Barriers and facilitators and the need for a clinical guideline for microbiological diagnostic testing in the hospital: a qualitative and quantitative study.

The appropriate use of microbiological investigations is an important cornerstone of antibiotic stewardship programmes, but receives relatively limited attention. This study aimed to identify influencing factors in performing microbiological diagnostic tests and to assess the need for a clinical guideline. We performed a qualitative (focus group) and quantitative (online questionnaire survey) study among medical specialists and residents to identify physicians' considerations in performing microbiological diagnostic tests and to assess the need for a diagnostic guideline. The questionnaire consisted of 14 statements, divided into three categories: knowledge, influencing factors and presence of guidelines. The questionnaire was sent to physicians of the departments of internal medicine, intensive care, paediatrics and pulmonology in five hospitals in the Netherlands. Sub-analyses for medical specialists versus residents and for paediatric versus non-paediatric departments were performed. We included 187 completed questionnaires in our analyses. The physicians reported having adequate knowledge on methods, time-to-result and accuracy, but inadequate knowledge on costs of the tests. Patients' clinical condition, comorbidity, local guidelines and accuracy of tests were appraised as the four most important influencing factors to perform tests. Over 70% (132/187) of physicians reported being interested in a guideline for microbiological diagnostic testing. Fifteen physicians (8.0%) provided additional comments. This study identifies the influencing factors to microbiological testing and shows the demand for a clinical guideline among physicians. IMPORTANCE: Microbiological diagnostic tests are an important cornerstone within antibiotic stewardship programmes [1-5]. These programmes aim to ameliorate the appropriate use of antibiotics and thus improve clinical outcomes of infectious diseases, whilst reducing the emergence of antimicrobial resistance [6]. However, inappropriate microbiological testing is a widely recognised problem [7-12], and influencing factors to testing have not been studied in the past. Our research shows the demand for a clinical guideline among physicians, and it identifies their influencing factors to testing. These results can be used to create a clinical guideline for microbiological diagnostic testing, thus supporting antibiotic stewardship programmes and reducing antimicrobial resistance.

The antibiotic checklist: an observational study of the discrepancy between reported and actually performed checklist items.

BACKGROUND: Checklists are increasingly used to measure quality of care. Recently we implemented an antibiotic checklist in nine Dutch hospitals and showed that use of the checklist resulted in more appropriate antibiotic use. While more appropriate antibiotic use was associated with a reduction in length of stay, use of the checklist in itself was not. In the current study we explored discrepancies between reported and actually performed checklist items at the patient level to test the validity of checklist answers, to evaluate whether discrepancies between reported and actually performed checklist items could explain the lack of effect of checklist use on length of stay, and to identify missed opportunities for performance per checklist item. METHODS: Checklist answers represented reported performance. Actual performance was assessed by data from the patients' medical files. Reported and actually performed checklist items could be 'both YES'; 'both NO'; 'YES reported, NOT actually performed'; or 'NO reported, YES actually performed'. We determined an overall 'both YES' score per checklist, and used mixed models to evaluate whether an association existed between this overall score and patient's length of hospital stay. Finally, we analysed whether the items that were not actually performed, could have been performed. RESULTS: Between January and October 2015 physicians filled in 1207 checklists. In total 7881 items were checked. Most items were 'both YES' (3392/7881, 43.0%) or 'both NO' (2601/7881, 33.0%). The number of 'YES reported, NOT actually performed' items was 1628/7881 (20.7%) compared to 260/7881 (3.3%) 'NO reported, YES actually performed' items. The level of discrepancy between reported and actually performed items differed per checklist item. The item 'prescribe antibiotic treatment according to the local guideline' had the highest percentage of 'YES reported, NOT actually performed' items, namely 45.1%. A higher overall 'both YES' score of the checklist was significantly associated with a shorter length of hospital stay. Of all checklist items 21.8% were not performed while they could have been performed. CONCLUSIONS: Checklist answers do not accurately assess actual provided care. As actual performance of the antibiotic checklist items is associated with length of stay, efforts to increase actual performance appear to be justified.

The economic evaluation of an antibiotic checklist as antimicrobial stewardship intervention.

OBJECTIVES: An antibiotic checklist was introduced in nine Dutch hospitals to improve appropriate antibiotic use. We estimated the cost-effectiveness of checklist use. METHODS: We compared 853 patients treated with an antibiotic before checklist introduction (usual care group) with 1207 patients treated after introduction (checklist group). We calculated the change of costs between these groups per unit effect [incremental cost-effectiveness ratio (ICER)]: per extra patient receiving appropriate treatment; and per day reduction in length of hospital stay (LOS). We also calculated the benefit-to-cost ratio per day reduction in LOS. Finally, we estimated the number of checklists after which the expected benefits would compensate for costs in one hospital. RESULTS: The cost of checklist use per patient was €10.10. Of the usual care patients, 48.8% received appropriate antibiotic treatment compared with 67.5% of the checklist patients (+18.7%). The ICER was €54.01 (1010/18.7) per extra patient with appropriate treatment. In a model calculation the expected effect of appropriate antibiotic use was a reduction in LOS of 1.05 days, which was extrapolated to a reduction of 19.64 hospital days per 100 patients. The ICER was €51.43 (1010/19.64) per day reduction in LOS. The estimated benefit of a 1 day reduction was €611. The benefit-to-cost ratio was 11.9 (611/51.43) per day reduction in LOS, indicating a cost saving of €12 for every euro spent on checklist use. The benefits would compensate for costs after use of 11 checklists. CONCLUSIONS: Efforts for further implementation of the antibiotic checklist can be justified by potential economic benefits.

