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Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended-spectrum β-lactamase bacteremia.
Clin Infect Dis 2015; 60(9):1319-25CI

Abstract

BACKGROUND

The effectiveness of piperacillin-tazobactam (PTZ) for the treatment of extended-spectrum β-lactamase (ESBL) bacteremia is controversial. We compared 14-day mortality of PTZ vs carbapenems as empiric therapy in a cohort of patients with ESBL bacteremia who all received definitive therapy with a carbapenem.

METHODS

Patients hospitalized between January 2007 and April 2014 with monomicrobial ESBL bacteremia were included. A decrease of >3 doubling dilutions in the minimum inhibitory concentration for third-generation cephalosporins tested in combination with 4 µg/mL of clavulanic acid was used to confirm ESBL status. The primary exposure was empiric therapy, defined as antibiotic therapy administered to a patient before ESBL status was known. Patients were excluded if they did not receive a carbapenem after ESBL production was identified. The primary outcome was time to death from the first day of bacteremia. Propensity scores using inverse probability of exposure weighting (IPW) were used to estimate the probability that a patient would receive PTZ vs carbapenems empirically. We calculated overall hazard ratios for mortality censored at 14 days using Cox proportional hazards models on an IPW-adjusted cohort.

RESULTS

A total of 331 unique patients with ESBL bacteremia were identified. One hundred three (48%) patients received PTZ empirically and 110 (52%) received carbapenems empirically. The adjusted risk of death was 1.92 times higher for patients receiving empiric PTZ compared with empiric carbapenem therapy (95% confidence interval, 1.07-3.45).

CONCLUSIONS

PTZ appears inferior to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of invasive ESBL infections, early carbapenem therapy should be considered. Our findings should not be extended to β-lactam/β-lactamase inhibitor combinations in development, as limited clinical data are available for these agents.

Authors+Show Affiliations

Department of Pediatrics, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland.Department of Medicine, Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia.Department of Epidemiology and Public Health, University of Maryland School of Medicine.Department of Epidemiology and Public Health, University of Maryland School of Medicine.Department of Medicine, Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia.Department of Pharmacy, Johns Hopkins Hospital.Department of Pharmacy, Johns Hopkins Hospital.Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25586681

Citation

Tamma, Pranita D., et al. "Carbapenem Therapy Is Associated With Improved Survival Compared With Piperacillin-tazobactam for Patients With Extended-spectrum Β-lactamase Bacteremia." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 60, no. 9, 2015, pp. 1319-25.
Tamma PD, Han JH, Rock C, et al. Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended-spectrum β-lactamase bacteremia. Clin Infect Dis. 2015;60(9):1319-25.
Tamma, P. D., Han, J. H., Rock, C., Harris, A. D., Lautenbach, E., Hsu, A. J., ... Cosgrove, S. E. (2015). Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended-spectrum β-lactamase bacteremia. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 60(9), pp. 1319-25. doi:10.1093/cid/civ003.
Tamma PD, et al. Carbapenem Therapy Is Associated With Improved Survival Compared With Piperacillin-tazobactam for Patients With Extended-spectrum Β-lactamase Bacteremia. Clin Infect Dis. 2015 May 1;60(9):1319-25. PubMed PMID: 25586681.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended-spectrum β-lactamase bacteremia. AU - Tamma,Pranita D, AU - Han,Jennifer H, AU - Rock,Clare, AU - Harris,Anthony D, AU - Lautenbach,Ebbing, AU - Hsu,Alice J, AU - Avdic,Edina, AU - Cosgrove,Sara E, AU - ,, Y1 - 2015/01/13/ PY - 2014/06/23/received PY - 2014/10/13/accepted PY - 2015/1/15/entrez PY - 2015/1/15/pubmed PY - 2016/1/26/medline KW - ESBL KW - carbapenem KW - gram-negative KW - piperacillin-tazobactam KW - resistance SP - 1319 EP - 25 JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin. Infect. Dis. VL - 60 IS - 9 N2 - BACKGROUND: The effectiveness of piperacillin-tazobactam (PTZ) for the treatment of extended-spectrum β-lactamase (ESBL) bacteremia is controversial. We compared 14-day mortality of PTZ vs carbapenems as empiric therapy in a cohort of patients with ESBL bacteremia who all received definitive therapy with a carbapenem. METHODS: Patients hospitalized between January 2007 and April 2014 with monomicrobial ESBL bacteremia were included. A decrease of >3 doubling dilutions in the minimum inhibitory concentration for third-generation cephalosporins tested in combination with 4 µg/mL of clavulanic acid was used to confirm ESBL status. The primary exposure was empiric therapy, defined as antibiotic therapy administered to a patient before ESBL status was known. Patients were excluded if they did not receive a carbapenem after ESBL production was identified. The primary outcome was time to death from the first day of bacteremia. Propensity scores using inverse probability of exposure weighting (IPW) were used to estimate the probability that a patient would receive PTZ vs carbapenems empirically. We calculated overall hazard ratios for mortality censored at 14 days using Cox proportional hazards models on an IPW-adjusted cohort. RESULTS: A total of 331 unique patients with ESBL bacteremia were identified. One hundred three (48%) patients received PTZ empirically and 110 (52%) received carbapenems empirically. The adjusted risk of death was 1.92 times higher for patients receiving empiric PTZ compared with empiric carbapenem therapy (95% confidence interval, 1.07-3.45). CONCLUSIONS: PTZ appears inferior to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of invasive ESBL infections, early carbapenem therapy should be considered. Our findings should not be extended to β-lactam/β-lactamase inhibitor combinations in development, as limited clinical data are available for these agents. SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/25586681/Carbapenem_therapy_is_associated_with_improved_survival_compared_with_piperacillin_tazobactam_for_patients_with_extended_spectrum_β_lactamase_bacteremia_ L2 - https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/civ003 DB - PRIME DP - Unbound Medicine ER -