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Implementation of a clinical decision rule for selecting empiric treatment for invasive aspergillosis in a setting with high triazole resistance.

ABSTRACT: World-wide, emerging triazole resistance increasingly complicates treatment of invasive aspergillosis (IA). In settings with substantial (>10%) prevalence of triazole resistance, empiric combination therapy with both a triazole and liposomal amphotericin B (LAmB) can be considered because of the low yields of susceptibility testing. To avoid toxicity while optimizing outcome, a strategy with monotherapy would be preferable. A newly designed treatment algorithm based on literature and expert consensus provided guidance for empiric monotherapy with either voriconazole or LAmB. Over a four and a half year period, all adult patients in our hospital treated for IA were included and patient data were collected. An independent committee reviewed the attributability of death to IA for each patient. Primary outcomes were 30- and 100-day crude mortality and attributable mortality. In total, 110 patients were treated according to the treatment algorithm. Fifty-six patients (51%) were initially treated with voriconazole and 54 patients (49%) with LAmB. Combined attributable and contributable mortality was 13% within 30 days and 20% within 100 days. Treatment switch to LAmB was made in 24/56 (43%) of patients who were initially treated with voriconazole. Combined contributable and attributable 100-day mortality in this subgroup was 21% and was not increased when compared with patients initially treated with LAmB (P = 0.38). By applying a comprehensive clinical decision algorithm, an antifungal-sparing regime was successfully introduced. Further research is warranted to explore antifungal treatment strategies that account for triazole-resistance.

Lay summary

Due to resistance of Aspergillus against triazoles, combination therapy with liposomal amphotericin B (LAmB) is applied more often as primary therapy against invasive aspergillosis. This study presents the results of a decision tool which differentiated between triazole or LAmB monotherapy.

SUBMITTER: van de Peppel RJ

PROVIDER: S-EPMC8653343 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundOveruse of fluoroquinolone antibiotics is associated with outbreaks of methicillin-resistant Staphylococcus aureus and of Clostridium difficile-associated diarrhea and increasing resistance in gram-negative organisms. Over the past decade, resistance of Escherichia coli to ciprofloxacin has increased in the Regina Qu'Appelle Health Region. In August 2011, an exploratory audit of the Regina General Hospital (RGH) emergency department showed that 20% of new antibiotic orders were for fluoroquinolones, and 60% of these new fluoroquinolone orders were for ciprofloxacin. It was postulated that ciprofloxacin was predominantly prescribed for outpatients with urinary tract infection.ObjectiveTo develop, implement, and evaluate a best-practice algorithm for the empiric treatment of uncomplicated urinary tract infection in the RGH emergency department, as part of an educational initiative for emergency physicians.MethodsA literature review was conducted and local antibiogram data were analyzed to establish a best-practice algorithm for treatment of uncomplicated urinary tract infection in outpatients seen in the emergency department. A chart review was conducted from January to March 2011 to establish a baseline of empiric antibiotic use. An educational strategy targeting emergency physicians described changes in antibiotic resistance patterns in the health region, principles of antimicrobial stewardship, drivers of resistance, and the results of a literature review of best practice for urinary tract infection in outpatients. A post-intervention audit was conducted from January to March 2012 to determine changes in practice.ResultsComparison of results from the post-intervention audit with baseline data showed that adherence to best practice increased significantly, from 41% (39/96) before the intervention to 66% (50/76) after the intervention (odds ratio [OR] 2.81, 95% confidence interval [CI] 1.51-5.25; p < 0.001). There was also a significant change in overall antibiotic selection (OR 0.25, 95% CI 0.11-0.58; p < 0.001). Further analysis suggested that this significant change was driven by a decrease in use of ciprofloxacin, from 32% (31/96) to 11% (8/76).ConclusionCreation of a best-practice algorithm and education focused on emergency physicians significantly increased adherence to best practice and optimized antibiotic prescribing for outpatients with uncomplicated urinary tract infection by limiting overuse of fluoroquinolones, primarily ciprofloxacin.

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Implementation of a clinical decision rule for selecting empiric treatment for invasive aspergillosis in a setting with high triazole resistance.

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