Grand Rounds

Can Clarithromycin Be Used as Antibiotic Prophylaxis for Cesarean When Azithromycin is Unavailable?

BACKGROUND AND PURPOSE:

There have been reported shortages of azithromycin due to the COVID-19 pandemic | Azithromycin can be considered for adjunct use in women undergoing cesarean section in addition to standard prophylaxis (usually cefazolin)
Martingano et al (PLoS ONE, 2020) evaluated safety and effectiveness of clarithromycin as an adjunct prophylactic alternative for patients undergoing non-elective cesarean delivery

Multi-center, prospective observational cohort study
Participants
- Women undergoing non-elective cesarean deliveries
Exposures
- Clarithromycin for adjunct surgical prophylaxis
- No macrolide antibiotic
Primary outcome
- Development of postpartum endometritis
Secondary outcomes
- Meconium-stained amniotic fluid at time of cesarean delivery
- Neonatal sepsis
- NICU admission
- Neonatal acute respiratory distress syndrome

240 patients
- Clarithromycin: 133 patients
- No macrolide prophylaxis: 107 patients
Patients who received clarithromycin had significantly lower rates of postpartum endometritis (P=0.025)
- Clarithromycin: 4.5%
- No macrolide prophylaxis: 11.2%
In unadjusted analysis, there was a significantly lower risk for developing endometritis in the clarithromycin group (P=0.040)
- 66% decreased risk (95% CI, 0.12 to 0.95)
Adjusted analysis: Risk for endometritis in the clarithromycin group was still significantly lower (P=0.034)
- 67% decreased risk (95% CI, 0.11 to 0.97)
In stratified analysis, there was a significantly decreased risk of endometritis with clarithromycin in
- Black women
  - Crude: 87% decreased risk (95% CI, 0.08 to 0.83; P=0.032)
  - Adjusted: 91% decreased risk (95% CI, 0.06 to 0.79; P=0.026)
- Women 18 to 29 years
  - Crude: 79% decreased risk (95% CI, 0.06 to 0.80; P=0.014)
  - Adjusted model: 75% decreased risk (95% CI, 0.06 to 0.94; P=0.028)
All other stratified analyses did not demonstrate significant differences in endometritis risk

Clarithromycin for antibiotic adjunct prophylaxis for cesarean delivery may be an acceptable substitute for azithromycin if it is unavailable
Authors recognize limitations, including lack of randomization
- Study did adjust for hospital site and indication for surgery but “not a substitute for randomized-controlled study design”
Decreased risk for endometritis with adjunctive use of clarithromycin was especially noted in Black women and women ages 18 to 29

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