New Guidelines for Hospital-New Guidelines for Hospital-Acquired Pneumonia (HAP) Acquired Pneumonia (HAP)

& Ventilator-Associated & Ventilator-Associated Pneumonia (VAP)Pneumonia (VAP)

Dr. Bawoh MDr. Bawoh M

Clinical Trial Center, YSMA- RussiaClinical Trial Center, YSMA- Russia

Guideline Formulation Guideline Formulation ParticipantsParticipants

Association of Medical Microbiology and Association of Medical Microbiology and Infectious Disease Canada (AMMI Infectious Disease Canada (AMMI Canada)Canada)

Canadian Thoracic Society (CTS)Canadian Thoracic Society (CTS)

Intensive visits Intensive visits

PharmacistsPharmacists

Epidemiology of Epidemiology of HAP-VAPHAP-VAP

Hospital-Acquired Hospital-Acquired Pneumonia (HAP): Pneumonia (HAP):

DefinitionsDefinitions HAP:HAP:

Arises 48 hours or more after hospital Arises 48 hours or more after hospital admissionadmission

Is not incubating at the time of admissionIs not incubating at the time of admission Ventilator-associated pneumonia (VAP):Ventilator-associated pneumonia (VAP):

Arises 48-72 hours or more after Arises 48-72 hours or more after endotracheal intubation endotracheal intubation

Healthcare-associated pneumonia (HCAP):Healthcare-associated pneumonia (HCAP): Arises within 90 days of having been Arises within 90 days of having been

admitted to an acute care facility & pt. has admitted to an acute care facility & pt. has resided in a nursing home or LTCF. resided in a nursing home or LTCF.

(American Thoracic Society/IDSA. Am J Respir Crit Care Med 2005;171:388-416)(American Thoracic Society/IDSA. Am J Respir Crit Care Med 2005;171:388-416)

HAP: ImpactHAP: Impact

Accounts forAccounts for ~15% of all nosocomial ~15% of all nosocomial infections (2infections (2ndnd most common cause of NI’s most common cause of NI’s after UTI’s)after UTI’s)

Number of cases per year in US:Number of cases per year in US: ~275,000~275,000

Extra days in the hospital:Extra days in the hospital: 4-9 days 4-9 days Average extra days in ICU:Average extra days in ICU: 4.3 days 4.3 days Direct costDirect cost (estimated) of excess hospital (estimated) of excess hospital

staystay = $1.5 billion per year = $1.5 billion per year

IncidenceIncidence

Hospital Location & Hospital Location & Relative Frequency of Relative Frequency of

HAP & VAPHAP & VAP

HAPHAP14%14%

ICU ICU HAPHAP37.5%37.5%

Non-ICU Non-ICU HAPHAP62.5%62.5%

VAPVAP86%86%

Non-ICU HAPNon-ICU HAP

ICU HAPICU HAP

VAPVAP

ICU HAPICU HAP

HAPHAP ICUICU

(Kumpf G et al. J Clin Epidemiol 1998;54:495-502)(Kumpf G et al. J Clin Epidemiol 1998;54:495-502)(Lizioli A et al. J Hosp Infect 2003;54:141-148)(Lizioli A et al. J Hosp Infect 2003;54:141-148)(Richards MJ et al. Crit Care Med 1999;27:887-(Richards MJ et al. Crit Care Med 1999;27:887-892)892)

INCIDENCE OF NOSOCOMIAL INFECTIONS INCIDENCE OF NOSOCOMIAL INFECTIONS IN COMBINED MEDICAL-SURGICAL ICU’sIN COMBINED MEDICAL-SURGICAL ICU’s

Medical PatientsMedical Patients Surgical PatientsSurgical Patients

PneumoniaPneumonia 30% 30% PneumoniaPneumonia 33% 33%

UTIUTI 30% 30% UTIUTI 18% 18%

BloodstreamBloodstream SSTISSTI 14% 14%

infectioninfection 16% 16% BloodstreamBloodstream

Lower resp. Lower resp. infection infection 13% 13%

tract tract 6% 6% Lower resp.Lower resp.

(not pneumonia)(not pneumonia) tracttract 6% 6%

(not pneumonia)(not pneumonia)

(Richards et al. Infect Control Hosp Epidemiol 2000;21:510-515)(Richards et al. Infect Control Hosp Epidemiol 2000;21:510-515)

Risk Factors for Risk Factors for HAP & VAPHAP & VAP

Risk Risk FactorsFactors for for HAP/VAPHAP/VAP

Co-morbid Co-morbid IllnessesIllnesses ICU TherapiesICU Therapies InjuriesInjuries VentilationVentilation

CancerCancer Chronic Chronic

obstructive obstructive pulmonary pulmonary disease disease (COPD)(COPD)

Chronic Chronic cardiac cardiac diseasedisease

Kidney failureKidney failure

CPRCPR Corticosteroid Corticosteroid

useuse General surgeryGeneral surgery NeurosurgeryNeurosurgery AntacidsAntacids Paralytic agentsParalytic agents Prior antibiotic Prior antibiotic

therapytherapy TracheostomyTracheostomy Use of a Use of a

nasogastric tubenasogastric tube Large-volume Large-volume

gastric aspirationgastric aspiration

BurnsBurns ComaComa Head injuryHead injury Multiple organ Multiple organ

system failure system failure (MOSF)(MOSF)

