Metronidazole Plus Cefazolin Compared with Cefazolin Alone for Surgical Site Infection Prophylaxis in Patients...

To evaluate whether adding metronidazole to cefazolin for hysterectomy is more effective in the prevention of surgical site infection than the existing recommendation of cefazolin alone.

MEDLINE, ClinicalTrials.gov, EMBASE, Cochrane Library, and Web of Science were searched until October 16, 2024. The following words made up the search strategy: hysterectomy, cefazolin, metronidazole, and surgical site infection, and their variants.

Our search identified 987 studies, which were uploaded to Covidence for review management; 302 duplicates were automatically removed. A team of two reviewers screened 685 studies, and a third reviewer resolved conflicts. Studies were included if they 1) consisted of peer-reviewed research published between 1980 and 2024, 2) assessed patients undergoing hysterectomy by any route, 3) compared cefazolin to cefazolin and metronidazole, and 4) reported the primary outcome of surgical site infection within 30 days of the procedure.

Five studies with a total of 5838 participants met eligibility criteria; two were randomized controlled trials (RCTs) and three were observational (retrospective cohort studies). The two RCTs, each used vaginal metronidazole and the three observational studies each used intravenous (IV) metronidazole. The RCTs each found a qualitatively lower risk of surgical site infection (SSI) with vaginal metronidazole, compared to cefazolin alone (odds ratios [ORs] 0.28 and 0.43). Observational studies consistently found similar ORs for lower risk of SSI with IV metronidazole compared to cefazolin alone (OR range 0.40-0.63). These large effect sizes were statistically significant in only the two largest studies, reflecting the limited statistical power of several individual studies because of the low absolute frequencies of infections.

A systematic review of the literature shows evidence that the use of metronidazole in addition to cefazolin reduces the risk of surgical site infection after hysterectomy by any route and for any indication. Intravenous use of metronidazole in particular may be the preferred route of administration by both the patient and surgeon.