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van Werkhoven, C. H.

Publications and source records attributed to van Werkhoven, C. H..

3 recordsLinked to original sources

Diagnostic Prediction Tools For Bacteraemia Caused By 3rd Generation Cephalosporin-Resistant Enterobacteriaceae In Suspected Bacterial Infections: A Nested Case-Control Study

ObjectivesCurrent guidelines for empirical antibiotic treatment poorly predict the presence of 3rd generation cephalosporin resistant Enterobacteriaceae (3GC-R EB) as a cause of infection, thereby increasing unnecessary carbapenem use. We aimed to develop diagnostic scoring systems to better predict the presence of 3GC-R EB as a cause of bacteraemia.\n\nMethodsA retrospective nested case-control study was performed that included patients [≥]18 years in whom blood cultures were obtained and intravenous antibiotics were initiated. Each patient with 3GC-R EB bacteraemia was matched to four control infection episodes within the same hospital, based on blood culture date and onset location (community or hospital). Starting from 32 described clinical risk factors at infection onset, selection strategies were used to derive scoring systems for the probability of community- and hospital-onset 3GC-R EB bacteraemia.\n\nResults3GC-R EB bacteraemia occurred in 90 of 22,506 (0.4%) community-onset and in 82 of 8,110 (1.0%) hospital-onset infections, and these cases were matched to 360 community-onset and 328 hospital-onset control episodes, respectively. The derived community-onset and hospital-onset scoring system consisted of 6 and 9 predictors, respectively, with c-statistics of 0.807 (95% confidence interval 0.756-0.855) and 0.842 (0.794-0.887). With selected score cutoffs, the models identified 3GC-R EB bacteraemia with equal sensitivity as existing guidelines, but reduced the proportion of patients classified as at risk for 3GC-R EB bacteraemia (i.e. eligible for empiric carbapenem therapy) with 40% in patients with community-onset and 49% in patients with hospital-onset infection.\n\nConclusionsThese prediction rules for 3GC-R EB bacteraemia may reduce unnecessary empiric carbapenem use.

epidemiology

Cardiac events after macrolides or fluoroquinolones in patients hospitalized for community-acquired pneumonia: post-hoc analysis of a cluster-randomized trial

BackgroundGuidelines recommend macrolides and fluoroquinolones in patients hospitalized with community-acquired pneumonia (CAP), but their use has been associated with cardiac events.\n\nObjectiveTo quantify associations between macrolide and fluoroquinolone use and cardiac events in patients hospitalized with CAP in non-ICU wards.\n\nDesignPost-hoc analysis of a cluster-randomized trial\n\nSettingSix hospitals in the Netherlands\n\nPatientsCAP patients admitted to non-ICU wards and without a cardiac event on admission\n\nMeasurementsCause-specific hazard ratios (HRs) were calculated for effects of time-dependent macrolide and fluoroquinolone exposure on cardiac events, defined as occurrence of new or worsening heart failure, arrhythmia, or myocardial ischemia during hospitalization.\n\nResultsCardiac events occurred in 146 (6.9%) of 2,107 patients and included episodes of heart failure (n=101, 4.8%), arrhythmia (n=53, 2.5%), and myocardial ischemia (n=14, 0.7%). Cardiac events occurred in 11 of 207 (5.3%), 18 of 250 (7.2%), and 31 of 277 (11.2%) patients exposed to azithromycin, clarithromycin, and erythromycin for at least one day, respectively, and in 9 of 234 (3.8%), 5 of 194 (2.6%), and 23 of 566 (4.1%) patients exposed to ciprofloxacin, levofloxacin, and moxifloxacin, respectively. Hazard ratios for any cardiac event, adjusted for confounding, were 0.89 (95% confidence interval (CI) 0.48 to 1.67), 1.06 (95% CI 0.61 to 1.83) and 1.68 (95% CI 1.07 to 2.62) for azithromycin, clarithromycin, and erythromycin, respectively, and adjusted hazard ratios were 0.86 (95% CI 0.47 to 1.57), 0.42 (95% CI 0.18 to 0.96) and 0.62 (95% CI 0.39 to 0.99) for ciprofloxacin, levofloxacin, and moxifloxacin, respectively. Erythromycin was associated with an adjusted hazard ratio of 2.08 (95% CI 1.25 to 3.46) for heart failure.\n\nLimitationsPossibility of confounding by indication and observational bias\n\nConclusionsAmong patients with CAP hospitalized to non-ICU wards, erythromycin use was associated with a 68% increased risk of hospital-acquired cardiac events, mainly heart failure. Levofloxacin and moxifloxacin were associated with a lower risk of heart failure.\n\nRegistrationThe original trial was registered under ClinicalTrials.gov Identifier NCT01660204\n\nFunding SourceThe Netherlands Organization for Health Research and Development (ZONmw, Health care efficiency research, project id: 171202002).

epidemiology

Response Adjusted for Days of Antibiotic Risk (RADAR): evaluation of a novel method to analyze antibiotic stewardship interventions

OBJECTIVESThe Response Adjusted for Days of Antibiotic Risk (RADAR)-statistic was proposed to improve efficiency of antibiotic stewardship trials. We studied the behavior of RADAR in a non-inferiority trial in which a beta-lactam monotherapy strategy (BL, n=656) was non-inferior to fluoroquinolone monotherapy (FQL, n=888) for moderately-severe community-acquired pneumonia (CAP) patients.\n\nMETHODSPatients were ranked according to clinical outcome, using five or eight categories, and antibiotic use. RADAR was calculated as the probability that the BL group had a more favorable ranking than the FQL group. To investigate the sensitivity of RADAR to detrimental clinical outcome we simulated increasing rates of 90-day mortality in the BL group and performed the RADAR and non-inferiority analysis.\n\nRESULTSThe RADAR of the BL-group compared to the FQL group was 60.3% (95% confidence interval 57.9%-62.7%) using five and 58.4% (95% CI 56.0%-60.9%) using eight clinical outcome categories, all in favor of BL. Sample sizes for RADAR were 250 and 580 patients per study arm using five or eight clinical outcome categories, respectively, reflecting 38% and 89% of the original non-inferiority sample size calculation. With simulated mortality rates, loss of non-inferiority of the BL-group occurred at a relative risk of 1.125 in the conventional analysis, whereas using RADAR the BL-group lost superiority at a relative risk of mortality of 1.25 and 1.5, with eight and five clinical outcome categories, respectively.\n\nCONCLUSIONSRADAR favored BL over FQL therapy for CAP. Although RADAR required fewer patients than conventional non-inferiority analysis, the statistic was less sensitive to detrimental outcomes.

epidemiology