Optimizing antibiotic use in Indonesia: A systematic review and evidence synthesis to inform opportunities for intervention.

Background: A major driver of antimicrobial resistance (AMR) and poor clinical outcomes is suboptimal antibiotic use, although data are lacking in low-resource settings. We reviewed studies on systemic antibiotic use (WHO ATC/DDD category J01) for human health in Indonesia, and synthesized available evidence to identify opportunities for intervention. Methods: We systematically searched five international and national databases for eligible peer-reviewed articles, in English and Indonesian, published between 1 January 2000 and 1 June 2021 including: (1) antibiotic consumption; (2) prescribing appropriateness; (3) antimicrobial stewardship (AMS); (4) consumers' and providers' perceptions. Two independent reviewers included studies and extracted data. Study-level data were summarized using random-effects model meta-analysis for consumption and prescribing appropriateness, effect direction analysis for antimicrobial stewardship (AMS) interventions, and qualitative synthesis for perception surveys. (PROSPERO: CRD42019134641). Findings: Of 9323 search hits, we included 100 reports on antibiotic consumption (20), prescribing appropriateness (49), AMS interventions (13), and/or perception (25) (8 categorized in >1 domain). The pooled estimate of overall antibiotic consumption was 134.8 DDD per 100 bed-days (95%CI 82.5-187.0) for inpatients and 121.1 DDD per 1000 inhabitants per day (10.4-231.8) for outpatients. Ceftriaxone, levofloxacin, and ampicillin were the most consumed antibiotics in inpatients, and amoxicillin, ciprofloxacin, and cefadroxil in outpatients. Pooled estimates for overall appropriate prescribing (according to Gyssens method) were 33.5% (18.1-53.4) in hospitals and 49.4% (23.7-75.4) in primary care. Pooled estimates for appropriate prescribing (according to reference guidelines) were, in hospitals, 99.7% (97.4-100) for indication, 84.9% (38.5-98.0) for drug choice, and 6.1% (0.2-63.2) for overall appropriateness, and, in primary care, 98.9% (60.9-100) for indication, 82.6% (50.5-95.7) for drug choice and 10.5% (0.8-62.6) for overall appropriateness. Studies to date evaluating bundled AMS interventions, although sparse and heterogeneous, suggested favourable effects on antibiotic consumption, prescribing appropriateness, guideline compliance, and patient outcomes. Key themes identified in perception surveys were lack of community antibiotic knowledge, and common non-prescription antibiotic self-medication. Interpretation: Context-specific intervention strategies are urgently needed to improve appropriate antibiotic use in Indonesian hospitals and communities, with critical evidence gaps concerning the private and informal healthcare sectors. Funding: Wellcome Africa Asia Programme Vietnam.