Acute Acute respiratory respiratory distress distress syndrome syndrome (ARDS)(ARDS)

Duration of Duration of mechanical mechanical ventilationventilation

Intracuff Intracuff pressure pressure <20 cm H<20 cm H2200

ReintubationReintubation

(Mehta RM. J Intensive Care Med 2003;18:175-88) (Mehta RM. J Intensive Care Med 2003;18:175-88) (Patel PJ, et al. Seminar Respir Crit Care Med 2002;23:415-25)(Patel PJ, et al. Seminar Respir Crit Care Med 2002;23:415-25)

(American Thoracic Society. Am J Respir Crit Care Med 2005;171:388-416) (American Thoracic Society. Am J Respir Crit Care Med 2005;171:388-416)

Pathogenesis of Pathogenesis of HAP/VAPHAP/VAP

Pathogenesis of HAP/VAPPathogenesis of HAP/VAP

Pathogenesis of VAPPathogenesis of VAP

Endogenous and Exogenous SourcesEndogenous and Exogenous Sources

Causative Causative PathogensPathogens

Classification of HAP & Classification of HAP & VAP: VAP:

Risk StratificationRisk StratificationTime from Hospitalization Time from Hospitalization

(days)(days)Time from Hospitalization Time from Hospitalization

(days)(days)

Time from Intubation Time from Intubation (days)(days)

Time from Intubation Time from Intubation (days)(days)

Late-onset HAPLate-onset HAP

Early-onset VAPEarly-onset VAP Late-onset VAP Late-onset VAP

Early-onset HAPEarly-onset HAP

0000 1111 2222 3333 4444 5555 6666 7777

0000 1111 2222 3333 4444 5555 6666 7777

(American Thoracic Society. Am J Respir Crit Care Med 2005;171:388-416)(American Thoracic Society. Am J Respir Crit Care Med 2005;171:388-416)

Pathogens to Consider Pathogens to Consider When Treating HAP/VAPWhen Treating HAP/VAP

Early HAP/VAPEarly HAP/VAP Late HAP/VAPLate HAP/VAP

TimingTiming Within five days of Within five days of admission or mechanical admission or mechanical ventilationventilation

Five days or more after Five days or more after admission or mechanical admission or mechanical ventilation ventilation

BacteriologBacteriology y

S. pneumoniae S. pneumoniae

H. influenzaeH. influenzae

Methicillin-sensitive Methicillin-sensitive S. S. aureusaureus

Susceptible gram-negative Susceptible gram-negative bacteriabacteria

P. aeruginosaP. aeruginosa

AcinetobacterAcinetobacter

Methicillin-resistant Methicillin-resistant S. aureusS. aureus

Other multi-resistant Other multi-resistant organismsorganisms

Prognosis Prognosis Less severe, little impact Less severe, little impact on outcome on outcome

Mortality minimalMortality minimal

Higher attributable mortality Higher attributable mortality and morbidity and morbidity

(American Thoracic Society/IDSA. Am J Respir Crit Care Med (American Thoracic Society/IDSA. Am J Respir Crit Care Med 2005;171:388-416)2005;171:388-416)

Frequency of bacterial pathogens in HAP in Frequency of bacterial pathogens in HAP in North America: 2,712 strains (SENTRY, North America: 2,712 strains (SENTRY, Antimicrobial Surveillance Program, Jan.-Antimicrobial Surveillance Program, Jan.-June 2000)June 2000)

RankRank OrganismOrganism No. of isolates (%)No. of isolates (%)

11 S. aureusS. aureus 760 (28.0) – (43.7% 760 (28.0) – (43.7% MRSA)MRSA)

22 P. aeruginosaP. aeruginosa 543 (20.0)543 (20.0)

33 S. pneumoniaeS. pneumoniae 246 (9.1)246 (9.1)

44 Klebsiella spp.Klebsiella spp. 203 (7.5)203 (7.5)

55 H. influenzaeH. influenzae 199 (7.3)199 (7.3)

66 Enterobacter spp.Enterobacter spp. 156 (5.8)156 (5.8)

77 E. coliE. coli 105 (3.9)105 (3.9)

88 Serratia spp.Serratia spp. 96 (3.5)96 (3.5)

99 S. maltophiliaS. maltophilia 94 (3.5)94 (3.5)

(Hoban DJ et al. Diag Microbiol Infect Dis 2003;45:279-285)(Hoban DJ et al. Diag Microbiol Infect Dis 2003;45:279-285)

Microbiology of Ventilator-Associated Pneumonia at Three Microbiology of Ventilator-Associated Pneumonia at Three Barnes-Jewish Christian HealthCare Hospitals (Teaching, Barnes-Jewish Christian HealthCare Hospitals (Teaching, Community & Pediatric), 1998-2001 (N=753 Episodes)Community & Pediatric), 1998-2001 (N=753 Episodes)

No. of Infections Associated With No. of Infections Associated With Organism(%)Organism(%)

