updating antibiotic resistant trends in hap and vap in ap countries

Po-Ren Hsueh National Taiwan University Hospital Lancet Infect Dis 2008 Updating Antibiotic Resistant Trends in HAP/VAP in AP Countries HAP (Ward) VAP (ICU) HCAP (Nursing Home) Hospital-acquired Pneumonia 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 CR-, MDR-, XDR-, PDR-PA CR-, MDR-, XDR-, PDR-AB Main MDRO in Hospitals Sputum from a ICU Patient Predictors of Mortality for MDR GNB Infection The study, The Patient, the Bug or the Drug? Meta-analysis  Acinetobacter spp, P. aeruginosa, and Enterobacteriaceae  Independent predictors Vardakas KZ et al. J Infect 2013;66:401-14. Risk ratio 95% CI Cancer 1.65 1.13-2.39 Prior or current ICU stay 1.27 1.02-1.56 Septic shock 3.36 2.47-4.57 ICU stay 2.15 1.45-3.20 Pneumonia 1.6 1.09-2.52 Isolation of MDRGN bacteria 1.49 1.21-1.83 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  Antimicrobial therapy in preceding 90 days  Current hospitalization of 5 days or more  High frequency of antibiotic resistance in the community or in the specific hospital unit  Presence of risk factor for HCAP  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  Home wound care  Family member with MDRP  Immunosuppressive disease and/or therapy Bonten MJ et al. Am J Respir Crit Care Med 2005;171:388-416. De-escalation Therapy Administer the broadest-spectrum antibiotic 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 cost- effectiveness De-escalation: Culture result, fever, short duration P. aeruginosa, non-fermenters Rello J. Crit Care Med 2004;32:2183-90. [...]... beta-lactam/beta-lactamase inhibitor (piperacillinP aeruginosa tazobactam) Acinetobacter ESBL (+) K pneumoniae ± Fluoroquinolone (ciprofloxacin or levofloxacin) MRSA 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)... 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) Incidence of CR-, MDR-, XDR-, PDRP aeruginosa and Acinetobacter spp HAP, VAP in Asia-Pacific P aeruginosa % 100 90 80 70 60 50 40 30 20 10 0 Acinetorbactr spp 82 67.3 51.1 42.8 30.1 4.9 CR MDR XDR 0.7 0.2 PDR Chung... for CRE with carbapenem MICs ≤4 (or 8) mg/L  Carbapenem-based combinations  Plus colistin, tigecycline, or an aminoglycoside  Colistin-based combinations  Plus a carbapenem, tigecycline, or an aminoglycoside  Tigecycline-based combinations  Plus gentamicin or colistin  Double-carbapenem therapy = “doripenem + ertapenem” Tzouvelekis LS, et al Clin Microbiol Rev 2012;25:682-707 Bulik CC, Nicolau... 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...Initial Empiric Antibiotic Therapy for HAP, VAP, HCAP Risk Factors for MDRP, Late Onset, Any Disease Severity Potential pathogen Combination antibiotic therapy Pathogens (early-onset) + Cefepime, ceftazidime MDRP or P aeruginosa Imipenem or meropenem K pneumoniae (ESBL) or Acinetobacter spp Piperacillin-tazobactam L pneum ophila + a macrolide (azithromycin) or a fluoroquinolone (CIP,... 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 50 42.1 40 28.2 30 26.3 23 20 18 14 23 21 20 17.6 16 16 11 10 23 11.8 18 17.8 13.1 9 9 5.8 7.7 7.6 0 China Korea Malaysia Philippines Taiwan Thailand Chawla R Am J Infect Control 2008;36:S93-100 Comparison... Antimicrobial Treatment of CPE (Carbapenemase Producing Entobacteriaceae) Summary of Recommendations 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/prolongedinfusion regimen Hara GL,... Pharmacotherapy 2007;27:1506-11 Facing the Gram-Negative MDRO Optimizing Antibiotic Empiricism Colistin Enterobacteriaceae (CS: ESBL, AmpC, MDR…) Fosfomycin Amikacin Anaerobes Imipenem CRPA + HI, MC Ciprofloxacin AB, A baumannii; HI, H influenzae; MC, M catarrhalis; PA, P aeruginosa; SP, S pneumoniae; CR, carbapenem-susceptible; CR, carbapenem -resistant Synergy resistance Sulbactam Cefoperazoneor ampicillin-)... 2013 Susceptible Breakpoints for Carbapenems P aeruginosa and Acinetobacter spp P aeruginosa 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 Antibiotic A baumannii Antibiotic CLSI 2013, M100-S23 Doripenem - Imipenem ≤4 Meropenem ≤4 Carbapenem and Sulbactam against Imipenem -resistant A baumannii In Vitro Synergy Studies,... 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 Asia Potential pathogen Recommended antibiotic regimen . Hospital Lancet Infect Dis 2008 Updating Antibiotic Resistant Trends in HAP/ VAP in AP Countries HAP (Ward) VAP (ICU) HCAP (Nursing Home) Hospital-acquired Pneumonia Hospital Mortality and Inappropriate. (ciprofloxacin or levofloxacin) or aminoglycoside (amikacin, gentamicin, or tobramycin) ± linezolid or vancomycin cefoperazone/sulbactam + fluoroquinolones or aminoglycosides + ampicillin/sulbactam. 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. 14 11 9 18 21 17.8 16 9 23 20 28.2 16 23 18 7.6 5.8 7.7 26.3 42.1 23 17.6 13.1 11.8 0 10 20 30 40 50 China