New Optional for Treatmen Gram Positive Infection 1

8/3/2019 New Optional for Treatmen Gram Positive Infection 1

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Herdiman T Pohan

Division of Infectious and Tropical Diseases

Department of Internal Medicine Faculty of Medicine

University of Indonesia, Jakarta

New Optional for Gram (+)New Optional for Gram (+)

InfectionInfection TreatmentTreatment


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Gram (+) Coccus :- Staphylococcus Aureus

- Coagulase-negative Staphylococcus aureus

- F Hemoliticus Streptococcus : Group A- F Hemoliticus Staphylococcus : Group B

- Enterococcus

- Pneumococcus

- Anaerobes Streptococcus- MRSA, GISA, GRSA ,VRE, PRSP


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Incidence of Gram-positive Infections

Atrisk patients populations:Susceptible host and Imunocompromised Pts.

Change among gram (+) :

Coagulase-negative staphylococcus pathogens

Group A Streptococcus group B streptococcus

Penicilin-resistantPneumococcus

Enterococcus faecalis


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Various Clinical Infections Involving

Gram-positive Bacterial- Sepsis/Bacteremia

- Respiratory tract infections

- Urinary tract infections

- Bone and joint infections

- Endocarditis

- Febrile Neutropenia

- Gastrointestinal infections

- Skin and soft tissue infections


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Staphylococci AssociatedStaphylococci Associatedwith Human Diseasewith Human Disease

S.S. aureusaureus

S.S. epidermidisepidermidis

S.S. saprophyticussaprophyticus


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Caused by Staphylococcus spp.Caused by Staphylococcus spp.

OrganismOrganism Carrier Carrier Infections InfectionsCoagulatedCoagulated--

positivepositive

staphylococcistaphylococci

((S. aureusS. aureus))

SkinSkin

NasopharynxNasopharynx

VaginaVagina

SkinSkin : folliculitis, impetigo, furuncles, cellulitis,: folliculitis, impetigo, furuncles, cellulitis,

carbuncles, postoperative wound infectionscarbuncles, postoperative wound infections

Deep InfectionsDeep Infections : endocarditis, meningitis,: endocarditis, meningitis,

arthritis, pneumonia, osteomyelitis, pyomyositis,arthritis, pneumonia, osteomyelitis, pyomyositis,

sepsis, and multiple organ failure.sepsis, and multiple organ failure.

ToxinToxin--mediated diseasemediated disease : food poisoning,: food poisoning,

scalded skin syndrome, toxic shock syndrome.scalded skin syndrome, toxic shock syndrome.

CoagulaseCoagulase--

negativenegative

staphylococcistaphylococci

((S. epidermidisS. epidermidis

and others)and others)

Skin Ear canalSkin Ear canal

Genitourinary tractGenitourinary tract

Indwelling foreign bodies infectionsIndwelling foreign bodies infections : prosthetic cardiac: prosthetic cardiac

valves, permanent pacemaker wires and electrodes,valves, permanent pacemaker wires and electrodes,

vascular grafts, cerebrospinal fluid shunts, peritonealvascular grafts, cerebrospinal fluid shunts, peritoneal

dialysis catheters, prosthetic joints, intravenousdialysis catheters, prosthetic joints, intravenous

catheter.catheter.

Mucosal membranesMucosal membranes Urinary tract infectionUrinary tract infection : nosocomial (: nosocomial (S.epidermidisS.epidermidis););

outpatient women (outpatient women (S. saprophyticusS. saprophyticus).).

OtherOther : postoperative endophthalmitis,: postoperative endophthalmitis,

native valve endocarditis, osteomyelitis.native valve endocarditis, osteomyelitis.

Gates RH, Infectious Diseases Secret 2nd edition, 2003


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Emergence of Resistance BacteriaEmergence of Resistance Bacteria

in Community and Hospitalin Community and Hospital

CommunityInfections:Pneumonia Strep.pneumoniae penicillin resistant

Dysentery

Shigella

dysenteriae multiresistant

Typhoid Salmonellatyphi multiresistant

Gonorrhoea Neisseriagonorrhoeae pen & tetra resist.

Tuberculosis Mycobacteriumtuberculosis rifamp & inh resist.

Nosocomialinfections:Staph. aureus meth (& vanc) resist.

Enterococcusspp. vancomycin resistant

Klebsiella;Pseudomonas multiresistant


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MRSA/EMRSA/E

Resistant toResistant to methicillinmethicillin..

Resistant toResistant to betalactambetalactam ::Penicillin, cephalosporin,Penicillin, cephalosporin,

carbapenemcarbapenem andand betalactamasebetalactamase

inhibitor/inhibitor/betalactambetalactam combinationscombinations


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1. Available at: http://www.cdc.gov/ncidod/hip/Aresist/mrsafaq.htm.

