updating antibiotic resistant trends in hap and vap in ap countries

Hospital Mortality and Inappropriate initial Antimicrobial Therapy Based on Classification of Infection Source Micek S T et al... Inappropriate definitive treatment 2.05 1.12-3.76 Inappr

P o - R e n H s u e h

National Taiwan University Hospital

Lancet Infect Dis 2008

Updating Antibiotic Resistant Trends

in HAP/VAP in AP Countries

Hospital Mortality and Inappropriate initial Antimicrobial Therapy

Based on Classification of Infection Source

Micek S T et al Antimicrob Agents Chemother 2010;54:1742-8.

Masterton RG et al J Antimicrob Chemother 2008;62:5-34.

Asian HAP Working Group Am J Infect Control 2008;36:S83-92.

Am J Respir Crit Care Med 2005;171:388–416.

HCAP , HAP

Guidelines

Key Elements Driving Development of Bacterial

Resistance and Risk of Treatment Failure

Wiest R, et al Gut 2012;61:297e310

Local epidemiology and resistance profiles

Severity

of patients

KPC NDM

Sputum from a ICU Patient

Predictors of Mortality for MDR GNB Infection

The study, The Patient, the Bug or the Drug?

Inappropriate definitive treatment 2.05 1.12-3.76

Inappropriate empirical treatment 1.37 1.25-1.51

Male gender 1.13 1.05-1.21

Beyond comorbidity and severity scores, inappropriate treatment and MDR were also identified as predictors of

mortality

Risk Factors for Multidrug-Resistant Pathogens (MDRP)

HAP, VAP, HCAP

or in the specific hospital unit

Hospitalization for 2 days or more in preceding 90 days

Residence in a nursing home or extended care fascility

Home infusion therapy (including antibiotics)

Chronic dialysis within 30 days

Bonten MJ et al Am J Respir Crit Care Med 2005;171:388-416.

De-escalation Therapy

therapy (>80% S or combination therapy)

 To improve outcomes: decrease mortality, prevent organ dysfunction, and decrease length of hospital stay

 To minimize resistance and improve

Initial Empiric Antibiotic Therapy for HAP, VAP, HCAP

Risk Factors for MDRP, Late Onset,

Any Disease Severity

Bonten MJ et al Am J Respir Crit Care Med 2005;171:388-416.

L pneumophila

+ a macrolide (azithromycin) or

a fluoroquinolone

(CIP, LVX)

Piperacilline/Tazobactam trong điều trị MDR

P.seudomonas

Một vấn đề quan trọng khi sử dụng

Piperacilline/tazobactam cho điều trị MDR Pseudo là phải xem xét đến là điểm gãy nhạy cảm của nó (≤64mcg/ml) theo như khuyến cáo bởi CLSI cao gấp 2 lần điểm gãy của Enterobactereacea (≤16mcg/ml)

Một NC cho thấy là BN nhiễm Pseudomonas aeruginosa

dùng Pip/Taz có tỷ lệ tử vong cao hơn khi MIC của

piperacillin 32-63 mcg/ml so với nhóm có MIC≤16mcg/ml

Do đó khi MIC của piperacillin từ 32-64 mcg/ml thì nên

cân nhắc dùng KS khác hơn là piperacillin/tazobactam.

Expert Rev Anti Infect Ther 8(1) 71-93 (2010)

Initial Empirical Antibiotic Treatment

for Late onset VAP- HAP in AsiaPotential pathogen Recommended antibiotic regimen

Antipseudomonal carbepenem (imipenem or meropenem)

or beta-lactam/beta-lactamase inhibitor

(piperacillin-tazobactam)

± Fluoroquinolone (ciprofloxacin or levofloxacin)

or aminoglycoside (amikacin, gentamicin, or tobramycin)

± linezolid or vancomycin cefoperazone/sulbactam + fluoroquinolones

or aminoglycosides + ampicillin/sulbactam (if sulbactam is not available)

± linezolid or vancomycin

or

fluoroquinolone (ciprofloxacin) plus aminoglycoside

± linezolid or vancomycin

Asian HAP Working Group Am J Infect Control 2008;36:S83-92.

Etiology of HAP in Asia

K pneumoniae P aeruginosa A baumannii MRSA

Chawla R Am J Infect Control 2008;36:S93-100.

