Class-matched antibiotic dispensing and susceptibility transitions in recurrent urinary gram-negative bacilli

Antimicrobial resistance (AMR) among urinary Gram-negative bacilli (GNB) is rising in Saudi Arabia, but how interim antibiotic exposure relates to within-patient changes in susceptibility is not well characterized. We evaluated the association between class-matched antibiotic exposure occurring between consecutive cultures and susceptible (S)-to-non-susceptible (NS) and non-susceptible-to-susceptible transitions.

In a single-center, retrospective, culture-based, pharmacy-linked paired-culture cohort at a 500-bed tertiary hospital in southern Saudi Arabia (Aseer Central Hospital [ACH]), consecutive same-patient, same-species urinary GNB cultures 14-365 days apart formed pairs, and interim exposure was defined as ACH-recorded antibiotic dispensing. For each of the seven feasible phenotypes, adjusted transition models estimated S→NS odds and separate direct models estimated NS→S odds, with supporting analyses using inverse probability weighting, cross-class models, E-values, penalized-likelihood sensitivity analyses, and exploratory pragmatic null-covariable diagnostics.

The primary cohort comprised 1,274 pairs from 1,078 patients, of whom 807 (74.9%) had at least one interim ACH-recorded systemic antibiotic dispensing. Class-matched dispensing was associated with higher adjusted odds of an S→NS transition for extended-spectrum cephalosporins (OR, 3.83), difficult-to-treat resistance (OR, 2.91), piperacillin-tazobactam (OR, 2.46), and fluoroquinolones (OR, 2.29), but not carbapenems (OR, 0.93). In direct models, matched dispensing was associated with lower odds of an NS→S transition, reaching significance only for piperacillin-tazobactam (OR, 0.39).

In recurrent urinary GNB, interim class-matched hospital-recorded antibiotic dispensing was associated with within-patient S→NS transitions for several clinically important phenotypes. These observational associations do not establish treatment effects; they identify patterns for confirmation in prospective studies and may inform surveillance and stewardship evaluation.