Prophylactic azithromycin during labor increases S. aureus resistance in mothers and infants
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Key Takeaway
Consider that prophylactic azithromycin during labor increases S. aureus resistance in mothers and infants, though differences may not persist.
This is an RCT sub-study of the A-PLUS trial, involving 911 women and 915 liveborn infants at 8 sites in 7 countries. Women received prophylactic oral azithromycin during labor, and infants were followed accordingly.
The intervention was prophylactic oral azithromycin during labor, compared to placebo. The primary outcome was azithromycin resistance in nasal Staphylococcus aureus and Streptococcus pneumoniae.
In women, azithromycin resistance in S. aureus was higher and susceptibility lower in the azithromycin group versus placebo on day 7, 6 weeks, and 3 months after delivery (P < 0.001 for day 7 and 6 weeks; P = 0.009 for 3 months). In infants, resistance was higher and susceptibility lower 6 weeks after delivery in those born to women receiving azithromycin (P < 0.001). Resistance in S. pneumoniae was too sparse to interpret. Differences in resistance were no longer detected at 6 and 12 months post-partum in women and after 6 weeks through 12 months in infants.
Safety and tolerability were not reported. Key limitations include that azithromycin resistance in S. pneumoniae was too sparse to interpret, and follow-up was not fully aligned with the sample size hint of 1.4 months. Practice relevance was not reported, and results are based on p-values without confidence intervals or effect sizes.
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View Original Abstract ↓
BACKGROUND: Prophylactic oral azithromycin vs. placebo reduced maternal, but not neonatal, mortality/sepsis in the A-PLUS Randomized Trial. While prophylactic intrapartum azithromycin reduces maternal mortality/sepsis, it may promote antimicrobial resistance (AMR) in commensal bacteria,.
METHODS: Randomly selected women and their infants participating in A-PLUS were enrolled in a longitudinal cross-sectional sub-study to assess the presence of azithromycin resistance in selected bacteria in nasal cultures. Staphylococcus aureus and Streptococcus pneumoniae were cultured on selective agar, then azithromycin-containing agar to select for azithromycin resistant bacteria, identified biochemically. Azithromycin susceptibility was assessed by E-test. Nasal cultures were collected from women and infants between August 11, 2021 and September 18, 2023 during labor/day 1, day 7, 6 weeks, and 3, 6 and 12 months after delivery.
RESULTS: The study enrolled 911 women and 915 liveborn infants at 8 sites in 7 countries. Azithromycin resistance in S aureus was higher and azithromycin susceptibility was lower in women receiving azithromycin compared with those receiving placebo on day 7 (P < 0.001), 6 weeks (P < 0.001) and 3 months (P = 0.009) after delivery. Azithromycin resistance in S aureus was also higher and azithromycin susceptibility was lower 6 weeks after delivery (P < 0.001) in infants born to women receiving azithromycin, Azithromycin resistance in S. pneumoniae was too sparse to interpret.
CONCLUSIONS: There was an increase in prevalence of azithromycin resistance (or reduction in azithromycin susceptibility) in commensal nasal S. aureus between day 7, 6 weeks and 3 months in women exposed to azithromycin vs. placebo and only at 6 weeks in infants exposed to azithromycin vs. placebo. These differences between the azithromycin and placebo groups were no longer detected at 6 and 12 months post-partum in the women and after 6 weeks through 12 months in the infants.
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