OrganismOrganism

IdentifiedIdentifiedEarly VAP*Early VAP*

(n=137)(n=137)Late VAP*Late VAP*

(n=616)(n=616) TotalTotal

Pseudomonas Pseudomonas aeruginosaaeruginosa

22 (16)22 (16) 168 (27.3)168 (27.3) 190 (25.2)190 (25.2)

Methicillin-sensitiveMethicillin-sensitive

Staphylococcus Staphylococcus aureusaureus

30 (21.9)30 (21.9) 106 (17.2)106 (17.2) 136 (18.1)136 (18.1)

Methicillin-resistant Methicillin-resistant Staphylococcus Staphylococcus aureusaureus

11 (8)11 (8) 67 (10.9)67 (10.9) 78 (10.3)78 (10.3)

Enterobacter cloacaeEnterobacter cloacae 4 (2.9)4 (2.9) 43 (7)43 (7) 47 (6.2)47 (6.2)

Acinetobacter Acinetobacter baumanniibaumannii

4 (2.9)4 (2.9) 40 (6.5)40 (6.5) 44 (5.8)44 (5.8)

Klebsiella Klebsiella pneumoniaepneumoniae

3(2.2)3(2.2) 40 (6.5)40 (6.5) 43 (5.7)43 (5.7)

Serratia marcescensSerratia marcescens 6 (4.4)6 (4.4) 30 (4.9)30 (4.9) 36 (4.7)36 (4.7)

Stenotrophomonas Stenotrophomonas maltophiliamaltophilia

5(3.6)5(3.6) 27 (4.4)27 (4.4) 32 (4.2)32 (4.2)

VAP-ventilator-associated pneumoniaVAP-ventilator-associated pneumonia

*Early VAP-within 4 days of intubation; late VAP-after 5 or more days of mechanical *Early VAP-within 4 days of intubation; late VAP-after 5 or more days of mechanical ventilationventilation

(Babcock HM et al. Infect Control Hosp Epidemiol 2003;24:853-858)(Babcock HM et al. Infect Control Hosp Epidemiol 2003;24:853-858)

Diagnosis of HAPDiagnosis of HAP

Diagnosis of HAP/VAPDiagnosis of HAP/VAP

Clinical approachClinical approach

Vs.Vs.

Invasive approachInvasive approach

Non-invasive Strategy for Non-invasive Strategy for Diagnosing HAP/VAPDiagnosing HAP/VAP

Clinical approach:Clinical approach: New lung infiltrateNew lung infiltrate

new onset fever, leukocytosis or purulent new onset fever, leukocytosis or purulent sputumsputum

non-quantitative bacterial analysis of non-quantitative bacterial analysis of endotracheal aspirateendotracheal aspirate

Drawback Drawback –– relatively non-specific for HAP relatively non-specific for HAP Heyland et al. demonstrated adequacy of clinical Heyland et al. demonstrated adequacy of clinical

criteria for VAP diagnosis in RCT (BAL with criteria for VAP diagnosis in RCT (BAL with quantitation vs. non-quantitative endotracheal quantitation vs. non-quantitative endotracheal aspirate): no difference in 28 d mortality or LOS aspirate): no difference in 28 d mortality or LOS in ICU or hospital in ICU or hospital

(ATS, Am J Respir Crit Care Med 1996;153:1711-1725)(ATS, Am J Respir Crit Care Med 1996;153:1711-1725)

(Helling TS, Van Way C, Krantz S, et al. Am J Surg 1996;171:570-575)(Helling TS, Van Way C, Krantz S, et al. Am J Surg 1996;171:570-575)

(Hubmayr RD et al ATS Consensus Statement Intensive Care Med 2002;28:1521-(Hubmayr RD et al ATS Consensus Statement Intensive Care Med 2002;28:1521-1536)1536)

(Canadian Critical Care Trials Group. NEJM 2006;355:2619-2630)(Canadian Critical Care Trials Group. NEJM 2006;355:2619-2630)

0

10

20

30

40

50

60

70

80

28dMortality

TargetedTherapy

DaysWithout

Antibiotics

OrganDysfunction

Score

LOS in ICU

BALETA

Diagnosis of VAP in the ICU:Diagnosis of VAP in the ICU:Quantitative BAL vs. Nonquantitative Quantitative BAL vs. Nonquantitative

Endotracheal Aspirate (ETA)Endotracheal Aspirate (ETA)

PrimaryPrimaryOutcomOutcom

ee

Secondary OutcomesSecondary Outcomes

Resp

on

se

Resp

on

se

18.9%18.9%18.4% *18.4% *

74.2%74.2% 74.6%*74.6%*

10.4d10.4d 10.6d*10.6d* 12.3d12.3d 12.2d*12.2d*8.38.3 8.6*8.6*

(Canadian Critical Care Trials Group. NEJM 2006;355:2619-2630)(Canadian Critical Care Trials Group. NEJM 2006;355:2619-2630)

* = NS* = NS

Non-invasive Strategy for Non-invasive Strategy for Diagnosing HAP/VAPDiagnosing HAP/VAP

Clinical approach:Clinical approach: CPIS – clinical pulmonary infection scoreCPIS – clinical pulmonary infection score

Quantitative prediction model using clinical criteriaQuantitative prediction model using clinical criteria May improve clinical diagnosis of HAPMay improve clinical diagnosis of HAP

