SAFO
Trial question
What is the role of cloxacillin plus fosfomycin in patients with MSSA bacteremia?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
30.0% female
70.0% male
N = 214
214 patients (64 female, 150 male).
Inclusion criteria: hospitalized adult patients with MSSA bacteremia.
Key exclusion criteria: severe clinical status with expected death in < 24 hours; severe liver cirrhosis; moderate-to-severe chronic HF; suspicion of prosthetic valve endocarditis; history of significant allergy to β-lactam antibiotics or fosfomycin.
Interventions
N=104 cloxacillin plus fosfomycin (cloxacillin sodium IV 2 g every 4 hours and fosfomycin sodium 3 g every 6 hours).
N=110 cloxacillin alone (cloxacillin sodium IV 2 g every 4 hours).
Primary outcome
Treatment success at day 7
79.8%
74.5%
79.8 %
59.8 %
39.9 %
19.9 %
0.0 %
Cloxacillin plus
fosfomycin
Cloxacillin
alone
No significant
difference ↔
No significant difference in treatment success at day 7 (79.8% vs. 74.5%; AD 5.3%, 95% CI -5.95 to 16.48).
Secondary outcomes
No significant difference in all-cause mortality at day 7 (3.8% vs. 0.9%; AD 2.9%, 95% CI -2.1 to 7.97).
No significant difference in all-cause mortality at end of therapy (9.6% vs. 12.7%; ARD -3.1, 95% CI -11.53 to 5.31).
No significant difference in persistent bacteremia at day 7 (2.2% vs. 4.1%; ARD -1.9, 95% CI -7.97 to 4.16).
Safety outcomes
No significant difference in serious adverse events leading to discontinuation of therapy.
Conclusion
In hospitalized adult patients with MSSA bacteremia, cloxacillin plus fosfomycin was not superior to cloxacillin alone with respect to treatment success at day 7.
Reference
Sara Grillo, Miquel Pujol, Josep M Miró et al. Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial. Nat Med. 2023 Oct;29(10):2518-2525.
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