Comparison of major Microorganisms Isolated

from HAP and VAP in Asian Countries (N=2454)

Chung DR, Hsueh PR, Song JH et al Am J Respir Crit Care Med 2011 (accepted)

HAP, VAP in Asia-Pacific

Chung DR, Hsueh PR, Song JH et al Am J Respir Crit Care Med 2011 15;184:1409-17

Carbapenems Non-susceptibility for

Major GNB Pathogens

COMPACT II study, Asia-Pacific, 2010

Kiratisin P et al Int J Antimicrob Agents 2012;39:311-6.

(90)

Healthcare-associated Respiratory Tract Infections

147 Pathogens, NTUH, 2012

16.3 3.4

19

12.5 11.6

Resistance in Major HAP Pathogens

Antimicrobial Resistance of Major Pathogens causing HAI NTUH, 2012

Carbapenem Nonsusceptibility among GNB Causing Healthcare-associated Infection

13 9.4

9.2

14.5

21 16.7

48.4

35.1

24.7 24.1

37.5 35.7

24.2 24.5

23.6 21.5

MRSA K pneumoniae

A baumannii

P aeruginosa

Susceptibility of Enterobacteriaceae

Cephalosporins

MIC (μg/ml) CLSI-2009 CLSI-2012 EUCAST

Bacteremia Caused by ESBL-Producing Enterobacteriaceae

Carbapenems versus Alternative Antibiotics for

Bacteraemia due to ESBL-Producing

Enterobacteriaceae

Systematic Review and Meta-analysis

VardakasKZ, et al J Antimicrob Chemother 2012; 67: 2793-803.

Definitive Treatment

Susceptible Breakpoints for Carbapenems

Antibiotic CLSI 2009,

M100-S19

CLSI 2010, M100-S20

CLSI

2011, M100-S21

CLSI 2012, M100-S22 (2013, M100-S23)

Treatment Outcome of 50 Patients with carbapenemase-producing Enterobacteriaceae

Carbapenem Monotherapy , 15 Studies

b P=0.02, odds ratio=7.5, and 95% confidence interval=1.32 to 42.52.

Tzouvelekis LS, et al Clin Microbiol Rev 2012;25:682-707.

Treatment Options for CRE/KPC

Combination Therapy is the Mainstream

 High-dose and prolonged-infusion carbapenem therapy as part of a combination regimen for CRE with carbapenem MICs ≤4 (or 8) mg/L

Plus gentamicin or colistin

 Double-carbapenem therapy = “doripenem + ertapenem”

Tzouvelekis LS, et al Clin Microbiol Rev 2012;25:682-707 Bulik CC, Nicolau DP Antimicrob Agents Chemother 2011;55:3002–4.

Antimicrobial Treatment of CPE

(Carbapenemase Producing Entobacteriaceae)

Summary of Recommendations

Hara GL, Hsueh PR et al J Chemother 2013.

Combination of a carbapenem with another active agent,

preferentially an aminoglycoside or colistin, could lower

mortality provided that the MIC of carbapenem for the

infecting organism is up to 4 mg/L - and probably up to 8 mg/L

- and the drug is administered in a

high-dose/prolonged-infusion regimen.

Susceptible Breakpoints for Carbapenems

P aeruginosa and Acinetobacter spp.

P aeruginosa

Antibiotic CLSI 2011,

M100-S21

CLSI 2013, M100-S23

CLSI 2012, Dose Doripenem - ≤2 0.5 g q8h Imipenem ≤4 ≤2 1g q8h Meropenem ≤4 ≤2 1g q8h

Lee NY, Ko WC, et al Pharmacotherapy 2007;27:1506-11.

Carbapenem and Sulbactam against Imipenem-resistant A baumannii

In Vitro Synergy Studies, 4 Patients

Facing the Gram-Negative MDRO

Optimizing Antibiotic Empiricism

AB, A baumannii; HI, H influenzae; MC, M catarrhalis;

PA, P aeruginosa; SP, S pneumoniae;

Ciprofloxacin

Extended coverage

Synergy resistance

Management Recommendations on Nosocomial Pneumonia caused

by XDR or PDR A baumannii

Jean SS, Hsueh PR Expert Opin Pharmacother 2011;12:2145-8.

 Tigecycline plus imipenem,

or colistin

 Tigecycline plus imipenemand amikacin

Colistin dosing? higher loading doses

A loading dose of 300 to 400 mg CBA (9 MU) followed by a maintenance dose of 150 mg (4.5 MU) twice (CID 2013;56:398-404 )

Colistin (1 vial of colistimethate for injection contains 150 mg CBA)

Internationally, 150 mg CBA is equivalent to 4.5 million international units (IU)