72%-85% sensitive, 85%-91% specific72%-85% sensitive, 85%-91% specific Only validated in several small studiesOnly validated in several small studies

(Pugin J, Auckenthaler R, Mili N, et al. Am Rev Respir Dis 1991;143:1121-1129)(Pugin J, Auckenthaler R, Mili N, et al. Am Rev Respir Dis 1991;143:1121-1129)

(Hubmayr RD et al ATS Consensus Statement Intensive Care Med 2002;28:1521-(Hubmayr RD et al ATS Consensus Statement Intensive Care Med 2002;28:1521-1536)1536)

Short Course Therapy of Short Course Therapy of Suspected VAP Using the Suspected VAP Using the

CPISCPIS

RX 10-21 DAYS

CPIS > 6

RX

DAY 3 CPIS > 6

D/C RX

DAY 3 CPIS < or =6

CIPRO 3D STANDARD RX

CPIS < or =6:RANDOMIZE

CPIS ON DX

CPIS on diagnosis with 5 criteria: fever, WBC, trach secretions, oxygen, CPIS on diagnosis with 5 criteria: fever, WBC, trach secretions, oxygen, X-ray. X-ray.

CPIS on day 3 with 7 criteria: add x-ray progression, culture data.CPIS on day 3 with 7 criteria: add x-ray progression, culture data.

(Singh N et al. AJRCCM 2000;162:505-511)(Singh N et al. AJRCCM 2000;162:505-511)

Invasive Strategy for Invasive Strategy for Diagnosing HAPDiagnosing HAP

Quantitative culture approach:Quantitative culture approach: bronchoscopic protected specimen brush (≥10bronchoscopic protected specimen brush (≥1033

CFU/ml)CFU/ml) ~67% sensitive, 95% specific~67% sensitive, 95% specific

bronchoalveolar lavage (≥10bronchoalveolar lavage (≥1044 CFU/ml) CFU/ml) ~73% sensitive, 82% specific~73% sensitive, 82% specific

quantitative endotracheal aspirate (≥10quantitative endotracheal aspirate (≥1055 CFU/ml)CFU/ml)

38-100% sensitive, 14-100% specific38-100% sensitive, 14-100% specific Antibiotic use more appropriate and accurate Antibiotic use more appropriate and accurate Claim of improved survival at 28 days Claim of improved survival at 28 days

(Fagon JY, Chastre J, Wolff M, et al. Ann Intern Med 2000;132:621-630)(Fagon JY, Chastre J, Wolff M, et al. Ann Intern Med 2000;132:621-630)

(Craven DE, and Steger KA, et al. Infect Cont Hosp Epidemiol 1997;18:783-795)(Craven DE, and Steger KA, et al. Infect Cont Hosp Epidemiol 1997;18:783-795)

(Grossman RF and Fein A. Chest 2000;117:177S-181S)(Grossman RF and Fein A. Chest 2000;117:177S-181S)

(Shorr Crit Care Med 2005;33:46-53)(Shorr Crit Care Med 2005;33:46-53)

Meta-analysis of Meta-analysis of Bronchoscopy:Bronchoscopy:

MortalityMortality

Patient Patient on wardon ward

Clinical Clinical features features suggest suggest infectioninfection

??

Order/review recent Order/review recent chest roentgenogramchest roentgenogram

Abnormal Abnormal ??

No further No further investigatioinvestigation/observen/observe

Observe:Observe:Investigate for Investigate for other sources other sources

NoNo

NoNo

YesYes

Figure 1 Diagnostic Algorithm for Figure 1 Diagnostic Algorithm for HAPHAP

YesYes

CPIS ≤ 6CPIS ≤ 6 CPIS > 6CPIS > 6

Consider therapyConsider therapy

Gram stain Gram stain tracheobronchial tracheobronchial

secretions: if pus cells secretions: if pus cells & organisms present & organisms present

(Yes)(Yes)

Calculate Calculate CPISCPIS

Treat according to Treat according to Gram stain and Gram stain and local epidemiologylocal epidemiology

Recalculate CPIS Recalculate CPIS daily; examine daily; examine Gram stain;Gram stain;

Stop therapy if Stop therapy if CPIS CPIS 6 on day 36 on day 3

Figure 1 (cont’d)Figure 1 (cont’d)Diagnostic Algorithm for HAPDiagnostic Algorithm for HAP

No pus No pus cells or cells or organismorganismss

Figure 2Figure 2Diagnostic Algorithm for VAPDiagnostic Algorithm for VAP

Mechanically Mechanically ventilatedventilated patientpatient

Clinical Clinical features features suggest suggest infectioninfection

??

Order/review recent Order/review recent chest chest

roentgenogramroentgenogram

Abnormal?Abnormal?

