Update on Resistance and Epidemiology of Nosocomial Respiratory Pathogens in Asia. Po-Ren Hsueh. National Taiwan University Hospital

Transcription

1 Update on Resistance and Epidemiology of Nosocomial Respiratory Pathogens in Asia Po-Ren Hsueh National Taiwan University Hospital

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3 Ventilator-associated Pneumonia

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5 Microbiological Report Sputum from a ICU Patient

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7 Asian HAP Working Group. Am J Infect Control 2008;36:S Masterton RG et al. J Antimicrob Chemother 2008;62:5-34.

8 Selection of Antimicrobials in the Management of HAP (UK) Empirical antibiotic therapy of patients in an individual unit should be based on Knowledge of the nature and susceptibility patterns of the pathogens Duration of hospital stay (i.e. early- or late-onset infection) Recent administration of antibiotic therapy and co-morbidities Definitive therapy should be determined by culture and susceptibility test results Masterton RG et al. J Antimicrob Chemother 2008;62:5-34.

9 Etiology of HAP in Asia K. pneumoniae P. aeruginosa A. baumannii MRSA China Korea Malaysia Philippines Taiwan Thailand Chawla R. Am J Infect Control 2008;36:S

10 Susceptibility to P. aeruginosa and A. baumannii SENTRY, , Asia-Pacific Region % P. aeruginosa (n=898) A. baumannii (n=411) Ceftazidime Cefepime Pip/Taz Ciprofloxacin Amikacin Imipenem Gales AC et al. Clin Microbiol Infect 2006; 12:

11 Percentage of Isolates Susceptibility of Pseudomonas species TEST, Asia/Pacific Rim, (n=1370) 100 a AN CPE CAZ CRO IPM MEM LVX TZP

12 Percentage of Isolates Susceptibility of Acinetobacter species TEST, Asia/Pacific Rim, (n=985) a AN CPE CAZ CRO IPM MEM LVX MNO TZP

13 Healthcare-associated Respiratory Infections in ICUs Taiwan Nosocomial Infection Surveillance Systems, TNIS, Medical centers (n=901) Regional hospitals (n=1,571) % P. aeruginosa A. baumannii S. aureus K. pneumoniae E. coli E. cloacae S. maltophilia

14 Major Resistant Pathogens in ICUs Taiwan Nosocomial Infection Surveillance Systems, TNIS, Medical centers Regional hospitals % MRSA CRKP CRAB CRPA Lee CM, et al. Infect Control J 2010.

15 Healthcare-associated Respiratory Tract Infections 365 Pathogens, NTUH, 2009 Klebsiella spp P. aeruginosa S. aureus Acinetobacter spp MRSA, 51.9% S. maltophilia E. coli Enterobacter %

16 % 70 Resistance in Major HAP Pathogens NTUH, 2009 K. pneumoniae P. aeruginosa A. baumannii Ceftazidime Cefepime Pip/Taz Ciprofloxacin Imipenem Amikacin (ertapenem)

17 Antibiotic Treatment of Infections due to MDR or XDR Superbugs P. aeruginosa Combination with two susceptible agents Colistin alone or in combination (XDR) Fosfomycin in combination A. baumannii A carbapenem plus sulbactam Colistin alone or in combination Tigecycline alone or in combination Bonten MJ et al. Am J Respir Crit Care Med 2005;171:

18 Susceptibility to A. baumannii SMART, 2005, 10 ICUs (N=167), Taiwan; SENTRY (AP) Intermediate, 82.5% AMP/SUL CFP/SUL Fosfomycin Colistin Tigecycline Polymyxin B Jean SS, Hsueh PR et al. Int J Antimicrob Agents 2009;33: Gales AC et al. Clin Microbiol Infect 2006; 12:

19 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:

20 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 PLUS Ciprofloxacin or levofloxacin or Amikacin, gentamicin, or tobramicin L. pneumophila + a macrolide (azithromycin) or a fluoroquinolone (CIP, LVX) MRSA PLUS Linezolid or vancomycin Bonten MJ et al. Am J Respir Crit Care Med 2005;171:

