SummaryBackgroundIn southeast Asia, antibiotic prescription in febrile patients attending primary care is common, and a probable contributor to the high burden of antimicrobial resistance. The objective of this trial was to explore whether C-reactive protein (CRP) testing at point of care could rationalise antibiotic prescription in primary care, comparing two proposed thresholds to classify CRP concentrations as low or high to guide antibiotic treatment.MethodsWe did a multicentre, open-label, randomised, controlled trial in participants aged at least 1 year with a documented fever or a chief complaint of fever (regardless of previous antibiotic intake and comorbidities other than malignancies) recruited from six public primary care units in Thailand and three primary care clinics and one outpatient department in Myanmar. Individuals were randomly assigned using a computer-based randomisation system at a ratio of 1:1:1 to either the control group or one of two CRP testing groups, which used thresholds of 20 mg/L (group A) or 40 mg/L CRP (group B) to guide antibiotic prescription. Health-care providers were masked to allocation between the two intervention groups but not to the control group. The primary outcome was the prescription of any antibiotic from day 0 to day 5 and the proportion of patients who were prescribed an antibiotic when CRP concentrations were above and below the 20 mg/L or 40 mg/L thresholds. The primary outcome was analysed in the intention-to-treat and per-protocol populations. The trial is registered with ClinicalTrials.gov, number NCT02758821, and is now completed.FindingsBetween June 8, 2016, and Aug 25, 2017, we recruited 2410 patients, of whom 803 patients were randomly assigned to CRP group A, 800 to CRP group B, and 807 to the control group. 598 patients in CRP group A, 593 in CRP group B, and 767 in the control group had follow-up data for both day 5 and day 14 and had been prescribed antibiotics (or not) in accordance with test results (per-protocol population). During the trial, 318 (39%) of 807 patients in the control group were prescribed an antibiotic by day 5, compared with 290 (36%) of 803 patients in CRP group A and 275 (34%) of 800 in CRP group B. The adjusted odds ratio (aOR) of 0·80 (95% CI 0·65–0·98) and risk difference of −5·0 percentage points (95% CI −9·7 to −0·3) between group B and the control group were significant, although lower than anticipated, whereas the reduction in prescribing in group A compared with the control group was not significant (aOR 0·86 [0·70–1·06]; risk difference −3·3 percentage points [–8·0 to 1·4]). Patients with high CRP concentrations in both intervention groups were more likely to be prescribed an antibiotic than in the control group (CRP ≥20 mg/L: group A vs control group, p<0·0001; CRP ≥40 mg/L: group B vs control group, p<0·0001), and those with low CRP concentrations were more likely to have an antibiotic withheld (CRP <20 mg/L: group A vs control group, p<0·0001; CRP <40 mg/L: group B vs control group, p<0·0001). 24 serious adverse eve...

IntroductionLow-income and middle-income countries (LMICs) are crucial in the global response to antimicrobial resistance (AMR), but diverse health systems, healthcare practices and cultural conceptions of medicine can complicate global education and awareness-raising campaigns. Social research can help understand LMIC contexts but remains under-represented in AMR research.ObjectiveTo (1) Describe antibiotic-related knowledge, attitudes and practices of the general population in two LMICs. (2) Assess the role of antibiotic-related knowledge and attitudes on antibiotic access from different types of healthcare providers.DesignObservational study: cross-sectional rural health behaviour survey, representative of the population level.SettingGeneral rural population in Chiang Rai (Thailand) and Salavan (Lao PDR), surveyed between November 2017 and May 2018.Participants2141 adult members (≥18 years) of the general rural population, representing 712 000 villagers.Outcome measuresAntibiotic-related knowledge, attitudes and practices across sites and healthcare access channels.FindingsVillagers were aware of antibiotics (Chiang Rai: 95.7%; Salavan: 86.4%; p<0.001) and drug resistance (Chiang Rai: 74.8%; Salavan: 62.5%; p<0.001), but the usage of technical concepts for antibiotics was dwarfed by local expressions like ‘anti-inflammatory medicine’ in Chiang Rai (87.6%; 95% CI 84.9% to 90.0%) and ‘ampi’ in Salavan (75.6%; 95% CI 71.4% to 79.4%). Multivariate linear regression suggested that attitudes against over-the-counter antibiotics were linked to 0.12 additional antibiotic use episodes from public healthcare providers in Chiang Rai (95% CI 0.01 to 0.23) and 0.53 in Salavan (95% CI 0.16 to 0.90).ConclusionsLocally specific conceptions and counterintuitive practices around antimicrobials can complicate AMR communication efforts and entail unforeseen consequences. Overcoming ‘knowledge deficits’ alone will therefore be insufficient for global AMR behaviour change. We call for an expansion of behavioural AMR strategies towards ‘AMR-sensitive interventions’ that address context-specific upstream drivers of antimicrobial use (eg, unemployment insurance) and complement education and awareness campaigns.Trial registration numberClinicaltrials.gov identifier NCT03241316.