Comparable Effectiveness of Cefuroxime and Piperacillin-Tazobactam as Empirical Therapy for Methicillin-Susceptible Staphylococcus aureus Bacteremia

ABSTRACT Our objective was to examine whether empirical antimicrobial therapy (EAT) against methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) with piperacillin-tazobactam (TZP), cefuroxime or combination therapy with one of these was differentially associated with 7-, 30-, and 90- da...

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Main Authors: Robert Strengen Bigseth, Håkon Sandholdt, Andreas Petersen, Christian Østergaard, Thomas Benfield, Louise Thorlacius-Ussing
Format: Article
Language:English
Published: American Society for Microbiology 2022-06-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.01530-21
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author Robert Strengen Bigseth
Håkon Sandholdt
Andreas Petersen
Christian Østergaard
Thomas Benfield
Louise Thorlacius-Ussing
author_facet Robert Strengen Bigseth
Håkon Sandholdt
Andreas Petersen
Christian Østergaard
Thomas Benfield
Louise Thorlacius-Ussing
author_sort Robert Strengen Bigseth
collection DOAJ
description ABSTRACT Our objective was to examine whether empirical antimicrobial therapy (EAT) against methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) with piperacillin-tazobactam (TZP), cefuroxime or combination therapy with one of these was differentially associated with 7-, 30-, and 90- day all-cause mortality or MS-SAB relapse. A multicenter retrospective cohort study of adults with MS-SAB from 2009 through 2018 was used, and 7-, 30-, 90-day mortality and relapse within 90 days were assessed and expressed as hazard ratio (HR) with a 95% confidence interval (95% CI) using Cox proportional hazard regression analysis. Matching of the two monotherapy groups was performed using propensity score matching. In total, 1158 MS-SAB cases were included and received one of three EAT regimens: TZP (n = 429), cefuroxime (n = 337), or TZP or cefuroxime with one or more additional effective antimicrobial (n = 392). The overall 30-day mortality was 28.0% (25.5 to 30.3%). After adjustment and matching, there was no significant difference in 7-, 30-, or 90-day mortality between the therapy groups. The matched HR of death was 0.81 (95% CI, 0.38 to 1.76) at 7 days, 0.82 (95% CI, 0.47 to 1.46) at 30 days, and 0.81 (95% CI, 0.50 to 1.32) at 90 days for TZP compared with cefuroxime. Adjusted HR of 90-day relapse was insignificant between the three therapy groups: TZP: 1.55 (95% CI, 0.54 to 4.43); combination therapy: 1.73 (95% CI, 0.62 to 4.80) compared to cefuroxime. There was no significant difference in 7-, 30-, or 90-day mortality or relapse between MS-SAB patients treated with empirical TZP or cefuroxime after adjustment and matching of covariables. IMPORTANCE This multicenter retrospective matched cohort study evaluated the effect of empirical antimicrobial therapy on the clinical outcome of methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) in >1100 adult patients. To the best of our knowledge, this is the largest study to date evaluating the effect of empirical treatment on the MS-SAB outcome. Importantly, the study found no significant difference in either short- or long-term mortality nor relapse between patients with MS-SAB receiving empirical treatment with cefuroxime or piperacillin-tazobactam. As such, this study provides crucial contemporary data supporting the widespread clinical practice of initiating empirical antimicrobial therapy of sepsis with β-lactam-β-lactamase-inhibitor.