2. Adapted from Tambyah PA et al. Infect Control Hosp Epidemiol. 2003;24:436-438.

3. Campbell AL, et al. Infect Control Hosp Epidemiol. 2003;24:427-430.

StaphylococcusStaphylococcus aureusaureus commonlycommonly carriedcarried on skin or inon skin or innose (25%nose (25%--30%)30%)11

Most MRSA infectionMost MRSA infection arisesarises in the hospital or healthcarein the hospital or healthcaresetting,setting,11--33 particularly among elderly or sick patientsparticularly among elderly or sick patients11

MRSA infectionsMRSA infections includeinclude : skin infections, bone infections,: skin infections, bone infections,pneumonia, and bloodstream infectionspneumonia, and bloodstream infections11

MRSA is almost alwaysMRSA is almost always spreadspread by direct or indirectby direct or indirectphysical contact with MRSA patientsphysical contact with MRSA patients11

EPIDEMIOLOGY OF MRSAEPIDEMIOLOGY OF MRSA


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Community Aquired MRSA

( CA-MRSA)

MRSA infection with onset in the community inan individual lacking established MRSA riskfactors1

Clinical manifestations : mild severe

Disease spectrum similar to MSSA2 :

Skin and Soft Tissue Infections (SSTIs), fromsuperficial to deeper infection

1. Fridkin SK. NEJM 2005;352(14)

2. Frazee BW. Ann Emerg Med Mar 2005;45(3)


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Community Aquired MRSA

( CA-MRSA)More severe infections:1-4

Necrotizing pneumonia Empyema Sepsis syndrome Musculoskeletal infections including pyomyositis

and osteomyelitis Necrotizing fasciitis

Purpura fulminans Disseminated infections with septic emboli

1. Gonzalez BE. Clin Infect Dis. Sep 1 2005;41(5)2. Gonzalez BE. Pediatrics. Mar 2005;115(3)3. Miller LG. NEJM 2005;352(14)

4. Adem PV. NEJM 2005;252(12)


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Patient at high risk for MRSAPatient at high risk for MRSAinfectioninfection

Tertiary care hospitalTertiary care hospital

Intensive Care Unit (ICU)Intensive Care Unit (ICU) Burn patientBurn patient

Surgical woundsSurgical wounds

IV linesIV lines


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Factor Influence MRSAFactor Influence MRSA

DurationDuration ofHospitalization.ofHospitalization.

PreviousPreviousAB treatment.AB treatment.

ProximityProximity to a patient colonized orto a patient colonized or

infected with the organism.infected with the organism.


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Methicillin-resistant Staphylococcus aureus

Nosocomial MRSA

CountryCountry Author (year)Author (year) % MRSA% MRSA

ChinaChina Li (2004)Li (2004) 81.8 %81.8 %

TaiwanTaiwan HsuehHsueh (2004)(2004) 77 %77 %

KoreaKorea Lee (2004)Lee (2004) 67 %67 %

Hsueh PR, et al. Antimicrob Agents Chemother. 2004;48:1361.Lee K, et al. Yonsei Med J. 2004;45:598.


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Percent of Staph.Percent of Staph. AureusAureus isolates inisolates in

Jakarta that resistance toJakarta that resistance to OxacillinOxacillin inin19971997 -- 19981998

TotalTotal BloodBlood PusPus

PublicPublichospitalhospital

2727 1414 2323

PrivatePrivatehospitalhospital

5757 5050 4040

Subandrio A. Pidato Pengukuhan Guru Besar FKUI 2004


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Coagulation negative staphylococciCoagulation negative staphylococci

InfectionInfection -- usualusual NosocomialNosocomial

-- S. epidermidisS. epidermidis most common :most common :associated with infected implantassociated with infected implantforeign devised :foreign devised :

Catheter, prosthetic, CSFCatheter, prosthetic, CSF

shunts, peritoneal dialysisshunts, peritoneal dialysis-- ImmunoImmuno--compromisedcompromised patientspatients


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Clinical manifestation MRSEClinical manifestation MRSE

Catheter related infections(s. epidermidis)

Cerebrospinal fluid shunt infections

(s. epidermidis, s. aureus) Peritonitis(s. epidermidis)

Endocarditis(s. epidermidis, s. aureus)

Infections in immunocompromised patients(s. epidermidis, s.aureus)

Urinary tract infection(s. saprophyticus)


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Diagnosis MRSA/E clinicallyDiagnosis MRSA/E clinically

Inadequate susceptibility to betalactam AB Typical resistant to :

aminoglycoside, chloramphenicol,

clindamycin, fluoroquinolone and macrolides


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Diagnosis laboratoryDiagnosis laboratory

