Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2025
Cefazolin vs. antistaphylococcal penicillins for the treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a systematic review and meta-analysis.
СтатьяСистематический обзорМетаанализСравнительное исследованиеНазвание и аннотация: Перевод в очереди
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Prosty Connor, Noutsios Dean, Lee Todd C, Daneman Nick, Davis Joshua S, Jager Nynke G L, Ghanem-Zoubi Nesrin, Goodman Anna L, Kaasch Achim J, Kouijzer Ilse, McMullan Brendan J, McDonald Emily G, Tong Steven Y C, Ong Sean W X, Staphylococcus aureus Network Adaptive Platform MSSA/PSSA domain specific working group
Аннотация
BACKGROUND: There is debate on whether cefazolin or antistaphylococcal penicillins should be the first-line treatment for methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. Ongoing trials are investigating whether cefazolin is non-inferior to (flu)cloxacillin, but it remains uncertain whether these findings apply to other antistaphylococcal penicillins.
OBJECTIVES: We conducted a systematic review and meta-analysis comparing cefazolin with each of the individual antistaphylococcal penicillins for MSSA bacteraemia.
METHODS: Data sources: We updated a 2019 systematic review but specifically focused on evaluating outcomes by individual antistaphylococcal penicillins.
STUDY ELIGIBILITY CRITERIA: Study eligibility criteria include comparative observational studies.
PARTICIPANTS: Participants include patients with MSSA bacteraemia.
INTERVENTIONS: Interventions include cefazolin vs. the antistaphylococcal penicillins.
ASSESSMENT OF RISK OF BIAS: Assessment of risk of bias involved the risk of bias in non-randomized studies of interventions tool.
METHODS OF DATA SYNTHESIS: The primary outcome was 30-day all-cause mortality and we assessed for non-inferiority of cefazolin using a pre-specified non-inferiority margin of a pooled OR <1.2 using raw unadjusted data. Secondary outcomes were 90-day mortality, treatment-related adverse events (TRAEs), discontinuation due to toxicity, and nephrotoxicity.
RESULTS: No randomized data have been published. A total of 30 observational studies at moderate or high risk of bias were included, which comprised 3869 patients who received cefazolin and 11 644 patients who received antistaphylococcal penicillins (flucloxacillin = 6721, unspecified = 2440, nafcillin = 1305, cloxacillin = 1258, and oxacillin = 120). Cefazolin was associated with a reduced odds of 30-day all-cause mortality (OR = 0.73, 95% CI: 0.62-0.85) compared with antistaphylococcal penicillins, meeting pre-specified non-inferiority. This effect was consistent vs. flucloxacillin (OR = 0.92, 95% CI: 0.73-1.16), nafcillin (OR = 0.58, 95% CI: 0.28-1.17), cloxacillin (OR = 0.42, 95% CI: 0.11-1.58), and oxacillin (OR = 0.31, 95% CI: 0.03-2.75). Point estimates favoured cefazolin for 90-day mortality, TRAEs, nephrotoxicity, and discontinuation due to toxicity overall and in each comparison with individual antistaphylococcal penicillins, except for TRAEs vs. cloxacillin.
DISCUSSION: In moderate-to low-quality observational data, cefazolin was non-inferior for mortality and potentially superior for safety as compared with antistaphylococcal penicillins overall and across most individual comparisons.
OBJECTIVES: We conducted a systematic review and meta-analysis comparing cefazolin with each of the individual antistaphylococcal penicillins for MSSA bacteraemia.
METHODS: Data sources: We updated a 2019 systematic review but specifically focused on evaluating outcomes by individual antistaphylococcal penicillins.
STUDY ELIGIBILITY CRITERIA: Study eligibility criteria include comparative observational studies.
PARTICIPANTS: Participants include patients with MSSA bacteraemia.
INTERVENTIONS: Interventions include cefazolin vs. the antistaphylococcal penicillins.
ASSESSMENT OF RISK OF BIAS: Assessment of risk of bias involved the risk of bias in non-randomized studies of interventions tool.
METHODS OF DATA SYNTHESIS: The primary outcome was 30-day all-cause mortality and we assessed for non-inferiority of cefazolin using a pre-specified non-inferiority margin of a pooled OR <1.2 using raw unadjusted data. Secondary outcomes were 90-day mortality, treatment-related adverse events (TRAEs), discontinuation due to toxicity, and nephrotoxicity.
RESULTS: No randomized data have been published. A total of 30 observational studies at moderate or high risk of bias were included, which comprised 3869 patients who received cefazolin and 11 644 patients who received antistaphylococcal penicillins (flucloxacillin = 6721, unspecified = 2440, nafcillin = 1305, cloxacillin = 1258, and oxacillin = 120). Cefazolin was associated with a reduced odds of 30-day all-cause mortality (OR = 0.73, 95% CI: 0.62-0.85) compared with antistaphylococcal penicillins, meeting pre-specified non-inferiority. This effect was consistent vs. flucloxacillin (OR = 0.92, 95% CI: 0.73-1.16), nafcillin (OR = 0.58, 95% CI: 0.28-1.17), cloxacillin (OR = 0.42, 95% CI: 0.11-1.58), and oxacillin (OR = 0.31, 95% CI: 0.03-2.75). Point estimates favoured cefazolin for 90-day mortality, TRAEs, nephrotoxicity, and discontinuation due to toxicity overall and in each comparison with individual antistaphylococcal penicillins, except for TRAEs vs. cloxacillin.
DISCUSSION: In moderate-to low-quality observational data, cefazolin was non-inferior for mortality and potentially superior for safety as compared with antistaphylococcal penicillins overall and across most individual comparisons.