No further No further investigatiinvestigation/observeon/observe

Observe:Observe:Investigate for Investigate for other sources other sources

YesYes

NoNo

YesYes

CPIS ≤ 6CPIS ≤ 6 CPIS > 6CPIS > 6

CPIS ≥ 4CPIS ≥ 4CPIS < 4CPIS < 4 Gram stain Gram stain

tracheobronchial tracheobronchial secretions: Yes secretions: Yes

organisms & pus organisms & pus cells presentcells presentStop therapy if Stop therapy if

startedstarted

Calculate Calculate CPISCPIS

Consider Consider therapy and no therapy and no alternate alternate diagnosisdiagnosis

Treat Treat according to according to Gram stain Gram stain and local and local epidemiologyepidemiology

Recalculate CPIS daily; Recalculate CPIS daily; examine Gram stain;examine Gram stain;Stop therapy after 3 Stop therapy after 3 days if CPIS days if CPIS 66

Figure 2 (cont’)Figure 2 (cont’)Diagnostic Algorithm for VAPDiagnostic Algorithm for VAP

NONO

Initial Therapy of Initial Therapy of HAP/VAPHAP/VAP

The Importance of Initial The Importance of Initial Empiric Antibiotic Empiric Antibiotic

SelectionSelection

16.2

41.5 3833.3

1524.7

63

81

61.4

44

0102030405060708090

Alvarez-Lerma

Rello Luna Kollef Clec'h

% m

ort

ali

ty

Adequate init. antibiotic Inadequate init. antibiotic

(Alvarez-Lerma F. Intensive Care Med 1996;22:387-94) (Alvarez-Lerma F. Intensive Care Med 1996;22:387-94)

(Rello J, Gallego M, Mariscal D, et al. Am J Respir Crit Care Med (Rello J, Gallego M, Mariscal D, et al. Am J Respir Crit Care Med 1997;156:196-200)1997;156:196-200)

(Luna CM, Vujacich P, Niederman MS et al. Chest 1997;111:676-685)(Luna CM, Vujacich P, Niederman MS et al. Chest 1997;111:676-685)

(Kollef MH and Ward S. (Kollef MH and Ward S. ChestChest 1998;113:412-20) 1998;113:412-20)

p <.05p <.05**** ** ** **

(Clec’h C, Timsit J-F, De Lassence A et al. Intensive Care Med 2004;30:1327-1333)(Clec’h C, Timsit J-F, De Lassence A et al. Intensive Care Med 2004;30:1327-1333)

Figure 1.Figure 1.Initial Empiric Antibiotic Therapy of HAPInitial Empiric Antibiotic Therapy of HAP

Diagnosis of Diagnosis of HAP HAP

Mild-Moderate Mild-Moderate PresentationPresentationGroup 1Group 1

Mild-Moderate Mild-Moderate Presentation Presentation + Risk Factors+ Risk Factorsfor Resistancefor ResistanceGroup 2Group 2

Severe Severe PresentatiPresentationonGroup 3Group 3

Treat on Treat on Ward with Ward with

IV/Oral IV/Oral MonotheraMonotherapy for Core py for Core Pathogens Pathogens

for 7-8 daysfor 7-8 days

Treat on Ward Treat on Ward with IV/Oral with IV/Oral

Monotherapy for Monotherapy for Core Pathogens Core Pathogens

and Possible and Possible Resistant Resistant

Pathogens for 7-8 Pathogens for 7-8 days days

Treat in ICU Treat in ICU with IV with IV

Combination Combination Therapy *IV Therapy *IV

InitiallyInitially

Streamline Streamline Therapy Based Therapy Based

on Culture on Culture ResultsResults

Modify Modify Treatment if Treatment if

Resistant Resistant Pathogens Pathogens

PresentPresent

*Resistant Pathogens such as:*Resistant Pathogens such as:P. aeruginosa, Acinetobacter P. aeruginosa, Acinetobacter spp., S. maltophiliaspp., S. maltophilia and MRSA and MRSA may require longer durations may require longer durations of treatment (14 da) of treatment (14 da)

Streamline Streamline Therapy Based Therapy Based

on Culture on Culture ResultsResults

Figure 2.Figure 2.Initial Empiric Antibiotic Therapy of VAPInitial Empiric Antibiotic Therapy of VAP

Diagnosis Diagnosis of VAP in of VAP in

ICUICU

Moderate Moderate PresentationPresentationGroup 4Group 4

Severe Severe Presentation Presentation and/or Risk and/or Risk Factors for Factors for ResistanceResistanceGroup 5Group 5

Treat in ICU Treat in ICU with IV with IV

Monotherapy Monotherapy for 7-8 Daysfor 7-8 Days

Treat in ICU Treat in ICU with with

Combination Combination Therapy* IV Therapy* IV

InitiallyInitially

Streamline Therapy Streamline Therapy Based on Culture Based on Culture

Results Results (Monotherapy IV (Monotherapy IV

may be appropriate may be appropriate for 7-8 days)for 7-8 days)

*Resistant Pathogens such as:*Resistant Pathogens such as:P. aeruginosa, Acinetobacter spp., S. maltophiliaP. aeruginosa, Acinetobacter spp., S. maltophilia and and MRSA may require longer durations of treatment (14 MRSA may require longer durations of treatment (14 da) da)

Streamline Streamline Therapy Based Therapy Based

on Culture on Culture ResultsResults

  

*mild-moderate presentation: no hypotension, intubation, sepsis syndrome, rapid *mild-moderate presentation: no hypotension, intubation, sepsis syndrome, rapid progression of infiltrates or multiple organ dysfunction.progression of infiltrates or multiple organ dysfunction.

