Short-term increase in the carriage of azithromycin-resistant Escherichia coli and Klebsiella pneumoniae in mothers and their newborns following intra-partum azithromycin: a post hoc analysis of a double-blind randomized trial.

OBJECTIVES: To evaluate the impact of one oral dose of intrapartum azithromycin (2 g) on the carriage and antibiotic resistance of Escherichia coli and Klebsiella pneumoniae in the nasopharynx, breast milk and vaginal swabs of mothers and K. pneumoniae in the nasopharynx of their newborns. METHODS: We performed a post hoc analysis of a double-blind, placebo-controlled randomized-trial (ratio 1:1) conducted in The Gambia. Breast milk (BM) and vaginal swabs (VS) from mothers and nasopharyngeal swabs (NPS) from mother-newborn pairs were collected at different timepoints during the 4 week follow-up. Samples were processed using standard microbiological procedures. For BM and NPS post-intervention results were combined for analysis. RESULTS: In the original trial 829 mothers were randomized. In this analysis, complete sample sets were available for 630 mothers for E. coli analysis (76.0%) and 564 mother-newborn pairs for K. pneumoniae analysis (68.0%). For E. coli, carriage prevalence in BM and VS was similar in both arms but resistance was higher in the azithromycin arm in VS (2.6% versus 0%, P = 0.004). For K. pneumoniae, carriage prevalence was higher in the azithromycin arm for BM (13.8% versus 8.7%, P = 0.055) but not for VS or NPS. Prevalence of azithromycin resistant K. pneumoniae was higher in the azithromycin arm for BM (3.6% versus 1.0%, P = 0.050) and VS (1.5% versus 0% P = 0.057). CONCLUSIONS: Oral intrapartum azithromycin did not reduce carriage of E. coli and K. pneumoniae and was associated with an increase in the prevalence of azithromycin-resistant E. coli and K. pneumoniae isolates in BM and VS.

Long-term Impact of Oral Azithromycin Taken by Gambian Women During Labor on Prevalence and Antibiotic Susceptibility of Streptococcus pneumoniae and Staphylococcus aureus in Their Infants: Follow-up of a Randomized Clinical Trial.

Background: Oral azithromycin given to women in labor decreases maternal and neonatal bacterial carriage but increases azithromycin-resistant bacteria during at least 4 weeks following the intervention. We assessed the prevalence of bacterial carriage and azithromycin resistance 12 months after treatment among study infants. Methods: Nasopharyngeal swabs (NPSs) were collected between November 2014 and May 2015 from children aged 11-13 months whose mothers had received azithromycin or placebo during labor. Streptococcus pneumoniae and Staphylococcus aureus were isolated using conventional microbiological methods. Antibiotic susceptibility was determined by disk diffusion and confirmed by Etest or VITEK-2. Results: NPSs were collected from 461 children. The prevalence of S. pneumoniae and S. aureus was similar between children from the azithromycin and placebo arms (85.0% vs 82.1%; odds ratio [OR], 1.23 [95% confidence interval {CI}, .73-2.08] for S. pneumoniae and 21.7% vs 21.3%; OR, 1.02 [95% CI, .64-1.64] for S. aureus). Prevalence of azithromycin-resistant S. pneumoniae was similar in both arms (1.8% vs 0.9% in children from the azithromycin and placebo arms, respectively; OR, 2.10 [95% CI, .30-23.38]); resistance to other antibiotics was also similar between arms. For S. aureus, there was no difference in azithromycin resistance between children in the azithromycin (3.1%) and placebo (2.6%) arms (OR, 1.22 [95% CI, .35-4.47]) or resistance to any other antibiotics. Conclusions: The higher prevalence of S. aureus azithromycin resistance observed among women treated during labor and their babies 4 weeks after treatment had waned 12 months after delivery. Azithromycin intervention did not induce other antibiotic resistance to S. pneumoniae or S. aureus. Clinical Trials Registration: NCT01800942.