Direct gram smearDirect gram smear CultureCulture

PCRPCR

Antibody to staphylococcusAntibody to staphylococcus


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Treatment of MRSATreatment of MRSA

((EmpiricalEmpirical Treatment)Treatment)

NegativeNegative culture resultsculture results

SevereSevere infection (sepsis)infection (sepsis)

Clinical profileClinical profile, prior treatment of antibiotic,, prior treatment of antibiotic,

disease progressivismdisease progressivism

Risk factorsRisk factors : length of hospital stay, ventilators,: length of hospital stay, ventilators,broad spectrum antibiotics used of cathetersbroad spectrum antibiotics used of catheters

PresencePresence of MRSA colonizationof MRSA colonization


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Six Risk Factors IndependentlySix Risk Factors Independently

Associated With MRSA InfectionAssociated With MRSA Infection

PreviousPrevious hospitalizationhospitalization

(within(within thethe lastlast1212 months)months)

LongerLonger LOSLOS beforebefore infectioninfection

SurgerySurgery

EnteralEnteral feedingsfeedings

UseUse ofof broadbroad spectrumspectrum antibioticsantibiotics

ImmunocompromisedImmunocompromised

Graffunder EM et al. J Antimicrob Chemother. 2002;49:999-1005.


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(Definite Treatment)(Definite Treatment)Based on Microbiological and susceptibility test Staph.AureusBased on Microbiological and susceptibility test Staph.Aureusresistant to methicilin or oxacillin (resistant to methicilin or oxacillin (MIC > 4 ug/mlMIC > 4 ug/ml).).

Antibiotic for MRSA :Antibiotic for MRSA :

GlycopeptideGlycopeptide : Vancomycin, Teicoplanin: Vancomycin, TeicoplaninOxazolidinonesOxazolidinones : Linezolid: LinezolidStreptograminStreptogramin : Quinopristin: Quinopristin--DalfopristinDalfopristinGycylcyclineGycylcycline : Tigecycline: TigecyclineAlternativeAlternative : Cotrimoxazole, Minocycline, Clindamycine: Cotrimoxazole, Minocycline, Clindamycine

Fluoroquinolones, Rifampicin, TetracyclineFluoroquinolones, Rifampicin, TetracyclineCombination treatmentCombination treatment: Cotrimoxazole + Rifampicin: Cotrimoxazole + Rifampicin

Minocyclin + RifampicinMinocyclin + Rifampicin

Journal of Antimicrobial Chemotherapy (2006) 57, 589-608


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Susceptibility First choice AlternativeSusceptibility First choice Alternative

Methicillin(oxacillin)Methicillin(oxacillin) VancomysinVancomysin 1g bid iv1g bid iv CotrimoxazoleCotrimoxazole 60 mg/kg/day60 mg/kg/dayresistantresistant TeicoplaninTeicoplanin 3 mg/kg (mild infection) in divide dose 23 mg/kg (mild infection) in divide dose 2--4x iv4x iv

6 mg/kg (severe infection) (960 mg bid oral)6 mg/kg (severe infection) (960 mg bid oral)12 mg/kg (endocarditis) bid iv12 mg/kg (endocarditis) bid iv MinocyclinMinocyclin (or doxycyclin)(or doxycyclin)

for the first 2for the first 2--5 day followed by 100 mg bid iv or oral5 day followed by 100 mg bid iv or oral

33--12 mg/kg qd12 mg/kg qd CiprofloxacinCiprofloxacin 400 mg bid iv400 mg bid ivLinezolidLinezolid 600 mg bid iv or oral or 500 mg bid oral600 mg bid iv or oral or 500 mg bid oralQuinopristinQuinopristin--DalfopristinDalfopristin LevofloxacinLevofloxacin 500 mg qd iv500 mg qd iv

7,5 mg/kg bid or tid iv or oral7,5 mg/kg bid or tid iv or oralTigecyclineTigecycline

Dosed 100 mg loading, 50mg everyDosed 100 mg loading, 50mg everytwelvetwelve hours,hours, ii..vv.. onlyonly

Oxacillin resistantOxacillin resistant QuinopristinQuinopristin--DalfopristinDalfopristin Vancomycin intermediate 7,5 mg/kg bid or tid Vancomycin intermediate 7,5 mg/kg bid or tid

LinezolidLinezolid 600 mg bid or oral600 mg bid or oralDosedDosed 100100 mgmg loading,loading, 5050mgmg everyeverytwelvetwelve hours,hours, ii..vv.. onlyonly

TigecyclineTigecyclineDosedDosed 100100 mgmg loading,loading, 5050mgmg everyeverytwelvetwelve hours,hours, ii..vv.. onlyonly

