Optimizing antibiotic use in Indonesia: a systematic review and synthesis of current evidence to inform opportunities for intervention
Authors: Limato Ralalicia , Lazarus Gilbert , Dernison Puck , Mudia Manzilina , Alamanda Monik , Nelwan Erni J. , Sinto Robert , Karuniawati Anis , van Doorn H. Rogier , Hamers Raph L. 
Published: February 2022

ABSTRACTIntroductionA 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.MethodsWe 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) perceptions among consumers and providers. 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 AMS interventions, and qualitative synthesis for perception surveys. (PROSPERO CRD42019134641)ResultsOf 9323 search hits, we included 100 reports on antibiotic consumption (20), prescribing appropriateness (49), AMS (13), and/or perception (25) (8 categorized in >1 domain). The pooled estimate of overall antibiotic consumption was 110.1 DDD/100 patient-days (95%CI98.5-121.6), with ceftriaxone, ampicillin and levofloxacin being most consumed. Pooled estimates for overall appropriate prescribing (according to Gyssens method) were 33.5% (95%CI18.1-53.4%) in hospitals and 49.4% (95%CI23.7-75.4%) in primary care. Pooled estimates for appropriate prescribing (according to reference guidelines) were, in hospitals, 99.7% (95%CI97.4-100%) for indication, 84.9% (95%CI38.5-98.0%) for drug choice, and 6.1% (95%CI0.2-63.2%) for overall appropriateness, and, in primary care, 98.9% (95%CI60.9-100%) for indication, 82.6% (95%CI50.5%-95.7%) for drug choice and 10.5% (95%CI0.8-62.6%) for overall appropriateness. The few AMS intervention studies conducted to date suggested potential to reduce antibiotic consumption and improve prescribing appropriateness. Key themes identified in perception surveys were lack of antibiotic knowledge among consumers and non-prescription antibiotic self-medication.ConclusionsContext-specific strategies are urgently needed to improve rational antibiotic use in Indonesian hospitals and communities, with critical evidence gaps concerning private and informal health providers.KEY QUESTIONSWhat is already known?•Indonesia is a potential AMR hotspot, where, based on pharmaceutical sales data, antibiotic consumption increased 2.5-fold between 2000 and 2015, mostly driven by broad-spectrum penicillins, fluoroquinolones and cephalosporins.•Representative contemporary data on antibiotic use are lacking, although anecdotal data suggest antibiotic overuse in the healthcare system, widespread over-the-counter use in communities, and high rates of AMR mostly among common Gram-negative bacteria.•A comprehensive review on antibiotic use in human health in Indonesia has not been conducted to date.What are the new findings?•Available data spanning the past 20 years, suggested that only 34% and 49% of antibiotics were appropriately prescribed in hospital and primary care settings, respectively, although the quality of the evidence was low.•Publications evaluating AMS interventions have been sparse to date, demonstrating the need to strengthen the local research base to develop context-specific and sustainable AMS models.•Community surveys suggested important gaps in antibiotic knowledge, and that non-prescription antibiotic self-medication is common practice, although data to quantify this problem and its drivers are lacking.What do the new findings imply?•Available evidence synthesised in this Review provides important insights in the magnitude and patterns of antibiotic use, and associated patient and health system factors, which helps define opportunities for optimising responsible antibiotic use.•Critical evidence gaps exist on informal and formal private health care providers, geographic areas outside of Java Island, as well as effective AMS models that consider country-specific socio-cultural, economic and political circumstances.•Optimization of antimicrobial use as a means to tackle AMR should be a priority of the national agenda for universal health coverage.