Preincision adjunctive prophylaxis for cesarean deliveries a systematic review and meta-analysis


      This study aimed to systematically review the relative effectiveness of preincision cefazolin with or without adjunctive prophylaxis (macrolides or metronidazole) vs cefazolin alone in decreasing the incidence of postcesarean delivery surgical site infections.

      Data Sources

      We performed a systematic search on PubMed, Ovid EMBASE, Google Scholar,, and the Cochrane Central Register of Controlled Trials from October 25, 2020, to November 25, 2020, to identify studies comparing cefazolin with adjunctive macrolides or metronidazole with cefazolin alone. The reference lists were reviewed, and a manual search of articles published after the last database search was performed.

      Study Eligibility Criteria

      Overall, 3 randomized controlled trials and 1 prospective observational study of reproductive-age women undergoing cesarean deliveries were included in the study. We excluded studies of women who were immunocompromised (eg, patients who were HIV positive) or women with a diagnosis of chorioamnionitis before cesarean delivery. All patients received first-line cefazolin (either cefazolin 1 g or 2 g). We compared preincision cefazolin alone with preincision cefazolin plus adjunctive therapy (500 mg, oral or intravenous formulations of azithromycin, metronidazole, or clarithromycin).


      A total of 6 review authors independently assessed the risk of bias for each study, using the Cochrane Risk of Bias criteria. Synthesis and further appraisal were done using the Grading of Recommendations, Assessment, Development, and Evaluation levels and the American College of Obstetricians and Gynecologists 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-effects models using the Review Manager 5 software (version 5.4.1).


      Overall, 3 randomized controlled trials and 1 prospective observational study representing 2613 women met the criteria for inclusion. Significant reductions in surgical site infections (relative risk, 0.46; 95% confidence interval, 0.34–0.63; 3 randomized controlled trials) and the duration of hospital stay (weighted mean difference, −1.46; 95% confidence interval, −2.21 to −0.71; 2 randomized controlled trials) were observed with preincision cefazolin and adjunctive prophylaxis compared with cefazolin alone. No significant difference was observed in maternal febrile morbidity (relative risk, 0.38; 95% confidence interval, 0.11–1.25; 2 randomized controlled trials).


      Our findings have provided evidence for the use of preincision adjunctive extended-spectrum prophylaxis with cefazolin over cefazolin alone. However, future investigations are required to establish the relative efficacies of different adjunctive antibiotic options.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Martin J.A.
        • Hamilton B.E.
        • Sutton P.D.
        • et al.
        Births: final data for 2005.
        Natl Vital Stat Rep. 2007; 56: 1-103
        • Reichman D.E.
        • Greenberg J.A.
        Reducing surgical site infections: a review.
        Rev Obstet Gynecol. 2009; 2: 212-221
        • Kawakita T.
        • Landy H.J.
        Surgical site infections after cesarean delivery: epidemiology, prevention and treatment.
        Matern Health Neonatol Perinatol. 2017; 3: 12
        • Haque M.
        • Sartelli M.
        • McKimm J.
        • Abu Bakar M.
        Health care-associated infections - an overview.
        Infect Drug Resist. 2018; 11: 2321-2333
        • Bratzler D.W.
        • Dellinger E.P.
        • Olsen K.M.
        • et al.
        Clinical practice guidelines for antimicrobial prophylaxis in surgery.
        Am J Health-Syst Pharm. 2013; 70: 195-283
        • Committee on Practice Bulletins-Obstetrics
        ACOG Practice Bulletin no. 199: use of prophylactic antibiotics in labor and delivery.
        Obstet Gynecol. 2018; 132: e103-e119
        • Meyer N.L.
        • Hosier K.V.
        • Scott K.
        • Lipscomb G.H.
        Cefazolin versus cefazolin plus metronidazole for antibiotic prophylaxis at cesarean section.
        South Med J. 2003; 96: 992-995
        • Tita A.T.N.
        • Szychowski J.M.
        • Boggess K.
        • et al.
        Adjunctive azithromycin prophylaxis for cesarean delivery.
        N Engl J Med. 2016; 375: 1231-1241
        • Martingano D.
        • Singh S.
        • Mitrofanova A.
        Azithromycin in the treatment of preterm prelabor rupture of membranes demonstrates a lower risk of chorioamnionitis and postpartum endometritis with an equivalent latency period compared with erythromycin antibiotic regimens.
        Infect Dis Obstet Gynecol. 2020; 2020: 2093530
        • Tita A.T.N.
        • Rouse D.J.
        • Blackwell S.
        • Saade G.R.
        • Spong C.Y.
        • Andrews W.W.
        Emerging concepts in antibiotic prophylaxis for cesarean delivery: a systematic review.
        Obstet Gynecol. 2009; 113: 675-682
        • Anderson D.J.
        • Podgorny K.
        • Berríos-Torres S.I.
        • et al.
        Strategies to prevent surgical site infections in acute care hospitals: 2014 update.
        Infect Control Hosp Epidemiol. 2014; 35: 605-627
        • Horan T.C.
        • Gaynes R.P.
        • Martone W.J.
        • Jarvis W.R.
        • Emori T.G.
        CDC definitions of nosocomial surgical site infections, 1992: a modification of CDC definitions of surgical wound infections.
        Infect Control Hosp Epidemiol. 1992; 13: 606-608
        • Boggess K.A.
        • Tita A.
        • Jauk V.
        • et al.
        Risk factors for postcesarean maternal infection in a trial of extended-spectrum antibiotic prophylaxis.
        Obstet Gynecol. 2017; 129: 481-485
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        • PRISMA Group
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        PLoS Med. 2009; 6e1000097
      1. Review Manager (RevMan) [Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