( MRSA )

( GRSA)


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Treatment for CA-MRSAMost CA-MRSA isolates have been susceptible

to:

Trimethoprim-sulfamethoxazole (TMP/SMX)

Gentamicin

Tetracycline (Minocycline, Doxicycline)

Clindamycin Rifampicin (use in combination)

Strategies for Clinical Management of MRSA, CDC 2006


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Treatment for severe infections

Vancomycin : as a first-line therapy

Clindamycin

Daptomycin

Linezolid

Quinopristin-dalfopristin

Tigecycline

TMP/SMX

Strategies for Clinical Management of MRSA, CDC 2006


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GlycopeptidesGlycopeptides

Emergence of resistantEmergence of resistant SS aureusaureus has led to widespread usehas led to widespread use

VancomycinVancomycin has potential limitationshas potential limitationsVREVRE is becoming a serious problemis becoming a serious problem1,21,2

VancomycinVancomycin--intermediate/resistantintermediate/resistant strains ofstrains ofSS aureusaureus have been identifiedhave been identified1,31,3

PoorPoor penetrationpenetration into lung tissueinto lung tissue44

Potential toxicitiesPotential toxicities, especially with rapid infusion, especially with rapid infusion11

TeicoplaninTeicoplanin also has potential limitationsalso has potential limitations GlycopeptideGlycopeptide--intermediateintermediate SS aureusaureus have been identifiedhave been identified33

PotentialPotential crosscross--resistanceresistance withwith EnterococcusEnterococcus sppspp11

1. Fekety R. In: Principles and Practice of Infectious Disease. 5th ed. 2000:382-392.2. Moellering RC. Clin Infect Dis. 1998;26:1196-1199.

3. Fridkin SK. Clin Infect Dis. 2001;32:108-115.

4. Cruciani M et al. J Antimicrob Chemother. 1996;38:865-869.


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*

*

***

**

P


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The use of Glycopeptide

In empirical treatment of :

IV catheter infection in neonates Patients with burns in units with high MRSA

prevalence Severe vascular catheter-related sepsis where the

catheter can not be removed and the patient ishemodynamically unstable

Prosthetic valve endocarditis

Foreign body or post-surgical meningitis withinconclusive investigation

Gemmel CG, Edwards DI, Fraise AP, et al.Guidelines for the prophylaxis and treatment of MRSA infections in the UK.

J Antimicrob Chemother 2006;57: 289-608


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Bronchopneumonia + CVD + ASHDBronchopneumonia + Acute MCI + Post CatethrerisationBronchopneumonia + CRF + Asthma + ASHDPost Surgery CVD + Hypertension + ASHDSBE, IV Drug abusers

Osteomyelitis + DM + ProstheseBlood Malignancy

TOTAL 33 CASES

Triggered causes of sepsis are figured below :

Experience in The Treatment of Sepsis due to

Gram-Positive Infections in a Private Hospital

January - December 2002

8

4

4

5

4

3

5


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LENGTH OF THERAPY

5 15 DAYS

MICROBIOLOGY LAB. PATHOGENIDENTIFICATION RESULTS

Staphylococcus spp 20 MRSA 8

Enterococcus spp 8 VRE 2

Streptococcus spp 5

REGIMEN OF THERAPY

SINGLE ANTIBIOTIC 15 Cases

(4 SBE cases with empirical Teicoplanin/Targocid,

others Vancomycin)

COMBINATION ANTIBIOTICS 18 Cases(CEPHALOSPORIN 5 cases, QUINOLONE 5 cases)


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ConclusionConclusion

1.1. IncreasedIncreased resistanceresistance pathogenspathogens inin communitycommunityandand hospitalhospital settingssettings..

2.2. IncreasedIncreased prevalenceprevalence ofof MRSAMRSA inin hospitalhospital

settingsetting andand implicatedimplicated inin morbiditymorbidity andandmortalitymortality..

3.3. Osteomyelitis,Osteomyelitis, softsoft tissuetissue infection,infection, nosocomialnosocomialbacteremia,bacteremia, andand endocarditisendocarditis areare seriousserious

infectionsinfections causedcaused byby mainlymainly GramGram--positivepositivebacteriabacteria..


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ConclusionConclusion

4.4. EmpiricalEmpirical treatmenttreatment forfor gramgram positivepositive couldcould bebestartedstarted whenwhen clinicalclinical impressionimpression supportssupports thethe

diagnosis,diagnosis, withwith oror withoutwithout laboratorylaboratory datadata..5.5. VancomycinVancomycin NewNew optionaloptional forfor treatmenttreatment

GramGram (+)(+) infectioninfection especiallyespecially forfor MRSAMRSA..

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New Optional for Treatmen Gram Positive Infection 1