Mitigating antimicrobial resistance (AMR) using implementation research: a development funder's approach.

Despite the escalating burden of antimicrobial resistance (AMR), the global response has not sufficiently matched the scale and scope of the issue, especially in low- and middle-income countries (LMICs). While many countries have adopted national action plans to combat AMR, their implementation has lagged due to resource constraints, dysfunctional multisectoral coordination mechanisms and, importantly, an under-recognized lack of technical capacity to adapt evidence-based AMR mitigation interventions to local contexts. AMR interventions should be tailored, context-specific, cost-effective and sustainable. The implementation and subsequent scale-up of these interventions require multidisciplinary intervention-implementation research (IIR). IIR involves both quantitative and qualitative approaches, occurs across a three-phase continuum (proof of concept, proof of implementation and informing scale-up), and across four context domains (inner setting, outer setting, stakeholders and the implementation process). We describe the theoretical underpinnings of implementation research (IR), its various components, and how to construct different IR strategies to facilitate sustainable uptake of AMR interventions. Additionally, we provide real-world examples of AMR strategies and interventions to demonstrate these principles in practice. IR provides a practical framework to implement evidence-based and sustainable AMR mitigation interventions.

Diagnosis of urinary tract infection based on symptoms: how are likelihood ratios affected by age? a diagnostic accuracy study.

OBJECTIVES: The aim of this study was to investigate the impact of age on the diagnostic properties of typical symptoms of urinary tract infection (UTI) in women presenting in general practice with symptoms suggestive of UTI with significant bacteriuria as the reference standard. DESIGN: Diagnostic accuracy study. SETTING: General practice, Copenhagen, Denmark. PARTICIPANTS: Adult 15 years or older. Women presenting in general practice with symptoms suggestive of UTI where urine was collected for investigation. PRIMARY AND SECONDARY OUTCOME MEASURES: Accuracy of four symptoms of UTI (dysuria, frequency, urge and abdominal pain) in six different age groups. RESULTS: 90 practices included 1178 adult women. The prevalence of bacteriuria varied between 30% in women aged 30-44 years and 67% in women aged 75-89 years. The likelihood ratios for dysuria varied between age groups with the best performance in women aged 15-29 (positive likelihood ratio (pLR): 1.62 (1.30-1.94), negative likelihood ratio (nLR): 0.36 (0.19-0.54)) and women aged 30-44 (pLR: 1.74 (1.30-2.17), nLR: 0.48 (0.27-0.68)). CIs included or approximated one for the remaining symptoms in most age groups. When symptoms were combined to calculate post-test probabilities, the combined effect of the varying prevalence of bacteriuria and the varying diagnostic values resulted in a large variation of the post-test probabilities between age groups. CONCLUSIONS: The diagnostic value of symptoms of UTI as well as the prevalence of bacteriuria in women presenting to general practice with suspected UTI vary between age groups with considerable clinical implications. Diagnostic studies should take demographics such as age into consideration. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT02698332.

Predicting the use of antibiotics after initial symptomatic treatment of an uncomplicated urinary tract infection: analyses performed after a randomised controlled trial.

OBJECTIVE: To predict antibiotic use after initial treatment with ibuprofen using data from a randomised controlled trial comparing ibuprofen to pivmecillinam in the treatment of women with symptoms of an uncomplicated urinary tract infection (UTI). SETTING: 16 sites in a primary care setting in Norway, Sweden and Denmark. PARTICIPANTS: Data from 181 non-pregnant women aged 18-60 presenting with symptoms of uncomplicated UTI, initially treated with ibuprofen. METHODS: Using the least absolute shrinkage and selection operator logistic regression model, we conducted analyses to see if baseline information could help us predict which women could be treated with ibuprofen without risking treatment failure and which women should be recommended antibiotics. RESULTS: Of the 143 women included in the final analysis, 77 (53.8%) recovered without antibiotics and 66 (46.2 %) were subsequently prescribed antibiotics. In the unadjusted binary logistic regression, the number of days with symptoms before inclusion (<3 days) and feeling moderately unwell or worse (≥4 on a scale of 0-6) were significant predictors for subsequent antibiotic use. In the adjusted model, no predictors were significantly associated with subsequent antibiotic use. The area under the curve of the final model was 0.66 (95% CI: 0.57 to 0.74). CONCLUSION: We did not find any baseline information that significantly predicted the use of antibiotic treatment. Identifying women who need antibiotic treatment to manage their uncomplicated UTI is still challenging. Larger data sets are needed to develop models that are more accurate. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT01849926).

Predictors for antibiotic prescribing in patients with exacerbations of COPD in general practice.

BACKGROUND: The aim of this study was to describe the antibiotic prescribing rate in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), to analyse predictors for antibiotic prescribing and to explore the influence of the use C-reactive protein (CRP) rapid test. METHODS: A cross-sectional study was carried out in January and February 2008 in primary care. General practitioners (GPs) from six countries (Denmark, Sweden, Lithuania, Russia, Spain and Argentina) registered all patients with AECOPD during a 3-week period. A multilevel logistic regression model was estimated using two hierarchical levels, (i) patients and (ii) physicians, and was used to analyse the association between antibiotic prescribing and potential predictors for antibiotic use: patients' age and gender, duration and symptoms and signs of exacerbations (fever, cough, dyspnoea, sputum volume and purulence) and the results of the CRP test. RESULTS: A total of 617 GPs registered 1233 patients with AECOPD. A total of 970 patients (79%) were prescribed antibiotics, varying from 49% (Denmark) to 93% (Russia). The presence of purulent sputum was the strongest predictor for antibiotic treatment (odds ratio [OR] 8.7; 95% confidence interval [CI] 5.9-12.8). CRP determination was carried out mainly in Denmark and Sweden and its use was the strongest protective factor for antibiotic therapy (OR 0.3; 95% CI 0.2-0.6). GPs that used CRP testing weighted purulent sputum lower than GPs who did not use CRP testing. CRP values had a strong influence on the antibiotic prescribing rate. CONCLUSIONS: Antibiotic treatment for AECOPD is very high. This study shows that GPs performing CRP rapid tests prescribe fewer antibiotics than those who do not.