Cefazolin for Methicillin-Susceptible Staphylococcus aureus Bacteremia
(2026) In The New England journal of medicine 394(23). p.2329-2339- Abstract
BACKGROUND: Staphylococcus aureus bacteremia is associated with high mortality. Whether cefazolin or an antistaphylococcal penicillin should be preferred for the treatment of methicillin-susceptible S. aureus bacteremia is unclear.
METHODS: In an ongoing international Bayesian adaptive platform trial, we conducted an open-label, randomized comparison of cefazolin with an antistaphylococcal penicillin (flucloxacillin or cloxacillin) in adult patients with penicillin-resistant, methicillin-susceptible S. aureus bacteremia. The primary outcome, which was evaluated with a hierarchical Bayesian logistic-regression model, was death from any cause within 90 days after enrollment in the platform. We assessed the posterior probability of... (More)
BACKGROUND: Staphylococcus aureus bacteremia is associated with high mortality. Whether cefazolin or an antistaphylococcal penicillin should be preferred for the treatment of methicillin-susceptible S. aureus bacteremia is unclear.
METHODS: In an ongoing international Bayesian adaptive platform trial, we conducted an open-label, randomized comparison of cefazolin with an antistaphylococcal penicillin (flucloxacillin or cloxacillin) in adult patients with penicillin-resistant, methicillin-susceptible S. aureus bacteremia. The primary outcome, which was evaluated with a hierarchical Bayesian logistic-regression model, was death from any cause within 90 days after enrollment in the platform. We assessed the posterior probability of the noninferiority of cefazolin to flucloxacillin or cloxacillin (with the criterion for noninferiority prespecified as an adjusted odds ratio of <1.2, which approximates an absolute difference in mortality of <2.5 percentage points if mortality in the antistaphylococcal-penicillin group is 15%), as well as the posterior probability of superiority (with the criterion of an adjusted odds ratio of <1.0). Secondary safety outcomes included the development of acute kidney injury within 14 days.
RESULTS: This domain of the ongoing trial was conducted between February 17, 2022, and August 7, 2024, by which time the criterion for noninferiority had been met. Mortality at 90 days among adults who could be evaluated was 15.0% (97 deaths among 645 patients) in the cefazolin group and 17.0% (109 deaths among 642 patients) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.81; 95% credible interval, 0.59 to 1.12; probability of noninferiority, 99.2%; probability of superiority, 89.8%). Acute kidney injury occurred in 92 of 660 patients (13.9%) in the cefazolin group, as compared with 127 of 648 (19.6%) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.67; 95% credible interval, 0.50 to 0.89; probability of superiority, 99.7%).
CONCLUSIONS: In patients with methicillin-susceptible S. aureus bacteremia, cefazolin was noninferior to flucloxacillin or cloxacillin with respect to 90-day mortality and was associated with a lower incidence of acute kidney injury. (Funded by the National Health and Medical Research Council and others; SNAP ClinicalTrials.gov number, NCT05137119.).
(Less)
- author
- Lee, Todd C
; Barina, Lauren A
; Walls, Genevieve
; Goodman, Anna L
; Yahav, Dafna
; Cheng, Matthew P
; Bonten, Marc
; Bowen, Asha C
; Boyles, Tom
; Daneman, Nick
; Ekkelenkamp, Miquel B
; Ghanem-Zoubi, Nesrin
; Hensgens, Marjolein P M
; Jager, Nynke G L
; Kaasch, Achim J
; Kouijzer, Ilse J E
; Lewis, Roger J
; Lumley, Thomas
; Lye, David C
; McDonald, Emily G
; McKew, Genevieve
; McLean, Alistair R D
; McMullan, Brendan J
; McQuilten, Zoe K
; Morpeth, Susan C
; Roberts, Jason A
; Robinson, J Owen
; Saito, Hiroki
; Scarborough, Matthew
; Ten Oever, Jaap
; Turner, Rebecca M
; Tverring, Jonas
LU
; van Hal, Sebastiaan J
; Webb, Steve A
; Whiteway, Lynda M
; Arias, Cesar A
; Henderson, Andrew
; Heriot, George S
; Snelling, Tom L
; Afra, Kevin
; Ali, Shabinah S
; Amit, Sharon
; Anagnostou, Nicholas A
; Archuleta, Sophia
; Aston, Stephen J
; Athan, Eugene
; Baharav, Nadav
; Bai, Anthony D
; Barber, Bridget E
; Baskaran, Abinayah
and Tong, Steven Y.C.
(Less) - author collaboration
- organization
- publishing date
- 2026-06-17
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Aged, Female, Humans, Male, Middle Aged, Anti-Bacterial Agents/therapeutic use, Bacteremia/drug therapy, Bayes Theorem, Cefazolin/therapeutic use, Cloxacillin/therapeutic use, First Generation Cephalosporins/adverse effects, Floxacillin/therapeutic use, Staphylococcal Infections/drug therapy, Staphylococcus aureus/drug effects, Incidence, Acute Kidney Injury/chemically induced, Treatment Outcome
- in
- The New England journal of medicine
- volume
- 394
- issue
- 23
- pages
- 2329 - 2339
- publisher
- Massachussetts Medical Society
- external identifiers
-
- pmid:42308484
- ISSN
- 0028-4793
- DOI
- 10.1056/NEJMoa2506905
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2026 Massachusetts Medical Society.
