Department of Pharmacology & Toxicology, Moi University School of Medicine
Eldoret, Kenya
Background: The use of azithromycin reduces maternal infection in women during unplanned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death.
Methods: In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks' gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo. The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for maternal benefit.
Results: A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P = 0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events.
Conclusions: Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; A-PLUS ClinicalTrials.gov number, NCT03871491.)
Polymyxin B is a reserve antibiotic, but there has been an upsurge in its use due to a rise in multidrug-resistant gram-negative bacteria. However, nephrotoxicity and resistance concerns persist, with global resistance rates reaching 29%. Effectiveness of Polymyxin B (clinical and microbiological response) and the frequency of nephrotoxicity is not well documented in resource limited settings. Research is essential to guide optimization of Polymyxin B therapy and inform the adoption of measures for early detection of kidney injury to prevent damage. This study aimed to assess the effectiveness of Polymyxin B by evaluating clinical and microbiological responses and determining nephrotoxicity incidence using KDIGO criteria in ICU patients at Moi Teaching and Referral Hospital (MTRH). A prospective observational cohort study was conducted at MTRH ICUs between December 2021 and November 2022, on patients treated with Polymyxin B. Data on demographics, comorbidities, Polymyxin B dosage regimens, clinical responses, and microbiological results were collected. Descriptive statistics summarized patient characteristics, while associations between dosage regimens and outcomes were evaluated using Fisher's exact test and multivariate regression, with a p<0.05 considered statistically significant. Forty-four patients with a mean age of 48 years were included; 66% were male, and cerebrovascular disease was the most common comorbidity. All patients had multidrug-resistant gram-negative infections qualifying for Polymyxin B therapy. Most (89%) received monotherapy, with 86% achieving a good clinical response, 7% experiencing treatment failure, and 7% dying. Doses of 20,000–25,000 IU/Kg/day were associated with microbiological eradication and good clinical response (p<0.001), while 15,000 IU/Kg/day was associated with treatment failure. Acute kidney injury occurred in 48% of patients, with 68% developing hypomagnesemia. Polymyxin B at doses of between 20,000-25,000IU/Kg/day should be considered as a starting dose due to the association with good clinical response, with alternate-day monitoring of serum creatinine levels for early detection of nephrotoxicity.