To systematically review the relative effectiveness of pre-incision cefazolin with or without adjunctive prophylaxis (macrolides or metronidazole), versus cefazolin alone, in decreasing the incidence of post-Cesarean surgical site infections.
We performed a systematic search of PubMed, Ovid EMBASE, Google Scholar, ClinicalTrials.gov and Cochrane Central Register of Controlled Trials from October 25 to November 25, 2020, to identify studies comparing cefazolin with adjunctive macrolides or metronidazole to cefazolin alone. Reference lists were reviewed, and a manual search of articles published after the last database search was conducted.
Three randomized controlled trials (RCTs) and one prospective observational study of reproductive age women undergoing cesarean sections were included in the study. We excluded studies with immunocompromised women (e.g., HIV-positive patients) or women with a diagnosis of chorioamnionitis before cesarean delivery. All patients received first-line cefazolin (either cefazolin 1g/2g). We compared pre-incision cefazolin alone with pre-incision cefazolin plus adjunctive therapy (500 mg, oral or intravenous formulations of azithromycin, metronidazole, or clarithromycin).
Six review authors independently assessed risk of bias for each study, using the Cochrane Risk of Bias criteria. Synthesis and further appraisal was done using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) levels and the American College of Obstetricians and Gynecologists (ACOG) appraisal guidelines. Disagreements were resolved by discussion. Treatment effects were evaluated using meta-analysis and pooled relative risks and 95% confidence intervals were generated using random-effect models using the Review Manager 5 Software, v. 5.4.1.
Three RCTs and one prospective observational study representing 2,613 women met criteria for inclusion. Significant reductions in surgical site infections (SSI) (RR 0.46; 95% CI 0.34, 0.63; 3 RCTs) and duration of hospital stay (WMD -1.46; 95% CI -2.21, -0.71, 2RCTs) were observed with pre-incision cefazolin and adjunctive prophylaxis, compared to cefazolin alone. No significant differences were observed in maternal febrile morbidity (RR 0.38, 95% CI 0.11 to 1.25; 2 RCTs).
PROSPERO, CRD 42021224288 ACOG LEVEL OF EVIDENCE: A.

Copyright © 2021. Published by Elsevier Inc.

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