21 Validation of the ATS/IDSA Guidelines for HAP in the ICU 276 patients Group 1 (early onset without risk factors for MDRO, n=38) Group 2 (late onset or risk factors for MDRO, n=238) Adherence to guidelines Group 2: more guideline adherence, more adequate treatment and a trend to a better clinical response in Did not influence mortality Ferrer M et al. Clin Infect Dis 2010;50:

22 Initial Empirical Antibiotic Treatment for Late onset VAP- HAP in Asia Potential pathogen MDR pathogens P. aeruginosa Acinetobacter ESBL (+) K. pneumoniae MRSA Recommended antibiotic regimen Antipseudomonal carbepenem (imipenem or meropenem) or beta-lactam/beta-lactamase inhibitor (piperacillintazobactam) 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 an aminoglycoside linezolid or vancomycin Asian HAP Working Group. Am J Infect Control 2008;36:S83-92.

23 Antibiotic Regimens against Specific Antibiotic-resistant Pathogens- HAP in Asia Pathogen Rank Antibiotic regimen MRSA 1 Vancomycin or teicoplanin 2 Linezolid or tigecycline MDR P. aeruginosa 1 Piperacillin/tazobactam or carbapenems aminoglycosides or fluoroquinolones (ciprofloxacin) 2 Polymyxin B or colistin ciprofloxacin MDR Acinetobacter 1 Cefoperazone/sulbactam and/or tigecycline ESBL (+) K. pneumoniae or E. coli 2 Polymyxin B or colistin 1 Carbapenems or tigecycline 2 Piperacillin/tazobactam Asian HAP Working Group. Am J Infect Control 2008;36:S83-92.

24 Fluoroquinolones in HAP and VAP Advantages High concentrations in lung tissue and respiratory secretions Synergistic activity in combined treatment against P. aeruginosa Substitution for aminoglycosides Impaired renal function or at risk for renal dysfunction Need to extend antibiotic coverage to intracellular pathogens No need to monitor plasma drug concentration to ensure effectiveness and to avoid toxicity Possibility of sequential therapy in patients with satisfactory clinical response Synergistic interaction with antifungals (improve outcomes) Patients with suspected or confirmed allergy to -lactams Lower capacity to induce P. aeruginosa resistance Lvarez-Lerma F et al. Clin Microbiol Infect Dis 2006;12 (Suppl 3): Stergiopoulou T et al. J Antimicrob Chemother 2009;63:343-8.

25 % Emergence of Resistance among P. aeruginosa The emergence of resistance occurred less often with quinolones than with imipenem Imipenem Ciprofloxacin Cirpofloxacin Levofloxacin Fink et al Torres et al West et al Shorr AF et al. Clin Infect Dis 2005;40:S

26 % Treatment of Severe HAP Ciprofloxacin vs. Imipenem Success rate P. aeruginosa Success P. aeruginosa Resistance (PA) Clinical success Ciprofloxacin ( g/d) (n=41) Imipenem 2-4 g/d (n=34) 25 Microbiological success /14 4/12 Torres A et al. Thorax 2000;55:

27 Ciprofloxacin and Levofloxacin Equal in P. aeruginosa??? Resistance Selection

28 Nonsusceptibility to Fluoroquinolone in P. aeruginosa Nosocomial Infections, NTUH, 2009 SMART, ICUs, 2005 % Ciprofloxacin Levofloxacin % Ciprofloxacin Levofloxacin Resistant Resistant Jean SS, Hsueh PR et al. Int J Antimicrob Agents 2008

29 Ciprofloxacin and Levofloxacin Not Equal in P. aeruginosa Antimicrobial (steady state) MIC 50 (μg/ml) 1 C max (μg/ml) AUC 0-24 (μg.h/ml) C max /MIC AUC 0-24 / MIC Ciprofloxacin (IV 400 mg q8h) Levofloxacin (IV 750 mg q24) Free drug, 70% for both AUC/MIC >157:1, the threshold to suppress emergence of resistance Jean SS, Hsueh PR et al. Int J Antimicrob Agents 2008 Jumbe N et al. J Clin Invest 2003;112:

