Impact of Intrapartum Azithromycin on the Carriage and Antibiotic Resistance of Escherichia coli and Klebsiella pneumoniae in Mothers and their Newborns: a sub-study of a Randomized Double-Blind Trial Conducted in The Gambia and Burkina Faso

Clin Infect Dis. 2024 May 16:ciae280. doi: 10.1093/cid/ciae280. Online ahead of print.

Abstract

Background: Limited data exists on effects of intrapartum azithromycin on prevalence of carriage and antibiotic resistance of Enterobacterales.

Methods: We conducted a randomized trial in Gambia and Burkina Faso where women received intrapartum azithromycin (2g) or placebo. We determined impact of treatment on prevalence of carriage and antibiotic resistance of Escherichia coli and Klebsiella pneumoniae by analysing rectal swabs (RS), nasopharyngeal swabs (NPS), breast milk and recto-vaginal swabs (RVS). Bacteria were isolated microbiologically; antibiotic susceptibility was confirmed with an E-test. Prevalence ratios (PR) with 95% confidence intervals (CI's) were used for comparison between arms.

Results: In infants, E. coli carriage in RS was lower in the intervention than placebo arm at days 6 (63.0% vs. 75.2%, PR, 0.84; CI, 0.75-0.95) and 28 (52.7% vs. 70.4%, 0.75; 0.64-0.87) post-intervention. Prevalence of azithromycin-resistant E. coli was higher in the azithromycin arm at days 6 (13.4% vs. 3.6%, 3.75; 1.83-7.69) and 28 (16.4% vs. 9.6%, 1.71; 1.05-2.79). For K. pneumoniae, carriage in RS was higher in the intervention than placebo arm at days 6 (49.6% vs. 37.2%, 1.33; 1.08-1.64) and 28 (53.6% vs. 32.9%, 1.63; 1.31-2.03). Prevalence of azithromycin-resistant K. pneumoniae was higher in the azithromycin arm at day 28 (7.3% vs. 2.1%, 3.49; 1.30-9.37). No differences were observed for other sample types.

Conclusion: Intrapartum azithromycin decreased E. coli carriage but increased both K. pneumoniae carriage and azithromycin resistance in both bacteria. These data need to be considered together with efficacy results to balance the potential short- and long-term impact of the intervention.

Clinical trials registration: www.clinicaltrials.gov: NCT03199547.

Keywords: Escherichia coli; Klebsiella pneumoniae; Intrapartum azithromycin; antibiotic resistance; bacterial carriage.

Associated data

  • ClinicalTrials.gov/NCT03199547