Effectiveness and safety of cefazolin vs antistaphylococcal penicillins for methicillin-susceptible Staphylococcus aureus bacteremia: a multicenter real-world evaluation using the international TriNetX database
Abstract
Objectives: This study aimed to evaluate the effectiveness and safety of cefazolin versus antistaphylococcal penicillins (ASPs) in the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. Methods: This phase IV, retrospective, comparative-effectiveness, multicentre study used data extracted from the international TriNetX analytics platform. Eligible patients developed monomicrobial MSSA bacteraemia during hospitalisation between January 1, 2015, and December 31, 2025, and received treatment with either cefazolin or ASPs. The primary outcome was all-cause mortality within 90 days. Safety outcomes included Clostridioides difficile infection within 90 days and renal, liver, allergic, and haematological disorders within 30 days. Survival analyses were conducted after propensity score matching. Results: Among 110,275 patients with MSSA bacteraemia identified, 3,908 (3.5%) met the inclusion criteria. After propensity score matching, 1,954 patients were included in each group. Treatment with cefazolin was associated with significantly reduced all-cause mortality within 90 days (9.7% versus 14.7%; HR = 0.620 [0.515–0.748]). Among the safety outcomes, Clostridioides difficile infection occurred less frequently in the cefazolin group (4.9% versus 7.20%; HR = 0.631 [0.482–0.827]). Conclusion: This real-world evaluation using the international TriNetX database suggests that compared with ASPs, cefazolin is more effective and safer for the management of MSSA bacteraemia. Trial registration: NCT07186894
Related
- Two novel Silviavirus phages with lytic activity against methicillin-resistant Staphylococcus aureus: genomic and phenotypic characterization
- Preserving Nanotherapy-Induced Allogeneic Murine Islet Graft Tolerance During Distal Methicillin-Resistant Staphylococcus aureus Skin Infection
- An unusual acyclic nor-triterpene derivative from Lacrymaria lacrymabunda mushroom active against methicillin-resistant Staphylococcus aureus (MRSA)
- Beta-lactam enhancement against methicillin-resistant Staphylococcus aureus by cell wall blockade is autolysis-dependent: a butyrolactone derivative as case in point
- A truncated nisin variant, lipidated at its C-terminus, displays improved stability and increased antibacterial activity against methicillin-resistant Staphylococcus aureus
BibTeX
@article{ramsamy2026effectiveness,
title = {{Effectiveness and safety of cefazolin vs antistaphylococcal penicillins for methicillin-susceptible Staphylococcus aureus bacteremia: a multicenter real-world evaluation using the international TriNetX database}},
author = {Natesan Ramsamy and Maïa Simon and Isabelle Adam and Gema Hernandez and Sarah Williford and Olivier Denquin and Céline Pulcini and Nathalie Thilly and Benjamin Lefèvre},
journal = {Antimicrobial Agents and Chemotherapy},
year = {2026},
month = sep,
doi = {10.1128/aac.01765-25},
url = {https://hal.science/hal-05756449v1},
note = {CC BY-NC-SA 4.0},
}
RIS
TY - JOUR
TI - Effectiveness and safety of cefazolin vs antistaphylococcal penicillins for methicillin-susceptible Staphylococcus aureus bacteremia: a multicenter real-world evaluation using the international TriNetX database
AU - Natesan Ramsamy
AU - Maïa Simon
AU - Isabelle Adam
AU - Gema Hernandez
AU - Sarah Williford
AU - Olivier Denquin
AU - Céline Pulcini
AU - Nathalie Thilly
AU - Benjamin Lefèvre
PY - 2026
DA - 2026/09/11
JO - Antimicrobial Agents and Chemotherapy
DO - 10.1128/aac.01765-25
UR - https://hal.science/hal-05756449v1
AB - Objectives: This study aimed to evaluate the effectiveness and safety of cefazolin versus antistaphylococcal penicillins (ASPs) in the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. Methods: This phase IV, retrospective, comparative-effectiveness, multicentre study used data extracted from the international TriNetX analytics platform. Eligible patients developed monomicrobial MSSA bacteraemia during hospitalisation between January 1, 2015, and December 31, 2025, and received treatment with either cefazolin or ASPs. The primary outcome was all-cause mortality within 90 days. Safety outcomes included Clostridioides difficile infection within 90 days and renal, liver, allergic, and haematological disorders within 30 days. Survival analyses were conducted after propensity score matching. Results: Among 110,275 patients with MSSA bacteraemia identified, 3,908 (3.5%) met the inclusion criteria. After propensity score matching, 1,954 patients were included in each group. Treatment with cefazolin was associated with significantly reduced all-cause mortality within 90 days (9.7% versus 14.7%; HR = 0.620 [0.515–0.748]). Among the safety outcomes, Clostridioides difficile infection occurred less frequently in the cefazolin group (4.9% versus 7.20%; HR = 0.631 [0.482–0.827]). Conclusion: This real-world evaluation using the international TriNetX database suggests that compared with ASPs, cefazolin is more effective and safer for the management of MSSA bacteraemia. Trial registration: NCT07186894
SN - 0066-4804
SN - 1098-6596
ER -