Henderson, A.Paterson, D. L.Chatfield, M. D.Tambyah, P. A.Lye, D. C.De, P. P.Lin, R. T. P.Chew, K. L.Yin, M.Lee, T. H.Yılmaz, MesutÇakmak, RümeysaAlenazi, T. H.Arabi, Y. MFalcone, M.Bassetti, M.Righi, E.Ba, RogersKanj, S. S.Bhally, H.Iredell, J.Mendelson, M.Boyles, T. H.Looke, D. F. M.Runnegar, N. J.Miyakis, S.Walls, G.Ai Khamis, M.Zikri, A.Crowe, A.Ingram, P. R.Daneman, N. N.Griffin, P.Athan, E.Roberts, L.Beatson, S. A.Peleg, A. Y.Cottrell, K. K.Bauer, M. J.Tan, E.Chaw, K.Nimmo, G. R.Harris-Brown, T.Harris, P. N. A.2021-04-022021-04-022021Henderson, A., Paterson, D. L., Chatfield, M. D., Tambyah, P. A., Lye, D. C., De, P. P. ... Harris, P. N. A. (2021). 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, 73(11), e3842-e3850. https://doi.org/10.1093/cid/ciaa14791058-48381537-6591https://doi.org/10.1093/cid/ciaa1479https://hdl.handle.net/20.500.12511/6678Introduction: 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: 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam non-susceptible breakpoint (MIC > 16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% 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% - 10%) after excluding strains with piperacillin/tazobactam MIC values > 16 mg/L. Isolates co-harboring ESBL and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-mortality of 14% (95% CI 2% - 28%).Conclusion: After excluding non-susceptible strains, the 30-day mortality difference was 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 co-harboring ESBLs suggests meropenem remains the preferred choice for definitive treatment of ceftriaxone non-susceptible E. coli and Klebsiella.eninfo:eu-repo/semantics/closedAccessPiperacillin-TazobactamMeropenemExtended Spectrum Beta-LactamaseBloodstream InfectionArticle7311e3842e385010.1093/cid/ciaa1479Q1Q1