A sub-study of a randomized trial conducted in two African countries found that azithromycin administration during childbirth reduced Escherichia coli prevalence in infants but increased Klebsiella pneumoniae carriage and azithromycin resistance in both bacteria, researchers reported yesterday in Clinical Infectious Diseases.
The phase 3 PregnAnZI-2 trial recruited and randomized 12,000 women in Gambia and Burkina Faso to received either oral azithromycin or placebo during labor. Although that trial found that intrapartum azithromycin did not achieve the primary outcome of reducing neonatal sepsis and mortality, it did reduce neonatal and maternal infections.
In the sub-study, investigators analyzed breast milk and rectal, recto-vaginal, and nasopharyngeal swab samples from 500 mother-infant pairs recruited for the trial to determine the impact of intrapartum azithromycin on the prevalence of carriage and antibiotic resistance of E coli and K pneumoniae.
Impact observed in infants
While little impact was found on the samples collected from the mothers, E coli carriage in infant rectal samples was lower in the intervention than placebo arm at days 6 (63.0% vs 75.2%; prevalence ratio [PR], 0.84; 95% confidence interval [CI], 0.75 to 0.95) and 28 (52.7% vs 70.4%; PR, 0.75; 95% CI, 0.64 to 0.87) postintervention. But the prevalence of azithromycin-resistant E coli was higher in the azithromycin arm at days 6 (13.4% vs 3.6%; PR, 3.75; 95% CI, 1.83 to 7.69) and 28 (16.4% vs 9.6%; PR, 1.71; 95% CI, 1.05 to 2.79).
For K pneumoniae, carriage in infant rectal samples was higher in the intervention than placebo arm at days 6 (49.6% vs 37.2%; PR, 1.33; 95% CI, 1.08 to 1.64) and 28 (53.6% vs 32.9%; PR, 1.63; 95% CI, 1.31 to 2.03), and the prevalence of azithromycin-resistant K pneumoniae was higher in the azithromycin arm at day 28 (7.3% vs 2.1%; PR, 3.49; 95% CI, 1.30 to 9.37).
The investigators say increased carriage of azithromycin-resistant E coli and K pneumoniae could contribute to the spread of azithromycin resistance in the community.
"These results need to be considered when evaluating the overall impact of the use of azithromycin to prevent maternal, neonatal, or infant infections," they wrote.