Effectiveness of intrapartum azithromycin to prevent infections in planned vaginal births in low-income and middle-income countries: a post-hoc analysis of data from a multicentre, randomised, double-blind, placebo-controlled trial

Carlo, Waldemar A; Tita, Alan T N; Moore, Janet L; Mwenechanya, Musaku; Chomba, Elwyn; Hemingway-Foday, Jennifer J; Kavi, Avinash; Metgud, Mrityunjay C; Goudar, Shivaprasad S; Derman, Richard J; A-PLUS Trial Group

Citation:

Carlo WA, Tita ATN, Moore JL, Mwenechanya M, Chomba E, Hemingway-Foday JJ, Kavi A, Metgud MC, Goudar SS, Derman RJ, Group A-PLUST. Effectiveness of intrapartum azithromycin to prevent infections in planned vaginal births in low-income and middle-income countries: a post-hoc analysis of data from a multicentre, randomised, double-blind, placebo-controlled trial. The Lancet Global Health 2025;13:e689–e697.

Abstract:

BACKGROUND: In 2023, the Azithromycin Prevention in Labor Use (A-PLUS) trial showed intrapartum azithromycin reduces maternal sepsis or death in women with planned vaginal delivery in low-resource settings, but whether it reduces maternal infection is unknown. We aimed to evaluate the effectiveness of intrapartum azithromycin in reducing maternal infection. METHODS: We performed a post-hoc analysis of the multicentre, facility-based, randomised, double-blind, placebo-controlled A-PLUS trial. This trial compared prophylactic intrapartum single oral dose of 2 g azithromycin versus placebo on maternal morbidity and mortality in low-resource settings in southeast Asia and Africa from Sept 9, 2020, to Aug 18, 2022. The trial enrolled women in labour at 28 weeks' gestation (or later) at eight sites in the Democratic Republic of the Congo, Kenya, Zambia, Bangladesh, India, Pakistan, and Guatemala and found that azithromycin reduced the incidence of maternal sepsis or death. The primary outcome of the present analysis was the incidence of any maternal infection in the azithromycin versus placebo groups, which was defined as one or more of these infections after randomisation: chorioamnionitis, endometritis, perineal or caesarean wound infection, abdominopelvic abscess, mastitis or breast abscess, and other infections. Any neonatal infection was also analysed. All analyses were by intention to treat in all those with data available for that outcome. Relative risks (RRs) and 95% CIs were estimated with a Poisson model adjusted for treatment group and site. Subgroup analyses included a two-way interaction test between intervention group and subgroup. A-PLUS was registered at ClinicalTrials.gov, number NCT03871491. FINDINGS: 29 278 women were randomly assigned to groups: 14 590 to receive azithromycin, 14 688 to receive placebo. Baseline characteristics were similar between the azithromycin and placebo groups (43·3% vs 43·4% primiparous, 8·5% vs 8·7% high risk for infection). The presence of any maternal infection occurred less often in the azithromycin group (580 [4·0%] of 14 558) compared with the placebo group (824 [5·6%] of 14 661 women; RR 0·71, 95% CI 0·64-0·79, p<0·0001). Any neonatal infection did not differ between treatment groups. Adverse events were not detected. INTERPRETATION: Among women planning vaginal delivery, this analysis provides evidence indicating that intrapartum azithromycin is associated with a lower incidence of maternal infections than placebo. FUNDING: The Eunice Kennedy Shriver National Institute of Child Health and Human Development and Bill and Melinda Gates Foundation via Foundation of National Institutes of Health. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