- id
- 06075e0a-97da-49f5-b0ec-9c2c587271e1
- date added to LUP
- 2026-06-23 10:17:45
- date last changed
- 2026-06-23 10:17:45
@article{06075e0a-97da-49f5-b0ec-9c2c587271e1,
abstract = {{<p>BACKGROUND: Staphylococcus aureus bacteremia is associated with high mortality. Whether cefazolin or an antistaphylococcal penicillin should be preferred for the treatment of methicillin-susceptible S. aureus bacteremia is unclear.</p><p>METHODS: In an ongoing international Bayesian adaptive platform trial, we conducted an open-label, randomized comparison of cefazolin with an antistaphylococcal penicillin (flucloxacillin or cloxacillin) in adult patients with penicillin-resistant, methicillin-susceptible S. aureus bacteremia. The primary outcome, which was evaluated with a hierarchical Bayesian logistic-regression model, was death from any cause within 90 days after enrollment in the platform. We assessed the posterior probability of the noninferiority of cefazolin to flucloxacillin or cloxacillin (with the criterion for noninferiority prespecified as an adjusted odds ratio of <1.2, which approximates an absolute difference in mortality of <2.5 percentage points if mortality in the antistaphylococcal-penicillin group is 15%), as well as the posterior probability of superiority (with the criterion of an adjusted odds ratio of <1.0). Secondary safety outcomes included the development of acute kidney injury within 14 days.</p><p>RESULTS: This domain of the ongoing trial was conducted between February 17, 2022, and August 7, 2024, by which time the criterion for noninferiority had been met. Mortality at 90 days among adults who could be evaluated was 15.0% (97 deaths among 645 patients) in the cefazolin group and 17.0% (109 deaths among 642 patients) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.81; 95% credible interval, 0.59 to 1.12; probability of noninferiority, 99.2%; probability of superiority, 89.8%). Acute kidney injury occurred in 92 of 660 patients (13.9%) in the cefazolin group, as compared with 127 of 648 (19.6%) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.67; 95% credible interval, 0.50 to 0.89; probability of superiority, 99.7%).</p><p>CONCLUSIONS: In patients with methicillin-susceptible S. aureus bacteremia, cefazolin was noninferior to flucloxacillin or cloxacillin with respect to 90-day mortality and was associated with a lower incidence of acute kidney injury. (Funded by the National Health and Medical Research Council and others; SNAP ClinicalTrials.gov number, NCT05137119.).</p>}},
author = {{Lee, Todd C and Barina, Lauren A and Walls, Genevieve and Goodman, Anna L and Yahav, Dafna and Cheng, Matthew P and Bonten, Marc and Bowen, Asha C and Boyles, Tom and Daneman, Nick and Ekkelenkamp, Miquel B and Ghanem-Zoubi, Nesrin and Hensgens, Marjolein P M and Jager, Nynke G L and Kaasch, Achim J and Kouijzer, Ilse J E and Lewis, Roger J and Lumley, Thomas and Lye, David C and McDonald, Emily G and McKew, Genevieve and McLean, Alistair R D and McMullan, Brendan J and McQuilten, Zoe K and Morpeth, Susan C and Roberts, Jason A and Robinson, J Owen and Saito, Hiroki and Scarborough, Matthew and Ten Oever, Jaap and Turner, Rebecca M and Tverring, Jonas and van Hal, Sebastiaan J and Webb, Steve A and Whiteway, Lynda M and Arias, Cesar A and Henderson, Andrew and Heriot, George S and Snelling, Tom L and Afra, Kevin and Ali, Shabinah S and Amit, Sharon and Anagnostou, Nicholas A and Archuleta, Sophia and Aston, Stephen J and Athan, Eugene and Baharav, Nadav and Bai, Anthony D and Barber, Bridget E and Baskaran, Abinayah and Tong, Steven Y.C.}},
issn = {{0028-4793}},
keywords = {{Aged; Female; Humans; Male; Middle Aged; Anti-Bacterial Agents/therapeutic use; Bacteremia/drug therapy; Bayes Theorem; Cefazolin/therapeutic use; Cloxacillin/therapeutic use; First Generation Cephalosporins/adverse effects; Floxacillin/therapeutic use; Staphylococcal Infections/drug therapy; Staphylococcus aureus/drug effects; Incidence; Acute Kidney Injury/chemically induced; Treatment Outcome}},
language = {{eng}},
month = {{06}},
number = {{23}},
pages = {{2329--2339}},
publisher = {{Massachussetts Medical Society}},
series = {{The New England journal of medicine}},
title = {{Cefazolin for Methicillin-Susceptible Staphylococcus aureus Bacteremia}},
url = {{http://dx.doi.org/10.1056/NEJMoa2506905}},
doi = {{10.1056/NEJMoa2506905}},
volume = {{394}},
year = {{2026}},
}