      2. Higgins J.P.T. Thomas J. Chandler J. Cumpston M. Li T. Page M.J. Welch V.A. Cochrane handbook for systematic reviews of interventions. 2nd edition. John Wiley & Sons, Chichester (UK)2019
        • Schünemann H.
        • Brożek J.
        • Guyatt G.
        • Oxman A.
        GRADE handbook.
        (Available at:) (Published. Accessed February 9, 2021)
        • Jyothi M.S.
        • Kalra J.K.
        • Arora A.
        • et al.
        Randomized controlled trial of cefazolin monotherapy versus cefazolin plus azithromycin single dose prophylaxis for cesarean deliveries: a developing country’s perspective.
        J Family Med Prim Care. 2019; 8: 3015-3021
        • Wright J.D.
        • Pawar N.
        • Gonzalez J.S.R.
        • et al.
        Scientific evidence underlying the American College of Obstetricians and Gynecologists’ practice bulletins.
        Obstet Gynecol. 2011; 118: 505-512
        • Pitt C.
        • Sanchez-Ramos L.
        • Kaunitz A.M.
        Adjunctive intravaginal metronidazole for the prevention of postcesarean endometritis: a randomized controlled trial.
        Obstet Gynecol. 2001; 98: 745-750
        • Lamp K.C.
        • Freeman C.D.
        • Klutman N.E.
        • Lacy M.K.
        Pharmacokinetics and pharmacodynamics of the nitroimidazole antimicrobials.
        Clin Pharmacokinet. 1999; 36: 353-373
        • Arnold K.C.
        • Flint C.J.
        • Arnold K.C.
        • Flint C.J.
        Use of prophylactic antibiotics in labor and delivery.
        Springer International Publishing, Basel, Switzerland2017: 129-133
        • Farmer N.
        • Hodgetts-Morton V.
        • Morris R.K.
        Are prophylactic adjunctive macrolides efficacious against caesarean section surgical site infection: a systematic review and meta-analysis.
        Eur J Obstet Gynecol Reprod Biol. 2020; 244: 163-171
        • Sullivan S.A.
        • Smith T.
        • Chang E.
        • Hulsey T.
        • Vandorsten J.P.
        • Soper D.
        Administration of cefazolin prior to skin incision is superior to cefazolin at cord clamping in preventing postcesarean infectious morbidity: a randomized, controlled trial.
        Am J Obstet Gynecol. 2007; 196: 455.e1-455.e5
        • Costantine M.M.
        • Rahman M.
        • Ghulmiyah L.
        • et al.
        Timing of perioperative antibiotics for cesarean delivery: a metaanalysis.
        Am J Obstet Gynecol. 2008; 199: 301.e1-301.e6