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spelling doaj.art-be562732027c442dbd665733fbc3218d2022-12-22T00:17:50ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-06-0110310.1128/spectrum.01530-21Comparable Effectiveness of Cefuroxime and Piperacillin-Tazobactam as Empirical Therapy for Methicillin-Susceptible Staphylococcus aureus BacteremiaRobert Strengen Bigseth0Håkon Sandholdt1Andreas Petersen2Christian Østergaard3Thomas Benfield4Louise Thorlacius-Ussing5CREDID (Center of Research & Disruption of Infectious Diseases), Department of Infectious Diseases, Copenhagen University Hospital, Amager and Hvidovre, Hvidovre, DenmarkCREDID (Center of Research & Disruption of Infectious Diseases), Department of Infectious Diseases, Copenhagen University Hospital, Amager and Hvidovre, Hvidovre, DenmarkReference Laboratory for Antimicrobial Resistance, Statens Serum Institut, Copenhagen, DenmarkDepartment of Clinical Microbiology, Copenhagen University Hospital, Amager and Hvidovre, Hvidovre, DenmarkCREDID (Center of Research & Disruption of Infectious Diseases), Department of Infectious Diseases, Copenhagen University Hospital, Amager and Hvidovre, Hvidovre, DenmarkCREDID (Center of Research & Disruption of Infectious Diseases), Department of Infectious Diseases, Copenhagen University Hospital, Amager and Hvidovre, Hvidovre, DenmarkABSTRACT Our objective was to examine whether empirical antimicrobial therapy (EAT) against methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) with piperacillin-tazobactam (TZP), cefuroxime or combination therapy with one of these was differentially associated with 7-, 30-, and 90- day all-cause mortality or MS-SAB relapse. A multicenter retrospective cohort study of adults with MS-SAB from 2009 through 2018 was used, and 7-, 30-, 90-day mortality and relapse within 90 days were assessed and expressed as hazard ratio (HR) with a 95% confidence interval (95% CI) using Cox proportional hazard regression analysis. Matching of the two monotherapy groups was performed using propensity score matching. In total, 1158 MS-SAB cases were included and received one of three EAT regimens: TZP (n = 429), cefuroxime (n = 337), or TZP or cefuroxime with one or more additional effective antimicrobial (n = 392). The overall 30-day mortality was 28.0% (25.5 to 30.3%). After adjustment and matching, there was no significant difference in 7-, 30-, or 90-day mortality between the therapy groups. The matched HR of death was 0.81 (95% CI, 0.38 to 1.76) at 7 days, 0.82 (95% CI, 0.47 to 1.46) at 30 days, and 0.81 (95% CI, 0.50 to 1.32) at 90 days for TZP compared with cefuroxime. Adjusted HR of 90-day relapse was insignificant between the three therapy groups: TZP: 1.55 (95% CI, 0.54 to 4.43); combination therapy: 1.73 (95% CI, 0.62 to 4.80) compared to cefuroxime. There was no significant difference in 7-, 30-, or 90-day mortality or relapse between MS-SAB patients treated with empirical TZP or cefuroxime after adjustment and matching of covariables. IMPORTANCE This multicenter retrospective matched cohort study evaluated the effect of empirical antimicrobial therapy on the clinical outcome of methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) in >1100 adult patients. To the best of our knowledge, this is the largest study to date evaluating the effect of empirical treatment on the MS-SAB outcome. Importantly, the study found no significant difference in either short- or long-term mortality nor relapse between patients with MS-SAB receiving empirical treatment with cefuroxime or piperacillin-tazobactam. As such, this study provides crucial contemporary data supporting the widespread clinical practice of initiating empirical antimicrobial therapy of sepsis with β-lactam-β-lactamase-inhibitor.https://journals.asm.org/doi/10.1128/spectrum.01530-21S. aureusbacteremiasepsisempirical therapypiperacillin-tazobactampip-tazo
spellingShingle Robert Strengen Bigseth
Håkon Sandholdt
Andreas Petersen
Christian Østergaard
Thomas Benfield
Louise Thorlacius-Ussing
Comparable Effectiveness of Cefuroxime and Piperacillin-Tazobactam as Empirical Therapy for Methicillin-Susceptible Staphylococcus aureus Bacteremia
Microbiology Spectrum
S. aureus
bacteremia
sepsis
empirical therapy
piperacillin-tazobactam
pip-tazo
title Comparable Effectiveness of Cefuroxime and Piperacillin-Tazobactam as Empirical Therapy for Methicillin-Susceptible Staphylococcus aureus Bacteremia
title_full Comparable Effectiveness of Cefuroxime and Piperacillin-Tazobactam as Empirical Therapy for Methicillin-Susceptible Staphylococcus aureus Bacteremia
title_fullStr Comparable Effectiveness of Cefuroxime and Piperacillin-Tazobactam as Empirical Therapy for Methicillin-Susceptible Staphylococcus aureus Bacteremia
title_full_unstemmed Comparable Effectiveness of Cefuroxime and Piperacillin-Tazobactam as Empirical Therapy for Methicillin-Susceptible Staphylococcus aureus Bacteremia
title_short Comparable Effectiveness of Cefuroxime and Piperacillin-Tazobactam as Empirical Therapy for Methicillin-Susceptible Staphylococcus aureus Bacteremia
title_sort comparable effectiveness of cefuroxime and piperacillin tazobactam as empirical therapy for methicillin susceptible staphylococcus aureus bacteremia
topic S. aureus
bacteremia
sepsis
empirical therapy
piperacillin-tazobactam
pip-tazo
url https://journals.asm.org/doi/10.1128/spectrum.01530-21
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