Department of Obstetrics & Gynecology, St. John's Episcopal Hospital, Far Rockaway, NY, United States of America.
Department of Biomedical and Health Informatics, Rutgers University School of Health Professions, Newark, NJ, United States of America.
PLoS One. 2020 Dec 21;15(12):e0244266. doi: 10.1371/journal.pone.0244266. eCollection 2020.
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.
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.
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.
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.
本研究旨在评估与不使用大环内酯类药物相比，在 COVID-19 大流行期间阿奇霉素短缺的情况下，克拉霉素作为择期剖宫产术辅助抗生素预防的安全性和有效性。
我们进行了一项多中心、前瞻性观察性队列研究，时间为 2020 年 3 月 23 日至 2020 年 6 月 1 日。我们随访了所有接受克拉霉素或非大环内酯类抗生素辅助择期剖宫产术预防手术的患者。主要结局是产后子宫内膜炎的发生。次要结局包括剖宫产时羊水胎粪污染、新生儿败血症、新生儿重症监护病房（NICU）入院和新生儿急性呼吸窘迫综合征（ARDS）。所有患者均接受了 SARS-CoV-2 感染检测，结果均为阴性。
本研究共纳入 240 例患者，其中 133 例患者接受克拉霉素治疗，107 例患者接受非辅助性大环内酯类预防治疗。与未接受辅助预防治疗的患者相比，接受克拉霉素治疗的患者产后子宫内膜炎发生率显著降低（4.5%比 11.2%，p=0.025）。在未调整（未校正）分析中，克拉霉素组发生子宫内膜炎的风险显著低于对照组（66%的风险降低，95%CI 0.12 至 0.95，p=0.040）。当调整了感知混杂因素后，再次发现显著差异（67%的风险降低，95%CI 0.11 至 0.97，p=0.034）。对包括黑人种族、BMI 和年龄在内的显著不同的人口统计学因素进行了分层分析。在未校正和校正模型中，与未接受辅助性大环内酯类药物治疗的患者相比，黑人种族女性接受克拉霉素治疗后发生子宫内膜炎的风险显著降低（未校正：87%的风险降低，95%CI 0.08 至 0.83，p=0.032；校正：91%的风险降低，95%CI 0.06 至 0.79，p=0.026）。在 18-29 岁的女性中也观察到了同样的结果（未校正模型：79%的风险降低，95%CI 0.06 至 0.80，p=0.014；校正模型：75%的风险降低，95%CI 0.06 至 0.94，p=0.028）。所有其他分层分析均未显示子宫内膜炎风险的显著差异。
本研究表明，在 COVID-19 大流行期间，克拉霉素用于择期剖宫产术辅助手术预防可能是一种安全的选择，在阿奇霉素无法获得的情况下，可能为子宫内膜炎提供适当的预防，尤其是对于黑人种族女性和 18-29 岁的女性。