30 Clin Infect Dis 2004; 39: Kaye KS et al. Antimicrob Agents Chemother 2006; 50:

31 Trend of Hospital Fluoroquinolone Use 1999 (n=24), (n=35), USA p=0.01 p= p >0.05 Clinical Infectious Diseases 2004; 39: Polk RE et al. Clin Infect Dis 2004; 39:

32 Individual Hospital Levofloxacin Use and FQ Resistance in P. aeruginosa 2000, USA N=27, p= Clinical Infectious Diseases 2004; 39: Polk RE et al. Clin Infect Dis 2004; 39:

33 Risk Factors for FQ-Resistant P. aeruginosa Multivariate Analysis Variable Adjusted OR (95% CI) for: FQ-resistant FQ-susceptible (n=147) (n=255) Levofloxacin 1.7 ( ) 0.6 ( ) Ciprofloxacin 1.2 ( ) 1.0 ( ) Other antibiotics 2.2 ( ) 2.1 ( ) ICU stay 3.3 ( ) 3.7 ( ) Presence of 2 comorbid conditions 1.7 ( ) 1.6 ( ) TAR of >6 days 1.8 ( ) Age of 64 yrs 1.4 ( ) Kaye KS et al. Antimicrob Agents Chemother 2006; 50:

34 Lee YJ, Hsueh PR et al. Int J Antimicrob Agents 2010;35:261-4.

35 Ciprofloxacin-resistant P. aeruginosa Ciprofloxacin and Levofloxacin Usages Lee YJ, Hsueh PR et al. Int J Antimicrob Agents 2010;35:261-4.

36 Ciprofloxacin-resistant P. aeruginosa Parenteral Ciprofloxacin and Levofloxacin Usages Lee YJ, Hsueh PR et al. Int J Antimicrob Agents 2010;35:261-4.

37 Ciprofloxacin-resistant P. aeruginosa IV+PO Ciprofloxacin and Levofloxacin Usages Lee YJ, Hsueh PR et al. Int J Antimicrob Agents 2010;35:261-4.

38 Reasons for the Differences Better activity of ciprofloxacin Fluoroquinolone-resistant P. aeruginosa are most likely to originate in the gastrointestinal tract Higher bioavailability of levofloxacin (100%) than ciprofloxacin (60% 70%) Higher GI concentrations of ciprofloxacin may eliminate more borderline fluoroquinolones-susceptible organisms and levofloxacin may select more fluoroquinolone-resistant strains In vitro serial passage studies Rate of accumulation of P. aeruginosa mutants with a drug MIC of 4 g/ml was fastest for levofloxacin and slowest for ciprofloxacin Polk RE et al. Clin Infect Dis 2004; 39: Gilbert DN et al. Antimicrob Agents Chemother 2001;45:

39 Dynamic Selection of Quinolone Resistance Rate for Emergence of Resistance Phenotypes K. pneumoniae, E. cloacae, S. marcescens Trovafloxacin > levofloxacin > ciprofloxacin P. aeruginosa Levofloxacin > trovafloxacin > ciprofloxacin In vitro behavior can predict clinical resistance??? Gilbert DN et al. Antimicrob Agents Chemother 2001;45:

40 Risks for Acquisition of FQ-Resistant P. aeruginosa Ciprofloxacin and Levofloxacin Individual patient Exposure to levofloxacin, but not to ciprofloxacin, was associated with increased risk For hospitals Different FQs prescribing should be examined Hospital s formulary: which FQ should be included? Ciprofloxacin is more appropriate than levofloxacin for empirical therapy for suspected pseudomonal infections Kaye KS et al. Antimicrob Agents Chemother 2006; 50:

41 Fluoroquinolone Use Different Resistance Selection for P. aeruginosa? Need adequate dosage Ciprofloxacin: 400 mg q8h Levofloxacin: 750 mg qd Combination therapy vs. monotherapy Clonal spreads? Appropriate Use

42 Ciprofloxacin nonsusceptibility (%) DDD/1000 patient-days Fluoroquinolone Consumption and Ciprofloxacin Nonsusceptibility NTUH, Lai CC, Hsueh PR et al. Data submitted

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