Combination therapy with fosfomycin for bacteraemia or endocarditis: a systematic review and meta-analysis of randomized trials.

BACKGROUND AND OBJECTIVES

Fosfomycin combination therapy for bacteraemia or endocarditis has been evaluated, but studies were limited by small sample sizes. We sought to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to establish robust efficacy and safety estimates of fosfomycin combination therapy in this patient population.

DATA SOURCES

MEDLINE, Embase, Cochrane Library and Web of Science databases were searched from inception through September 2024 (PROSPERO CRD42024583822).

STUDY ELIGIBILITY

RCTs comparing fosfomycin combination with standard-of-care antibiotics in patients with bacteraemia or endocarditis were included. Two independent reviewers screened studies for inclusion.

ASSESSMENT OF RISK OF BIAS

Risk of bias was assessed using the revised Cochrane RoB 2 tool.

DATA SYNTHESIS AND ANALYSIS

Treatment effects were estimated with pooled risk ratios (RRs) using random effects meta-analysis. Heterogeneity between studies was assessed with Cochran's Q-statistic and test.

RESULTS

Of 437 articles identified, three RCTs met inclusion criteria. Primary outcome of treatment success or cure was not meta-analysed due to clinical heterogeneity. Combination therapy did not significantly improve mortality (RR 0.85; 95% CI, 0.28-2.52;  = 27.8%) or persistent bacteraemia (RR 0.34; 95% CI, 0.04-2.59;  = 0%). Participants receiving combination therapy had more adverse events leading to treatment discontinuation, but this was not statistically significant (RR 1.84; 95% CI, 0.36-9.36;  = 18%).

CONCLUSIONS

In this meta-analysis of three RCTs, fosfomycin combination therapy for bacteraemia or endocarditis did not significantly improve patient outcomes and may be associated with higher rates of adverse events.