Context-specific impact of antimicrobial stewardship on antibiotic use and antibiotic resistance in hospitals in a lower-middle income country - results from an implementation study with a controlled interrupted time series design in Vietnam

Introduction: High-quality evidence regarding the impact of antimicrobial stewardship (AMS) is limited in Asia. In this study, we aimed to determine the effects of a pharmacist-led prospective audit with feedback intervention, as part of an AMS programme following national guidelines, in two provincial-level general hospitals in Vietnam, a lower-middle-income country. Methods: We performed controlled interrupted time-series analyses to evaluate the impact of an AMS intervention on antibiotic use in days of therapy per 1000 patient-days, antibiotic non-susceptibility percentage and patient outcomes. In each hospital, four wards received the intervention and four wards acted as controls. Pre-intervention periods began in January 2019 and continued to May 2020 (Hospital 1) and July 2020 (Hospital 2), followed by a 12-month post-intervention period. Results: In Hospital 1, the intervention was associated with a reduction in the level of antibiotic use (95.9, 95% CI 10.9, 180.8), although there was no evidence for a change in trend (0.9-3.6, 5.4). In contrast, in Hospital 2, there was no evidence for a change in either level (6.3-83.7, 96.3) or trend (-2.1-4.8, 0.6). In Hospital 1, we observed a decreasing trend in antibiotic non-susceptibility among hospital-acquired Escherichia coli to aminoglycosides (odds ratio: 0.870.78, 0.97), but increasing for Pseudomonas aeruginosa to carbapenems (1.111.00, 1.22) and Acinetobacter spp. to aminoglycosides (1.071.00, 1.27). In Hospital 2, evidence indicated decreasing trends in Acinetobacter spp. to carbapenems (0.960.88, 1.00), ciprofloxacin (0.930.85, 1.00), and piperacillin-tazobactam (0.940.78, 1.00), but increasing for P. aeruginosa to aminoglycosides (1.071.00, 1.20, ciprofloxacin (1.451.18, 1.77), and ceftazidime (1.031.00, 1.19). We did not find evidence that the intervention was associated with changes in mortality or hospitalisation costs. Conclusion: The impact of AMS varied between the two hospitals, highlighting context-specific implementation challenges and the necessity to monitor changes in antibiotic resistance over time to tailor interventions that respond to local resistance epidemiology.