HAP: Group 1 – Mild-Moderate Presentation*, HAP: Group 1 – Mild-Moderate Presentation*, Early Onset (< 5 days), and No Risk Factors for Early Onset (< 5 days), and No Risk Factors for Resistance. Resistance.   

Potential PathogensPotential Pathogens

Streptococcus pneumoniae Streptococcus pneumoniae

Streptococcus spp.Streptococcus spp.

Methicillin-susceptibleMethicillin-susceptible

Staphylococcus aureusStaphylococcus aureus

Haemophilus influenzaeHaemophilus influenzae

EnterobacteriaeceaeEnterobacteriaeceae

Escherichia coliEscherichia coli

Klebsiella pneumoniaeKlebsiella pneumoniae

Enterobacter spp.Enterobacter spp.

Proteus spp.Proteus spp.

Serratia spp.Serratia spp.

Treatment of HAP: Group Treatment of HAP: Group 11

No risk factors for resistance+ mild-moderate No risk factors for resistance+ mild-moderate presentation presentation

Treatment:Treatment:

33rdrd generation non-pseudomonal cephalosporin generation non-pseudomonal cephalosporin

(eg. ceftriaxone 1 g q24h IV, cefotaxime 1 g q8h IV)(eg. ceftriaxone 1 g q24h IV, cefotaxime 1 g q8h IV)

or 4or 4thth generation cephalosporin (cefepime 1-2g generation cephalosporin (cefepime 1-2g q12h IV)q12h IV)

OROR

beta-lactam/beta-lactamase inhibitorbeta-lactam/beta-lactamase inhibitor

(eg. piperacillin-tazobactam 4.5 g q8h IV)(eg. piperacillin-tazobactam 4.5 g q8h IV)

OROR

fluoroquinolone (levofloxacin 750 mg IV qd or fluoroquinolone (levofloxacin 750 mg IV qd or moxifloxacin 400 mg IV qd) moxifloxacin 400 mg IV qd) po po

HAP: Group 2- Mild-Moderate Presentation, HAP: Group 2- Mild-Moderate Presentation, and Risk Factors for Resistance (Prior and Risk Factors for Resistance (Prior Antimicrobial Therapy in Preceding 90 days Antimicrobial Therapy in Preceding 90 days and/or Hospitalization for and/or Hospitalization for >> 5 days). 5 days).

Potential PathogensPotential Pathogens

  

Haemophilus influenzaeHaemophilus influenzae

EnterobacteriaeceaeEnterobacteriaeceae

E. coliE. coli

K. pneumoniaeK. pneumoniae

Enterobacter spp.Enterobacter spp.

Proteus spp.Proteus spp.

Serratia spp.Serratia spp.

Pseudomonas aeruginosaPseudomonas aeruginosa

Streptococcus pneumoniaeStreptococcus pneumoniae

Methicillin-susceptible and –resistant Methicillin-susceptible and –resistant S. aureusS. aureus

Treatment of HAP: Group Treatment of HAP: Group 22

Risk factors for resistance, and/or late onset + Risk factors for resistance, and/or late onset + mild-moderate presentation (Cont’d)mild-moderate presentation (Cont’d)

Treatment:Treatment:3rd generation non-pseudomonal cephalosporin (eg. 3rd generation non-pseudomonal cephalosporin (eg. ceftriaxone 1 g q24h IV, cefotaxime 1 g q8h IV) or 4ceftriaxone 1 g q24h IV, cefotaxime 1 g q8h IV) or 4thth generation cephalosporin (cefepime 1-2 g q12h IV) generation cephalosporin (cefepime 1-2 g q12h IV)

ORORpiperacillin-tazobactam 4.5 g q8h IVpiperacillin-tazobactam 4.5 g q8h IV

ORORimipenem 500 mg q6h IV imipenem 500 mg q6h IV

ORORmeropenem 500 mg q6h IVmeropenem 500 mg q6h IV

ORORlevofloxacin 750 mg q24h IVlevofloxacin 750 mg q24h IV

OROR moxifloxacin 400 mg q24h IVmoxifloxacin 400 mg q24h IV +/- +/-

vancomycin 1 g q12h IV or linezolid 600 mg q12h IVvancomycin 1 g q12h IV or linezolid 600 mg q12h IV

Treatment of HAP: Group 2 Treatment of HAP: Group 2 (cont’d)(cont’d)

Risk factors for resistance, and/or late onset (Risk factors for resistance, and/or late onset (≥ 5 days)≥ 5 days)+ mild-moderate presentation (Cont’d)+ mild-moderate presentation (Cont’d)

Treatment (cont’d):Treatment (cont’d):

For suspected For suspected P. aeruginosaP. aeruginosa : :beta-lactam/beta-lactamase inhibitor (piperacillin-beta-lactam/beta-lactamase inhibitor (piperacillin-tazobactam 4.5 g q6h IV)tazobactam 4.5 g q6h IV)

or or antipseudomonal cephalosporin (ceftazidime or antipseudomonal cephalosporin (ceftazidime or cefepime 2 g q8h IV) cefepime 2 g q8h IV)

or or carbapenem (imipenem or meropenem 1 g q8h IV)carbapenem (imipenem or meropenem 1 g q8h IV)

plus plus fluoroquinolone (ciprofloxacin 400 mg q8h IV or 750 mg fluoroquinolone (ciprofloxacin 400 mg q8h IV or 750 mg BID po or levofloxacin 750 mg q24h IV/po)BID po or levofloxacin 750 mg q24h IV/po)

or or aminoglycoside (gentamicin or tobramycin 5-7 mg/kg aminoglycoside (gentamicin or tobramycin 5-7 mg/kg q24h IV or amikacin 15-20 mg/kg q24h IV)q24h IV or amikacin 15-20 mg/kg q24h IV)

