Clarithromycin use for adjunct surgical prophylaxis before non-elective cesarean deliveries to adapt to azithromycin shortages in COVID-19 pandemic.

OBJECTIVE: This study aimed to evaluate safety and effectiveness of clarithromycin as adjunctive antibiotic prophylaxis for patients undergoing non-elective cesarean delivery in comparison with no macrolides, to adapt to azithromycin shortages in COVID-19 pandemic. STUDY DESIGN: We conducted a multi-center, prospective observational cohort study from March 23, 2020 through June 1, 2020. We followed all women receiving either clarithromycin or no macrolide antibiotic for adjunct surgical prophylaxis for non-elective cesarean deliveries. The primary outcome was development of postpartum endometritis. Secondary outcomes included meconium-stained amniotic fluid at time of cesarean delivery, neonatal sepsis, neonatal intensive care unit admission, and neonatal acute respiratory distress syndrome. All patients in this study were tested for SARS-CoV-2 infection and resulted negative. RESULTS: This study included 240 patients, with 133 patients receiving clarithromycin and 107 patients receiving no adjunct macrolide prophylaxis. Patients receiving clarithromycin were noted to have significantly lower rates of postpartum endometritis as compared to those who did not receive adjunct prophylaxis (4.5% versus 11.2%, p = 0.025). In crude (unadjusted) analysis, a significantly lower risk of developing endometritis was noted in the clarithromycin group as compared to the control group (66% decreased risk, 95% CI 0.12 to 0.95, p = 0.040). When adjusted for perceived confounders, a significant difference was again noted (67% decreased risk, 95% CI 0.11 to 0.97, p = 0.034). Stratified analysis of significantly different demographic factors including Black race, BMI, and age was performed. A significantly decreased risk of development of endometritis when taking clarithromycin versus no adjunct macrolide was noted for Black race women in crude and adjusted models (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). This was also noted for women aged 18-29 years in crude and adjusted models (crude: model, 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 yield significant differences in endometritis risk. CONCLUSION: Our study suggests that administration of clarithromycin for adjunctive surgical prophylaxis for non-elective cesarean deliveries may be a safe option that may provide suitable endometritis prophylaxis in cases where azithromycin is unavailable, as was the case during the start of COVID-19 pandemic, most especially for Black race women and women ages 18-29 years.

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.

Objective: To determine if antibiotic regimens including azithromycin versus erythromycin has an impact on pregnancy latency and development of clinical chorioamnionitis in the context of preterm prelabor rupture of membranes. Study Design. We conducted a prospective observational cohort study and followed all women receiving antibiotic regimens including either azithromycin or erythromycin in the context of preterm prelabor rupture of membranes. Primary outcomes were the duration of pregnancy latency period and development of chorioamnionitis. Secondary outcomes included neonatal sepsis with positive blood culture, cesarean delivery, postpartum endometritis, and meconium-stained amniotic fluid. Results: This study included 310 patients, with 142 receiving the azithromycin regimen and 168 receiving the erythromycin regimen. Patients receiving the azithromycin regimen had a statistically significant advantage in overall rates of clinical chorioamnionitis (13.4% versus 25%, p = 0.010), neonatal sepsis (4.9% versus 14.9%, p = 0.004), and postpartum endometritis (14.8% versus 31%, p = 0.001). In crude and adjusted models, when comparing the azithromycin group with the erythromycin group, a decreased risk was noted for the development of clinical chorioamnionitis, neonatal sepsis, and postpartum endometritis. Pregnancy latency by regimen was not significantly different in crude and adjusted models. Conclusion: Our study suggests that latency antibiotic regimens substituting azithromycin for erythromycin have lower rates and decreased risk of clinical chorioamnionitis, neonatal sepsis, and postpartum endometritis with no difference in pregnancy latency.

Daily gentamicin using ideal body weight demonstrates lower risk of postpartum endometritis and increased chance of successful outcome compared with traditional 8-hour dosing for the treatment of intrapartum chorioamnionitis.

