A Henderson1,2, D L Paterson1, M D Chatfield1, P A Tambyah3, D C Lye4,5,6, P P De7, R T P Lin7, K L Chew8, M Yin3, T H Lee4,5,6, M Yilmaz9, R Cakmak9, T H Alenazi10, Y M Arabi10, M Falcone11, M Bassetti12, E Righi13,14, B A Rogers15,16, S S Kanj17, H Bhally18, J Iredell19,20, M Mendelson21, T H Boyles21, D F M Looke2,22, N J Runnegar2,22, S Miyakis23,24,25, G Walls26, M A I Khamis27, A Zikri27, A Crowe28,29, P R Ingram30,31,32, N Daneman33, P Griffin22,34,35, E Athan36, L Roberts37, S A Beatson37, A Y Peleg38,39, K Cottrell1, M J Bauer1, E Tan1, K Chaw40,41,42, G R Nimmo43, T Harris-Brown1, P N A Harris1,43. 1. University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia. 2. Infection Management Services, Princess Alexandra Hospital, Brisbane, Australia. 3. Department of Infectious Diseases, National University Hospital, Singapore. 4. Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 5. Department of Infectious Diseases, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore. 6. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. 7. Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore. 8. Division of Microbiology, National University Hospital, Singapore. 9. Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey. 10. King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. 11. Division of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Pisa, Italy. 12. Infectious Diseases Clinic, Department of Health Sciences, University of Genoa and Ospedale Policlinico San Martino Genoa, Italy. 13. Infectious Diseases Clinic, Department of Medicine University of Udine and Santa Maria Misericordia Hospital, Udine, Italy. 14. Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Verona, Italy. 15. Monash University, Centre for Inflammatory Diseases, Victoria, Australia. 16. Monash Infectious Diseases, Monash Health, Victoria, Australia. 17. Department of Internal Medicine, Division of Infectious Diseases, American University of Beirut Medical Center, Beirut, Lebanon. 18. Department of Medicine and Infectious Diseases, North Shore Hospital, Auckland, New Zealand. 19. Marie Bashir Institute for Infectious Disease and Biosecurity, University of Sydney, Sydney, Australia. 20. Centre for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, Australia. 21. Division of Infectious Diseases & HIV Medicine, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa. 22. University of Queensland, Brisbane, Australia. 23. School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia. 24. Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia. 25. Department of Infectious Diseases, Wollongong Hospital, Wollongong, New South Wales, Australia. 26. Department of Infectious Diseases, Middlemore Hospital, Auckland, New Zealand. 27. King Fahad Specialist Hospital, Dammam, Saudi Arabia. 28. Department of Infectious Diseases, St Vincent's Hospital, Melbourne, Australia. 29. Department of Microbiology, St Vincent's Hospital, Melbourne, Australia. 30. School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, Australia. 31. Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch, Australia. 32. Department of Microbiology, PathWest Laboratory Medicine, Perth, Western Australia. 33. Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada. 34. Department of Medicine and Infectious Diseases, Mater Hospital and Mater Medical Research Institute, Brisbane, Australia. 35. QIMR Berghofer, Brisbane, Queensland, Australia. 36. Department of Infectious Diseases, Barwon Health and Deakin University, Geelong, Victoria, Australia. 37. Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, University of Queensland, Queensland, Australia. 38. Infection & Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia. 39. Department of Microbiology, Monash University, Clayton, Australia. 40. Department of Microbiology, Pathology Queensland, Toowoomba Laboratory, Australia. 41. Department of Microbiology, Mater Pathology, Australia. 42. Infectious Diseases Department, Redcliffe Hospital, Australia. 43. Department of Microbiology, Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Australia.
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.
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.
Authors: Kamrul Islam; Fekade B Sime; Steven C Wallis; Michelle J Bauer; Saiyuri Naicker; Hayoung Won; Hosam M Zowawi; Md Abu Choudhury; Tahmina Shirin; Zakir H Habib; Patrick N A Harris; Meerjady S Flora; Jason A Roberts Journal: Antimicrob Agents Chemother Date: 2022-08-04 Impact factor: 5.938
Authors: Adam G Stewart; David L Paterson; Barnaby Young; David C Lye; Joshua S Davis; Kellie Schneider; Mesut Yilmaz; Rumeysa Dinleyici; Naomi Runnegar; Andrew Henderson; Sophia Archuleta; Shirin Kalimuddin; Brian M Forde; Mark D Chatfield; Michelle J Bauer; Jeffrey Lipman; Tiffany Harris-Brown; Patrick N A Harris Journal: Open Forum Infect Dis Date: 2021-08-02 Impact factor: 3.835