Journal
CLINICAL INFECTIOUS DISEASES
Volume 73, Issue 11, Pages E3842-E3850Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/ciaa1479
Keywords
piperacillin-tazobactam; meropenem; extended spectrum beta-lactamase; bloodstream infection
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Funding
- Study Education and Research Committee of Pathology Queensland
- Australian Infectious Disease Centre
- Australian Genome Research Facility
- Royal College of Pathologists of Australasia Foundation
- Merck Sharp Dohme
- National Health and Medical Research Council [GNT1157530]
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This study showed that in the MERINO trial, the best MIC value for predicting 30-day mortality in patients treated with piperacillin/tazobactam was identified. Excluding nonsusceptible strains, the absolute risk increase for 30-day mortality was smaller for piperacillin/tazobactam compared to meropenem, while strains coharboring ESBL and OXA genes had the highest risk of mortality increase.
Introduction. This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. Methods. Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. Results. In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval [CI] 2.8-87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%-15%) and 8% (95% CI 2%-15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI -1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum beta-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%-28%). Conclusions. After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.
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