The influence of metallo-β-lactamase production on mortality in nosocomial Pseudomonas aeruginosa infections

OBJECTIVES: To assess the effect of metallo-beta-lactamase (MBL) production on Pseudomonas aeruginosa nosocomial infection mortality and to identify the determinants of such effect. METHODS: A cohort study of patients with P. aeruginosa nosocomial infections was conducted at two teaching hospitals. MBL was detected by ceftazidime/2-mercaptopropionic disc approximation test and selected isolates were submitted to PCR using bla(SPM-1) primer. Molecular typing was performed by DNA macrorestriction. To evaluate the influence of MBL on mortality a Cox proportional hazards model was performed using a hierarchized framework of the variables. RESULTS: A total of 298 patients with P. aeruginosa infections were included. Infections by MBL-carrying Pseudomonas aeruginosa (MBL-PA) resulted in higher in-hospital mortality than those by non-MBL-PA (51.2% versus 32.1%, respectively; relative risk 1.60, 95% CI 1.20-2.12) and higher mortality rates [17.3 per 1000 versus 11.8 per 1000 patient-days, respectively; hazard ratio (HR) 1.55, 95% CI 1.06-2.27]. In the final multivariate model, severe sepsis or septic shock [adjusted HR (AHR) 3.62, 95% CI 2.41-5.43], age (AHR 1.02, 95% CI 1.01-1.03) and use of appropriate therapy<or=72 h (AHR 0.49, 95% CI 0.32-0.76) were significantly associated with mortality. Fourteen MBL-PA tested carried the blaSPM-1 gene. Clonal dissemination was documented in both hospitals. CONCLUSIONS: MBL-PA infections resulted in higher mortality rates most likely related to the severity of these infections and less frequent early institution of appropriate antimicrobial therapy. Empirical treatments should be reviewed at institutions with high prevalence of MBL.

[1]  A. Peleg,et al.  Dissemination of the metallo-beta-lactamase gene blaIMP-4 among gram-negative pathogens in a clinical setting in Australia. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[2]  A. Zavascki,et al.  Outbreak of carbapenem-resistant Pseudomonas aeruginosa producing SPM-1 metallo-{beta}-lactamase in a teaching hospital in southern Brazil. , 2005, The Journal of antimicrobial chemotherapy.

[3]  G. Rossolini,et al.  Novel Acquired Metallo-β-Lactamase Gene, blaSIM-1, in a Class 1 Integron from Acinetobacter baumannii Clinical Isolates from Korea , 2005, Antimicrobial Agents and Chemotherapy.

[4]  D. Church,et al.  Population-based epidemiological study of infections caused by carbapenem-resistant Pseudomonas aeruginosa in the Calgary Health Region: importance of metallo-beta-lactamase (MBL)-producing strains. , 2005, The Journal of infectious diseases.

[5]  Timothy R. Walsh,et al.  Metallo-β-Lactamases: the Quiet before the Storm? , 2005, Clinical Microbiology Reviews.

[6]  M. Kaufmann,et al.  Outbreak of Carbapenem-Resistant Pseudomonas aeruginosa Producing VIM-8, a Novel Metallo-β-Lactamase, in a Tertiary Care Center in Cali, Colombia , 2004, Journal of Clinical Microbiology.

[7]  Yasuaki Yamada,et al.  Clinical and bacteriological characteristics of IMP-type metallo-beta-lactamase-producing Pseudomonas aeruginosa. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[8]  D. Livermore,et al.  Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare? , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  H. Giamarellou Prescribing guidelines for severe Pseudomonas infections. , 2002, The Journal of antimicrobial chemotherapy.

[10]  Richard A. Moore,et al.  Nosocomial Outbreak of Carbapenem-Resistant Pseudomonas aeruginosa with a New blaIMP Allele, blaIMP-7 , 2002, Antimicrobial Agents and Chemotherapy.

[11]  Ronald N. Jones,et al.  Contemporary Assessment of Antimicrobial Susceptibility Testing Methods for Polymyxin B and Colistin: Review of Available Interpretative Criteria and Quality Control Guidelines , 2001, Journal of Clinical Microbiology.

[12]  Y. Arakawa,et al.  Convenient Test for Screening Metallo-β-Lactamase-Producing Gram-Negative Bacteria by Using Thiol Compounds , 2000, Journal of Clinical Microbiology.

[13]  S. Huttly,et al.  The role of conceptual frameworks in epidemiological analysis: a hierarchical approach. , 1997, International journal of epidemiology.

[14]  D H Persing,et al.  Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing , 1995, Journal of clinical microbiology.

[15]  J. Concato,et al.  The Risk of Determining Risk with Multivariable Models , 1993, Annals of Internal Medicine.

[16]  W. Knaus,et al.  Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. , 1992, Chest.

[17]  B. Yangco,et al.  CDC definitions for nosocomial infections. , 1989, American journal of infection control.

[18]  E. Bruck,et al.  National Committee for Clinical Laboratory Standards. , 1980, Pediatrics.

[19]  M. Kaufmann,et al.  Pulsed-field gel electrophoresis. , 1998, Methods in molecular medicine.

[20]  C. Mackenzie,et al.  A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. , 1987, Journal of chronic diseases.