Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study

Henderson, A, Paterson, DL, Chatfield, MD, Tambyah, PA, Lye, DC, De, PP, Lin, RTP, Chew, KL, Yin, M, Lee, TH, Yilmaz, M, Cakmak, R, Alenazi, TH, Arabi, YM, Falcone, M, Bassetti, M, Righi, E, Rogers, BA, Kanj, SS, Bhally, H, Iredell, J, Mendelson, M, Boyles, TH, Looke, DFM, Runnegar, NJ, Miyakis, S, Walls, G, Khamis, MAI, Zikri, A, Crowe, A, Ingram, PR, Daneman, N, Griffin, P, Athan, Eugene, Roberts, L, Beatson, SA, Peleg, AY, Cottrell, K, Bauer, MJ, Tan, E, Chaw, K, Nimmo, GR, Harris-Brown, T, Harris, PNA, MERINO Trial Investigators and Australasian Society for Infectious Disease Clinical Research Network (ASID-CDN) 2020, Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study, Clinical Infectious Diseases, pp. 1-9, doi: 10.1093/cid/ciaa1479.

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Title Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study
Author(s) Henderson, A
Paterson, DL
Chatfield, MD
Tambyah, PA
Lye, DC
De, PP
Lin, RTP
Chew, KL
Yin, M
Lee, TH
Yilmaz, M
Cakmak, R
Alenazi, TH
Arabi, YM
Falcone, M
Bassetti, M
Righi, E
Rogers, BA
Kanj, SS
Bhally, H
Iredell, J
Mendelson, M
Boyles, TH
Looke, DFM
Runnegar, NJ
Miyakis, S
Walls, G
Khamis, MAI
Zikri, A
Crowe, A
Ingram, PR
Daneman, N
Griffin, P
Athan, EugeneORCID iD for Athan, Eugene orcid.org/0000-0001-9838-6471
Roberts, L
Beatson, SA
Peleg, AY
Cottrell, K
Bauer, MJ
Tan, E
Chaw, K
Nimmo, GR
Harris-Brown, T
Harris, PNA
MERINO Trial Investigators
Australasian Society for Infectious Disease Clinical Research Network (ASID-CDN)
Journal name Clinical Infectious Diseases
Start page 1
End page 9
Total pages 9
Publisher Oxford University Press
Place of publication Oxford, Eng.
Publication date 2020-10-27
ISSN 1058-4838
1537-6591
Keyword(s) Bloodstream infection
Extended spectrum beta-lactamase
Meropenem
Piperacillin-tazobactam
MERINO Trial Investigators and the Australasian Society for Infectious Disease Clinical Research Network (ASID-CRN)
Summary Abstract 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 β-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.
Notes In Press
Language eng
DOI 10.1093/cid/ciaa1479
Indigenous content off
Field of Research 110399 Clinical Sciences not elsewhere classified
06 Biological Sciences
11 Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Persistent URL http://hdl.handle.net/10536/DRO/DU:30147867

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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