Efficacy of Appropriate Antimicrobial Therapy on the Survival of Patients With Carbapenem Nonsusceptible Klebsiella Pneumoniae Infection

AbstractThe impact of antimicrobial treatment on the outcome of carbapenem nonsusceptible Klebsiella pneumoniae (CnsKP) infections needs to be elucidated. This nationwide, multicenter study was conducted to evaluate the impact of appropriate antimicrobial therapy on 14-day mortality among patients with CnsKP infection in Taiwan.Patients with CnsKP infections from 11 medical centers and 4 regional hospitals in Taiwan were enrolled in 2013. Carbapenem nonsusceptibility was defined as a minimum inhibitory concentration of ≥2 mg/L for imipenem or meropenem. Predictors of 14-day mortality were determined using the Cox proportional regression model. The influence of infection severity on the impact of appropriate use of antimicrobials on 14-day mortality was determined using the Acute Physiology and Chronic Health Evaluation (APACHE) II score.Overall 14-day mortality was 31.8% (49/154). Unadjusted mortality for appropriate antimicrobial therapy was 23.1% (18/78 patients). Appropriate therapy was independently associated with reduced mortality (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.24–0.80; P = 0.007). A subgroup analysis revealed that the benefit of appropriate therapy was limited to patients with higher APACHE II scores (HR for patients with scores >15 and ⩽35, 0.46; 95% CI 0.23–0.92; and for those with scores >35, 0.14; 95% CI, 0.02–0.99).In conclusion, appropriate antimicrobial therapy significantly reduces 14-day mortality for CnsKP infections. Survival benefit is more notable among more severely ill patients.

[1]  M. Bassetti,et al.  Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study. , 2015, The Journal of antimicrobial chemotherapy.

[2]  M. Falagas,et al.  Characteristics, risk factors and outcomes of carbapenem-resistant Klebsiella pneumoniae infections in the intensive care unit. , 2015, The Journal of infection.

[3]  S. Bauer,et al.  Impact of Combination Antimicrobial Therapy on Mortality Risk for Critically Ill Patients with Carbapenem-Resistant Bacteremia , 2015, Antimicrobial Agents and Chemotherapy.

[4]  E. Abdala,et al.  Treatment of KPC-producing Enterobacteriaceae: suboptimal efficacy of polymyxins. , 2015, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[5]  L. Leibovici,et al.  Combination therapy for carbapenem-resistant Gram-negative bacteria. , 2014, The Journal of antimicrobial chemotherapy.

[6]  G. Daikos,et al.  Treating infections caused by carbapenemase-producing Enterobacteriaceae. , 2014, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[7]  S. Conlan,et al.  Surveillance of Carbapenem-Resistant Klebsiella pneumoniae: Tracking Molecular Epidemiology and Outcomes through a Regional Network , 2014, Antimicrobial Agents and Chemotherapy.

[8]  V. Miriagou,et al.  Carbapenemase-Producing Klebsiella pneumoniae Bloodstream Infections: Lowering Mortality by Antibiotic Combination Schemes and the Role of Carbapenems , 2014, Antimicrobial Agents and Chemotherapy.

[9]  Yu-Jiun Chan,et al.  Clinical and microbiological characteristics of tigecycline non-susceptible Klebsiella pneumoniae bacteremia in Taiwan , 2014, BMC Infectious Diseases.

[10]  Y. Chuang,et al.  National Surveillance Study on Carbapenem Non-Susceptible Klebsiella pneumoniae in Taiwan: The Emergence and Rapid Dissemination of KPC-2 Carbapenemase , 2013, PloS one.

[11]  R. Bonomo,et al.  “Stormy waters ahead”: global emergence of carbapenemases , 2013, Front. Microbiol..

[12]  R. Bonomo,et al.  Carbapenem-resistant Enterobacteriaceae: a review of treatment and outcomes. , 2013, Diagnostic microbiology and infectious disease.

[13]  N. Petrosillo,et al.  Treatment of carbapenem-resistant Klebsiella pneumoniae: the state of the art , 2013, Expert review of anti-infective therapy.

[14]  G. Daikos,et al.  Bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae: a clinical perspective , 2012, Expert review of anti-infective therapy.

[15]  G. Daikos,et al.  Carbapenemases in Klebsiella pneumoniae and Other Enterobacteriaceae: an Evolving Crisis of Global Dimensions , 2012, Clinical Microbiology Reviews.

[16]  M. Bassetti,et al.  Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  Yi-Tsung Lin,et al.  Impact of appropriate antimicrobial therapy on mortality associated with Acinetobacter baumannii bacteremia: relation to severity of infection. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[18]  P. Nordmann,et al.  Carbapenem resistance in Enterobacteriaceae: here is the storm! , 2012, Trends in molecular medicine.

[19]  Yi-Tsung Lin,et al.  Characteristics of healthcare-associated and community-acquired Klebsiella pneumoniae bacteremia in Taiwan. , 2012, The Journal of infection.

[20]  D. Paterson,et al.  Treatment Outcome of Bacteremia Due to KPC-Producing Klebsiella pneumoniae: Superiority of Combination Antimicrobial Regimens , 2012, Antimicrobial Agents and Chemotherapy.

[21]  S. Pournaras,et al.  Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment. , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[22]  K. Laupland,et al.  Incidence, risk factors, and outcomes of Klebsiella pneumoniae bacteremia. , 2009, The American journal of medicine.

[23]  D. Nicolau,et al.  In Vivo Pharmacodynamic Profile of Tigecycline against Phenotypically Diverse Escherichia coli and Klebsiella pneumoniae Isolates , 2009, Antimicrobial Agents and Chemotherapy.

[24]  C. Bamia,et al.  Prospective Observational Study of the Impact of VIM-1 Metallo-β-Lactamase on the Outcome of Patients with Klebsiella pneumoniae Bloodstream Infections , 2009, Antimicrobial Agents and Chemotherapy.

[25]  R. Podschun,et al.  Klebsiella spp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors , 1998, Clinical Microbiology Reviews.

[26]  D. Pittet,et al.  Does antibiotic selection impact patient outcome? , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[27]  M. Ferraro Performance standards for antimicrobial susceptibility testing , 2001 .