HAP: Group 3- Severe Presentation, &/or Risk HAP: Group 3- Severe Presentation, &/or Risk Factors for Resistance (Prior Antimicrobial Factors for Resistance (Prior Antimicrobial Therapy in Preceding 90 days and/or Therapy in Preceding 90 days and/or Hospitalization for Hospitalization for >> 5 days) 5 days)

Potential PathogensPotential Pathogens

  

Haemophilus influenzaeHaemophilus influenzae

EnterobacteriaeceaeEnterobacteriaeceae

E. coliE. coli

K. pneumoniaeK. pneumoniae

Enterobacter spp.Enterobacter spp.

Proteus spp.Proteus spp.

Serratia spp.Serratia spp.

Pseudomonas aeruginosaPseudomonas aeruginosa

Streptococcus pneumoniaeStreptococcus pneumoniae

Methicillin-susceptible and –resistant Methicillin-susceptible and –resistant S. aureusS. aureus

HAP: Group 3-Severe Presentation (Hypotension, HAP: Group 3-Severe Presentation (Hypotension, Need for Intubation, Sepsis Syndrome, Rapid Need for Intubation, Sepsis Syndrome, Rapid Progression of Infiltrates or End Organ Dysfunction) Progression of Infiltrates or End Organ Dysfunction) and/or Risk for Resistanceand/or Risk for Resistance

Treatment:Treatment: Treat with combination therapy:Treat with combination therapy: anti-pseudomonal cephalosporin (ceftazidime or cefepime 2 g anti-pseudomonal cephalosporin (ceftazidime or cefepime 2 g

q8h IV) q8h IV) or or beta-lactam/beta-lactamase inhibitor (piperacillin-tazobactam beta-lactam/beta-lactamase inhibitor (piperacillin-tazobactam 4.5 g q6h IV) 4.5 g q6h IV) or or carbapenem (imipenem or meropenem 1g q8h IV or 1 g q8h IV) carbapenem (imipenem or meropenem 1g q8h IV or 1 g q8h IV) plusplus fluoroquinolone (ciprofloxacin 400 mg q8h IV or levofloxacin fluoroquinolone (ciprofloxacin 400 mg q8h IV or levofloxacin

750 mg q24h IV) 750 mg q24h IV) or or aminoglycoside (gentamicin or tobramycin 5-7mg/kg qd IV or aminoglycoside (gentamicin or tobramycin 5-7mg/kg qd IV or

amikacin 15-20 mg/kg qd IV) amikacin 15-20 mg/kg qd IV) +/- +/- vancomycin 1 g q12 h IV or linezolid 600 mg q12 h IV if MRSA vancomycin 1 g q12 h IV or linezolid 600 mg q12 h IV if MRSA

present or suspectedpresent or suspected

VAP: Group 4-Moderate Presentation, No Risk VAP: Group 4-Moderate Presentation, No Risk Factors for Resistance and Early Onset < 5 Factors for Resistance and Early Onset < 5 days.days.

Potential PathogensPotential Pathogens

S. pneumoniae S. pneumoniae

Methicillin-susceptible Methicillin-susceptible S. aureusS. aureus

H. influenzaeH. influenzae

EnterobacteriaeceaeEnterobacteriaeceae

E. coliE. coli

Klebsiella spp.Klebsiella spp.

Enterobacter spp.Enterobacter spp.

Proteus spp.Proteus spp.

Serratia spp.Serratia spp.

Treatment of VAP: Group Treatment of VAP: Group 44

No risk factors for resistance, early onset (<5 days No risk factors for resistance, early onset (<5 days of hospitalization) & moderate presentationof hospitalization) & moderate presentation

Treatment:Treatment: 33rdrd generation non-pseudomonal generation non-pseudomonal

cephalosporincephalosporin(eg. ceftriaxone 1 g q24h IV, cefotaxime 1 g (eg. ceftriaxone 1 g q24h IV, cefotaxime 1 g

q8h IV)q8h IV)or 4or 4thth generation cephalosporin (cefepime 2 generation cephalosporin (cefepime 2

g q12h g q12h IV)IV) OROR

beta-lactam/beta-lactamase inhibitorbeta-lactam/beta-lactamase inhibitor(eg. piperacillin-tazobactam 4.5 g q6h IV)(eg. piperacillin-tazobactam 4.5 g q6h IV)

ORORfluoroquinolone (levofloxacin 750 mg IV qd, fluoroquinolone (levofloxacin 750 mg IV qd,

moxifloxacin 400 mg IV qd] moxifloxacin 400 mg IV qd] po po

Therapy of VAP: Group 5Therapy of VAP: Group 5

Group 5 Risk factors for antimicrobial Group 5 Risk factors for antimicrobial resistance present, late onset and/or resistance present, late onset and/or severe presentationsevere presentation

Risk factors for antimicrobial resistance present:Risk factors for antimicrobial resistance present: - Prolonged hospitalization- Prolonged hospitalization - Prior hospital antimicrobial - Prior hospital antimicrobial

therapy within 90 d therapy within 90 d - ICU stay - ICU stay 5 days 5 days - Structural lung disease- Structural lung disease

- P. aeruginosa or Acinetobacter spp- P. aeruginosa or Acinetobacter spp..

