Baseline azithromycin resistance in the gut microbiota of preterm born infants

• Published in: Pediatric research 2024-01, Vol.95 (1), p.205-212
• Main Authors: Gallacher, David J., Zhang, Lei, Aboklaish, Ali F., Mitchell, Emma, Wach, Richard, Marchesi, Julian R., Kotecha, Sailesh
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Azithromycin - pharmacology; Azithromycin - therapeutic use; Bacteria; Clinical; Clinical outcomes; Clinical Research Article; Drug resistance; Drug Resistance, Bacterial - genetics; Gastrointestinal Microbiome; Humans; Infant; Infant, Newborn; Infant, Premature; Macrolides - pharmacology; Macrolides - therapeutic use; Medicine; Medicine & Public Health; Microbial Sensitivity Tests; Microbiota; Newborn babies; Pediatric Surgery; Pediatrics; Polymerase chain reaction; Premature babies; Quantitative analysis
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1038/s41390-023-02743-7

Background Macrolides, including azithromycin, are increasingly used in preterm-born infants to treat Ureaplasma infections. The baseline carriage of macrolide resistance genes in the preterm stool microbiota is unknown. Objectives Identify carriage of azithromycin resistant bacteria and the incidence of macrolide resistant genes. Methods Azithromycin resistant bacteria were isolated from serial stool samples obtained from preterm infants (≤32 weeks’ gestation) by culturing aerobically/anaerobically, in the presence/absence of azithromycin. Using quantitative PCR, we targeted 6 common macrolide resistance genes ( erm(A) , erm(B) , erm(C) , erm(F) , mef(A/E), msr(A) ) in DNA extracted from selected bacteria resistant to azithromycin. Results From 89 stool samples from 37 preterm-born infants, 93.3% showed bacterial growth in aerobic or anaerobic conditions. From the 280 azithromycin resistant isolates that were identified, Staphylococcus (75%) and Enterococcus (15%) species dominated. Macrolide resistance genes were identified in 91% of resistant isolates: commonest were erm(C) (46% of isolates) and msr(A) (40%). Multiple macrolide resistance genes were identified in 18% of isolates. Conclusion Macrolide resistance is common in the gut microbiota of preterm-born infants early in life, most likely acquired from exposure to the maternal microbiota. It will be important to assess modulation of macrolide resistance, if macrolide treatment becomes routine in the management of preterm infants. Impact Statement Azithromycin resistance is present in the stool microbiota in the first month of life in preterm infants 91% of azithromycin resistant bacteria carried at least one of 6 common macrolide resistant genes Increasing use of macrolides in the preterm population makes this an important area of study