Long-term effects of ciprofloxacin treatment on the gastrointestinal and oropharyngeal microbiome are more pronounced after longer antibiotic courses.

ABSTRACT

BACKGROUND: Urinary tract infections (UTIs) are one of the main reasons for antibiotic prescriptions in primary care. Recent studies demonstrate similar clinical outcomes with short vs. long antibiotics courses. The aim of this study was to investigate the differential collateral effect of ciprofloxacin treatment duration on the gastrointestinal and oropharyngeal microbiome in patients presenting with uncomplicated UTI to primary care practices in Switzerland, Belgium and Poland. METHODS: Stool and oropharyngeal samples were obtained from 36 treated patients and 14 controls at the beginning of antibiotic therapy, end of therapy and one month after the end of therapy. Samples underwent shotgun metagenomics. RESULTS: At the end of therapy, patients treated with both short (≤7 days) and long (>7 days) ciprofloxacin courses showed similar changes in the gastrointestinal microbiome compared to non-treated controls. After one month, most changes in patients receiving short courses were reversed; however, long courses led to increased abundance of the genera Roseburia, Faecalicatena and Escherichia. Changes in the oropharynx were minor and reversed to baseline levels within one month. Ciprofloxacin resistance encoding mutations in gyrA/B and parC/E reads were observed in both short and long treatment groups but decreased to baseline levels after one month. An increased abundance of resistance genes was observed in the gastrointestinal microbiome after longer treatment, and correlated to increased prevalence of aminoglycoside, ß-lactam, sulphonamide, and tetracycline resistance genes. CONCLUSION: Collateral effects on the gastrointestinal community, including an increased prevalence of antimicrobial resistance genes, persists for up to at least one month following longer ciprofloxacin therapy. These data support the use of shorter antimicrobial treatment duration.