Background: Clinical chorioamnionitis complicates approximately 1-4% of pregnancies overall. Although universal agreement does not exist regarding the antibiotic regimen of choice, most studies have evaluated intravenous ampicillin dosed at 2 g every 6 hours plus gentamicin dosed every 8 hours. Only three studies have examined daily gentamicin for the treatment of intrapartum chorioamnionitis and thus is insufficiently investigated. Objective: This study seeks to determine whether daily dosing of gentamicin using ideal body weight for the treatment of intrapartum chorioamnionitis is more or equivalently efficacious when compared to traditional 8-hour dosing regimens. Materials and methods: We conducted a retrospective cohort study and reviewed charts on all women receiving treatment for intrapartum chorioamnionitis, which included intravenous gentamicin daily dosing calculated using 5 mg/kg ideal body weight or receiving traditional every 8 hours dosing of gentamicin at two large academic centers. Our primary outcomes were resolution of infection following delivery without the development of maternal endometritis and/or neonatal sepsis. Baseline characteristics were compared between dosing groups using Welch two-sample t-tests for continuous variables, uncorrected X2 test and exact binomial 95% confidence intervals. We calculated the risk ratios of each outcome in the ideal versus traditional dosing groups using modified Poisson regression, both crude and adjusted. Adjusted models were controlled for variables determined to be potential confounders, which included BMI, diabetes mellitus, gestational blood pressure >140/90, group ß-Streptococcus status, race, advanced maternal age (>34 y), and parity. Results: The study included 500 patients with 255 patients receiving daily dosing of gentamicin and 245 receiving traditional dosing of gentamicin. Of the patients receiving daily gentamicin compared to traditional dosing, 95.7% (95% CI 94.9-96.6%) achieved the primary outcome versus 92% (95% CI 90.8 - 93.2%), 2.4% (95% CI 1.8-3%) developed endometritis versus 5.6% (4.5-6.7%), 1.6% (95% CI 1.1-2.1%) delivered neonates with sepsis versus 3.3% (CI 2.5-4.1%), and 36.9% required cesarean delivery versus 41.4%. In crude analysis, compared to traditional dosing, IDW daily dosing was associated with a lower risk of postpartum endometritis (RR 0.42, 95% CI 0.16-1.10, p = .032). After adjusting for BMI, diabetes mellitus, gestational blood pressure >140/90, group ß-Streptococcus status, race, advanced maternal age (>34 y), and parity, the IDW daily dosing group had a 5% greater chance of successful outcome (RR 1.05, 95% CI 1.00-1.10, p = .046) and a 64% lower risk of endometritis (RR 0.35, 95% CI 0.15-0.83, p = .017). Conclusion: Daily dosing of gentamicin using ideal body weight is associated with a lower risk of postpartum endometritis and high chance of a successful outcome in the treatment of intrapartum chorioamnionitis compared with traditional 8-hour dosing in our ethnically diverse, urban population and thus may be considered a superior option to every 8 hours dosing regimens.

Daily dosing of gentamicin using ideal body weight for the treatment of intrapartum chorioamnionitis: a pilot study.

PURPOSE: This study aimed to determine whether daily dosing of gentamicin using ideal body weight in the treatment of chorioamnionitis is effective. MATERIALS AND METHODS: We conducted a prospective observational study and followed all women receiving treatment for chorioamnionitis which included gentamicin daily dosing calculated using 5 mg/kg ideal body weight. Patients were excluded if pathological analysis of placenta did not confirm chorioamnionitis. Our primary outcome was resolution of infection following delivery without the development of maternal endometritis and/or neonatal sepsis. Ninety-five percent confidence intervals for proportions were calculated using exact binomial tests. These patients were retrospectively compared to patients who received treatment for chorioamnionitis which included traditional gentamicin every 8 h. RESULTS: The study included 160 patients. Of the patients receiving daily dosing (n = 80) compared to traditional dosing (n = 80), 96% (95% CI 95.7-97.6%) achieved the primary outcome versus 91% (88.9-93.1%), 2.5% (95% CI 1.2-3.8%) developed endometritis versus 6.3% (4.2-8.4%), 1.3% (95% CI 0.4-2.2%) delivered neonates with sepsis versus 2.5% (1.2-3.8%), and 39% required cesarean delivery (95% CI 46.2-53.8) versus 37% (33.2-40.8%). CONCLUSION: Daily dosing of gentamicin using ideal body weight is effective in successful treatment of chorioamnionitis without development endometritis and/or neonatal sepsis across different ethnicities.