE

4 USE FLUCONAZOLE WHEN THE SITUATION

OFTHE PATIENT ALLOW YOU TO DO IT

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

Nike

I HOPE YOU AGREE WITH ME

Fith recommendation

bull Do not wait for last talk

Fith recommendation

bull Do not wait for last talk