A cluster randomized trial for the implementation of an antibiotic checklist based on validated quality indicators: the AB-checklist.

BACKGROUND: Recently we developed and validated generic quality indicators that define 'appropriate antibiotic use' in hospitalized adults treated for a (suspected) bacterial infection. Previous studies have shown that with appropriate antibiotic use a reduction of 13% of length of hospital stay can be achieved. Our main objective in this project is to provide hospitals with an antibiotic checklist based on these quality indicators, and to evaluate the introduction of this checklist in terms of (cost-) effectiveness. METHODS/DESIGN: The checklist applies to hospitalized adults with a suspected bacterial infection for whom antibiotic therapy is initiated, at first via the intravenous route. A stepped wedge study design will be used, comparing outcomes before and after introduction of the checklist in nine hospitals in the Netherlands. At least 810 patients will be included in both the control and the intervention group. The primary endpoint is length of hospital stay. Secondary endpoints are appropriate antibiotic use measured by the quality indicators, admission to and duration of intensive care unit stay, readmission within 30 days, mortality, total antibiotic use, and costs associated with implementation and hospital stay. Differences in numerical endpoints between the two periods will be evaluated with mixed linear models; for dichotomous outcomes generalized estimating equation models will be used. A process evaluation will be performed to evaluate the professionals' compliance with use of the checklist. The key question for the economic evaluation is whether the benefits of the checklist, which include reduced antibiotic use, reduced length of stay and associated costs, justify the costs associated with implementation activities as well as daily use of the checklist. DISCUSSION: If (cost-) effective, the AB-checklist will provide physicians with a tool to support appropriate antibiotic use in adult hospitalized patients who start with intravenous antibiotics. TRIAL REGISTRATION: Dutch trial registry: NTR4872.

Does dose reduction of renally cleared antibiotics in patients with impaired renal function lead to adequate drug exposure? A systematic review.

BACKGROUND: There is inconsistency between many guidelines in the recommended dose reduction of renally cleared antibiotics in patients with impaired renal function. OBJECTIVES: This systematic review summarizes the available evidence on the adequacy of the recommended dose reduction in terms of achieving sufficient antibiotic drug exposure or pharmacokinetic/pharmacodynamic target attainment after treatment with these reduced doses. DATA SOURCES: We systematically searched Ovid Medline and Embase from inception (respectively 1946 and 1947) through July 2019. STUDY ELIGIBILITY CRITERIA: All studies reporting antibiotic drug exposure and/or pharmacokinetic/pharmacodynamic (PK/PD) target attainment after dose reduction of antibiotics in patients with impaired renal function. PARTICIPANTS: Adult patients with or without infections. INTERVENTIONS: Administration of reduced doses of antibiotics (orally, intravenously or intramuscularly). METHODS: The reduced dose was considered adequate when the most relevant parameters of drug exposure or PK/PD target attainment in patients with impaired renal function were within a range of 80% to 125% of that patients with adequate renal function receiving a regular dose (reference) or when PK/PD target attainment was attained in at least 90% of the patients with impaired renal function, regardless of the lack of a reference group. RESULTS: Twenty-seven of the 4202 identified studies were included. The quality of 15 of 27 studies was fair, and most studies were of ß-lactams (12/27). Best evidence was available for meropenem: four studies were included, of which two studies were of good quality. Drug exposure for meropenem is 158% to 286% higher in patients with impaired renal function receiving reduced doses compared to patients with adequate renal function receiving regular doses. For all other antibiotics, a maximum of one good-quality study could be identified. CONCLUSIONS: No good-quality evidence on the recommended dose reduction of renally cleared antibiotics in patients with impaired renal function is present, with the exception of meropenem.

Pharmacokinetic/pharmacodynamic target attainment of ciprofloxacin in adult patients on general wards with adequate and impaired renal function.

Limited prospective data on pharmacokinetic/pharmacodynamic (PK/PD) target attainment of ciprofloxacin in patients with adequate and impaired renal function (eGFR <30 mL/min/1.73m2) are available in the literature. We aimed to investigate whether the PK/PD target (AUC/MIC ≥125) is attained in patients with adequate and impaired renal function receiving regular and reduced ciprofloxacin doses. This prospective observational cohort study included adult patients on general wards treated with ciprofloxacin. Three blood samples per patient were obtained for ciprofloxacin concentration measurement. Individual AUCs were calculated using a population PK model developed by non-linear mixed-effects modelling. Forty patients were included, of whom eight had impaired renal function and were treated with a guideline-recommended reduced dose. Using the clinical breakpoint MIC of the most isolated bacteria (Escherichia coli, 0.25 mg/L), AUC0-24/MIC ≥125 was attained in 13/32 (41%) patients with adequate renal function receiving regular doses and in 1/8 (13%) patients with impaired renal function receiving reduced doses. Median drug exposure (AUC0-24) for patients with impaired renal function was 19.0 [interquartile range (IQR) 14.2-23.3] mg/L•h, which was statistically significantly lower than that for patients with adequate renal function [29.3 (IQR 25.0-36.0) mg/L•h] (P < 0.01). AUC0-24/MIC ≥125 is not attained in the majority of adult patients on general wards for clinically relevant bacteria with MICs at or just below the clinical breakpoint. The risk of not attaining the target appears to be highest in patients with impaired renal function receiving guideline-recommended reduced doses, as drug exposure is significantly lower in these patients.