Trimethoprim prescription and subsequent resistance in childhood urinary infection: Multilevel modelling analysis

Background Antibiotic resistance is a growing concern and antibiotic usage the main contributing factor, but there are few studies examining antibiotic use and resistance in children. Aim To investigate the association between previous trimethoprim prescribing and resistance in urinary Escherichia coli (E. coli) isolates in children. Design and setting Retrospective, population cohort study in Tayside, Scotland. Method Multilevel modelling of linked microbiology and dispensed prescribing data for 1373 =16-yearolds with E. coli urinary isolates in 2004-2009, examining the association between prior trimethoprim prescription and subsequent trimethoprim resistance in people with urinary E. coli isolates. Results Trimethoprim resistance was common (26.6%, 95% confidence interval [CI] = 24.6 to 28.6). Previous trimethoprim prescription was associated with subsequent culture of trimethoprim-resistant E. coli, with more recent prescription being more strongly associated with resistance. After adjusting for the number of previous E. coli isolates and sample year, trimethoprim prescribing in the previous 84 days remained significantly associated with culturing trimethoprim-resistant E. coli (adjusted OR 4.71, 95% CI = 1.83 to 12.16 for the previous 15-28 days versus never prescribed; adjusted OR 3.16, 95% CI = 1.63 to 6.13 for the previous 29-84 days); however, associations were not statistically significant for longer periods since prior exposure. Conclusion Trimethoprim prescription has implications for future resistance in individual children, as well as at population level. Clinicians must ensure appropriateness of treatment choice and duration, and alternative antibiotics should be considered for childhood urinary tract infections if trimethoprim has been prescribed in the preceding 3 months.