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

IntroductionHigh-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. MethodsWe 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. ResultsIn 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: 0.87[0.78, 0.97]), but increasing for Pseudomonas aeruginosa to carbapenems (1.11[1.00, 1.22]) and Acinetobacter spp. to aminoglycosides (1.07[1.00, 1.27]). In Hospital 2, evidence indicated decreasing trends in Acinetobacter spp. to carbapenems (0.96[0.88, 1.00]), ciprofloxacin (0.93[0.85, 1.00]), and piperacillin-tazobactam (0.94[0.78, 1.00]), but increasing for P. aeruginosa to aminoglycosides (1.07[1.00, 1.20], ciprofloxacin (1.45[1.18, 1.77]), and ceftazidime (1.03[1.00, 1.19]). We did not find evidence that the intervention was associated with changes in mortality or hospitalisation costs. ConclusionThe 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. WHAT IS ALREADY KNOWN ON THIS TOPICO_LIPrevious systematic reviews and recent interrupted time series (ITS) studies have shown large variations in the impact of antimicrobial stewardship (AMS) on hospital antibiotic use and resistance. Few previous ITS studies of AMS have used a control in their analysis. C_LI WHAT THIS STUDY ADDSO_LIUsing a strong quasi-experimental study design with a control group, we generated empirical evidence on the multi-faceted effects of an AMS intervention on antibiotic use and resistance in hospitals in a middle-income country in Asia. C_LIO_LIThe implementation of prospective audit and feedback in the context of established AMS programmes following the national guidelines had different effects on total antibiotic use and antibiotic non-susceptibility proportions among common hospital-acquired pathogens found in Vietnam. C_LI HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYO_LIThis study contributes evidence from a strong study design on the effects of AMS implementation in hospitals in a middle-income country in Asia, which can inform future AMS programmes in similar settings. C_LIO_LIIt highlights the need to monitor the emergence and spread of antibiotic resistance in hospital settings in Asia to support development and design of novel interventions for AMS and other programmes to respond to the fast-changing resistance profiles of bacterial pathogens in hospitals. C_LI