Carlo WA, Tita ATN, Moore JL, Mwenechanya M, Chomba E, Hemingway-Foday JJ, Kavi A, Metgud MC, Goudar SS, Derman RJ, Lokangaka A, Tshefu A, Bauserman M, Patterson JK, Shivkumar P, Waikar M, Patel A, Hibberd PL, Nyongesa P, Esamai F, Ekhaguere OA, Bucher S, Jessani S, Tikmani SS, Saleem S, Goldenberg RL, Billah SM, Lennox R, Haque R, Petri W, Mazariegos M, Krebs NF, Babineau DC, McClure EM, Koso-Thomas M, Mweemba T, Banda E, Chimfwembe M, Nakazwe R, Collins M, Leal S, Subramaniam A, Lal CV, Parepalli S, Aceituno A, Kim J, Jackson K, Williams A, Trotta M, Miodovnik M, Wallace J, Lomendje G, Kalonji M, Junior M, Patterson J, Takoy P, Gado J, Bossenya J, Kalombo E, Kombi C, Manrique M, Westcott J, Siraj S, Sadeq-ur-Rahman W, Singh L, Farzana A, Jahan F, Maliha ZT, Kairy R, Chisolm C, Sinkin RA, Somannavar MS, Beniwadi K, Harkuni SU, Ganarchari MS, Hundekar UR, Patil A, Bharamashetti A, Alur N, Nyamagoud S, Kajagar C, Dhaded SM, Mallapur AA, Pol R, Katageri GM, Ramadurg UY, Yelamali BC, Bhurle A, Bidri SR, Mathapati SS, Patil MM, Patil PG, Bijapure HR, Doddihal CR, Gudadinni MR, Bagali SO, Jaeger F, Naqvi F, Ghanchi NK, Habib Z, Ahmed I, Roujani S, Naqvi S, Reza S, Yasmin H, Khan M, Shaikh M, Bozdar H, Dad P, Kurhe KG, Khedikar V, Gedam C, Bhargav S, Sadaf S, Shrivastava D, Gaidhane A, Jungari M, Jain M, Nasre M, Shrikhande S, Deotale V, Liechty EA, Sagwe A, Otieno K, Kemboi M, Misati A, Kigen G. Effectiveness of intrapartum azithromycin to prevent infections in planned vaginal births in low-income and middle-income countries: a post-hoc analysis of data from a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Glob. Health 2025;13:e689–e697.Abstract

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.)

Nguata M, Orwa J, Kigen G, Kamaru E, Emonyi W, Kariuki S, Newton C, Ongeri L, Mwende R, Gichuru S, Atwoli L. Association between psychosis and substance use in Kenya. Findings from the NeuroGAP-Psychosis study. Frontiers in PsychiatryFrontiers in Psychiatry 2024;15:1301976.Abstract

Background: Substance use is prevalent among people with mental health issues, and patients with psychosis are more likely to use and misuse substances than the general population. Despite extensive research on substance abuse among the general public in Kenya, there is a scarcity of data comparing substance use among people with and without psychosis. This study investigates the association between psychosis and various substances in Kenya.Methods: This study utilized data from the Neuro-GAP Psychosis Case-Control Study between April 2018 and December 2022. The KEMRI-Wellcome Trust Research Programme recruited participants from various sites in Kenya, including Kilifi County, Malindi Sub-County, Port Reitz and Coast General Provincial Hospitals, and Moi Teaching and Referral Hospital, as well as affiliated sites in Webuye, Kapenguria, Kitale, Kapsabet, and Iten Kakamega. The collected data included sociodemographic information, substance use, and clinical diagnosis. We used the summary measures of frequency (percentages) and median (interquartile range) to describe the categorical and continuous data, respectively. We examined the association between categorical variables related to psychosis using the chi-square test. Logistic regression models were used to assess the factors associated with the odds of substance use, considering all relevant sociodemographic variables.Results: We assessed a total of 4,415 cases and 3,940 controls. Except for alcohol consumption (p-value=0.41), all forms of substance use showed statistically significant differences between the case and control groups. Cases had 16% higher odds of using any substance than controls (aOR: 1.16, 95%CI: 1.05-1.28, p=0.005). Moreover, males were 3.95 times more likely to use any substance than females (aOR:3.95; 95%CI: 3.43-4.56). All the categories of living arrangements were protective against substance use.Conclusion: The findings of this study suggest that psychotic illnesses are associated with an increased likelihood of using various substances. These findings are consistent with those of previous studies; however, it is crucial to investigate further the potential for reverse causality between psychosis and substance abuse using genetically informed methods.

Moki C, Kigen G, Busakhala N. Effectiveness and Nephrotoxicity of Polymyxin B among Intensive Care Unit Patients: A Clinical Evaluation. African Journal of Pharmacy and Alternative Medicine 2024;3:85-92.Abstract

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.

Gabriel Kigen

Associate Professor of Pharmacology & Therapeutics

Effectiveness of intrapartum azithromycin to prevent infections in planned vaginal births in low-income and middle-income countries: a post-hoc analysis of data from a multicentre, randomised, double-blind, placebo-controlled trial

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