Severe presentation - hypotension, intubation, Severe presentation - hypotension, intubation, severe sepsis, rapid progression of infiltrates or severe sepsis, rapid progression of infiltrates or organ dysfunctionorgan dysfunction

VAP: Group 5-Severe Presentation, VAP: Group 5-Severe Presentation, Risk Factors for Antimicrobial Risk Factors for Antimicrobial Resistance, and/or Late Onset Resistance, and/or Late Onset >> 5 Days 5 Days

Potential PathogensPotential Pathogens

Methicillin-susceptibleMethicillin-susceptible S. aureus S. aureus

EnterobacteriaeceaeEnterobacteriaeceae

E. coliE. coli

K. pneumoniaeK. pneumoniae

Proteus spp.Proteus spp.

Serratia spp.Serratia spp.

P. aeruginosaP. aeruginosa

Acinetobacter spp.Acinetobacter spp.

Methicillin-resistant Methicillin-resistant S. aureusS. aureus

S. pneumoniaeS. pneumoniae

Treatment of VAP: Group Treatment of VAP: Group 55

Risk factors for resistance present +/- severe Risk factors for resistance present +/- severe presentation (Cont’d)presentation (Cont’d)

Treatment:Treatment: ceftazidime 2 g q8h IV or cefepime 2g q8h IVceftazidime 2 g q8h IV or cefepime 2g q8h IV

OROR imipenem-cilastatin 1 g q8h IVimipenem-cilastatin 1 g q8h IV

OROR meropenem 1 g q8h IV meropenem 1 g q8h IV

OROR piperacillin-tazobactam 4.5 g q6h IV piperacillin-tazobactam 4.5 g q6h IV

PLUSPLUS ciprofloxacin 400 mg q8h IV or levofloxacin 750 mg q24h IVciprofloxacin 400 mg q8h IV or levofloxacin 750 mg q24h IV

OROR gentamicin or tobramycin 5-7 mg/kg q24h IV or amikacin gentamicin or tobramycin 5-7 mg/kg q24h IV or amikacin

15-20 mg/kg q24h IV 15-20 mg/kg q24h IV +/- +/- vancomycin 1 g q12h IV or linezolid 600 mg q12h IVvancomycin 1 g q12h IV or linezolid 600 mg q12h IV

Short Course Therapy of Short Course Therapy of Suspected VAP Using the Suspected VAP Using the

CPISCPIS

RX 10-21 DAYS

CPIS > 6

RX

DAY 3 CPIS > 6

D/C RX

DAY 3 CPIS < or =6

CIPRO 3D STANDARD RX

CPIS < or =6:RANDOMIZE

CPIS ON DX

CPIS on diagnosis with 5 criteria: fever, WBC, trach secretions, oxygen, CPIS on diagnosis with 5 criteria: fever, WBC, trach secretions, oxygen, X-ray. X-ray.

CPIS on day 3 with 7 criteria: add x-ray progression, culture data.CPIS on day 3 with 7 criteria: add x-ray progression, culture data.

(Singh N et al. AJRCCM 2000;162:505-511)(Singh N et al. AJRCCM 2000;162:505-511)

VAP: 8 Day vs. 15 Day Antibiotic VAP: 8 Day vs. 15 Day Antibiotic Therapy – Shorter may be BetterTherapy – Shorter may be Better

0

10

20

30

40

50

60

70

80

Mortality Lung InfectionRecurrence

BSA Free days NFGN Infections UnfavorableOutcome MRSA

8 Day Treatment

15 Day Treatment

% or

Days

% or

Days

Primary OutcomesPrimary Outcomes

(Chastre J et al. JAMA 2003;290:2588-(Chastre J et al. JAMA 2003;290:2588-2598)2598)

18.4 d18.4 d15.3 d15.3 d

*P=.01*P=.01

18.818.8 17.217.2

28.928.9 2626

40.640.6

28.928.9

57.157.1

76.276.2

SummarySummary Clinical diagnostic criteriaClinical diagnostic criteria more adaptable more adaptable

to the Canadian clinical environment.to the Canadian clinical environment. Appropriateness of therapyAppropriateness of therapy important in important in

treatment of HAP.treatment of HAP. In VAP, appropriateness and early In VAP, appropriateness and early

initiation ofinitiation of antimicrobial therapyantimicrobial therapy particularly important. particularly important.

Severity of illness and risk for resistance Severity of illness and risk for resistance determinedetermine initial initial antimicrobial selection.antimicrobial selection.

7 or 8 days of therapy7 or 8 days of therapy may suffice for most may suffice for most cases of HAP & VAP; but cases of HAP & VAP; but 14 days preferred 14 days preferred forfor P. aeruginosaP. aeruginosa & & Acinetobacter spp.Acinetobacter spp.