Purpose: COVID-19 associated pulmonary aspergillosis (CAPA) is associated with increased morbidity and mortality in ICU patients. We investigated the incidence of, risk factors for and potential... Show morePurpose: COVID-19 associated pulmonary aspergillosis (CAPA) is associated with increased morbidity and mortality in ICU patients. We investigated the incidence of, risk factors for and potential benefit of a pre-emptive screening strategy for CAPA in ICUs in the Netherlands/Belgium during immunosuppressive COVID-19 treatment.Materials and methods: A retrospective, observational, multicentre study was performed from September 2020-April 2021 including patients admitted to the ICU who had undergone diagnostics for CAPA. Patients were classified based on 2020 ECMM/ISHAM consensus criteria.Results: CAPA was diagnosed in 295/1977 (14.9%) patients. Corticosteroids were administered to 97.1% of patients and interleukin-6 inhibitors (anti-IL-6) to 23.5%. EORTC/MSGERC host factors or treatment with anti-IL-6 with or without corticosteroids were not risk factors for CAPA. Ninety-day mortality was 65.3% (145/222) in patients with CAPA compared to 53.7% (176/328) without CAPA (p = 0.008). Median time from ICU admission to CAPA diagnosis was 12 days. Pre-emptive screening for CAPA was not associated with earlier diagnosis or reduced mortality compared to a reactive diagnostic strategy.Conclusions: CAPA is an indicator of a protracted course of a COVID-19 infection. No benefit of pre-emptive screening was observed, but prospective studies comparing pre-defined strategies would be required to confirm this observation. Show less
Background The Dutch Working Party on Antibiotic Policy (SWAB) in collaboration with relevant professional societies, has updated their evidence-based guidelines on empiric antibacterial therapy of... Show moreBackground The Dutch Working Party on Antibiotic Policy (SWAB) in collaboration with relevant professional societies, has updated their evidence-based guidelines on empiric antibacterial therapy of sepsis in adults. Methods Our multidisciplinary guideline committee generated ten population, intervention, comparison, and outcome (PICO) questions relevant for adult patients with sepsis. For each question, a literature search was performed to obtain the best available evidence and assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The quality of evidence for clinically relevant outcomes was graded from high to very low. In structured consensus meetings, the committee formulated recommendations as strong or weak. When evidence could not be obtained, recommendations were provided based on expert opinion and experience (good practice statements). Results Fifty-five recommendations on the antibacterial therapy of sepsis were generated. Recommendations on empiric antibacterial therapy choices were differentiated for sepsis according to the source of infection, the potential causative pathogen and its resistance pattern. One important revision was the distinction between low, increased and high risk of infection with Enterobacterales resistant to third generation cephalosporins (3GRC-E) to guide the choice of empirical therapy. Other new topics included empirical antibacterial therapy in patients with a reported penicillin allergy and the role of pharmacokinetics and pharmacodynamics to guide dosing in sepsis. We also established recommendations on timing and duration of antibacterial treatment. Conclusions Our multidisciplinary committee formulated evidence-based recommendations for the empiric antibacterial therapy of adults with sepsis in The Netherlands. Show less
Background and objective: Previous pharmacokinetic (PK) studies of ciprofloxacin in intensive care (ICU) patients have shown large differences in estimated PK parameters, suggesting that further... Show moreBackground and objective: Previous pharmacokinetic (PK) studies of ciprofloxacin in intensive care (ICU) patients have shown large differences in estimated PK parameters, suggesting that further investigation is needed for this population. Hence, we performed a pooled population PK analysis of ciprofloxacin after intravenous administration using individual patient data from three studies. Additionally, we studied the PK differences between these studies through a post-hoc analysis.Methods: Individual patient data from three studies (study 1, 2, and 3) were pooled. The pooled data set consisted of 1094 ciprofloxacin concentration-time data points from 140 ICU patients. Nonlinear mixed-effects modeling was used to develop a population PK model. Covariates were selected following a stepwise covariate modeling procedure. To analyze PK differences between the three original studies, random samples were drawn from the posterior distribution of individual PK parameters. These samples were used for a simulation study comparing PK exposure and the percentage of target attainment between patients of these studies.Results: A two-compartment model with first-order elimination best described the data. Inter-individual variability was added to the clearance, central volume, and peripheral volume. Inter-occasion variability was added to clearance only. Body weight was added to all parameters allometrically. Estimated glomerular filtration rate on ciprofloxacin clearance was identified as the only covariate relationship resulting in a drop in inter-individual variability of clearance from 58.7 to 47.2%. In the post-hoc analysis, clearance showed the highest deviation between the three studies with a coefficient of variation of 14.3% for posterior mean and 24.1% for posterior inter-individual variability. The simulation study showed that following the same dose regimen of 400 mg three times daily, the area under the concentration-time curve of study 3 was the highest with a mean area under the concentration-time curve at 24 h of 58 mg·h/L compared with that of 47.7 mg·h/L for study 1 and 47.6 mg·h/L for study 2. Similar differences were also observed in the percentage of target attainment, defined as the ratio of area under the concentration-time curve at 24 h and the minimum inhibitory concentration. At the epidemiological cut-off minimum inhibitory concentration of Pseudomonas aeruginosa of 0.5 mg/L, percentage of target attainment was only 21%, 18%, and 38% for study 1, 2, and 3, respectively.Conclusions: We developed a population PK model of ciprofloxacin in ICU patients using pooled data of individual patients from three studies. A simple ciprofloxacin dose recommendation for the entire ICU population remains challenging owing to the PK differences within ICU patients, hence dose individualization may be needed for the optimization of ciprofloxacin treatment. Show less
Scope: The Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized... Show moreScope: The Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized adults with a respiratory infection and suspected or proven 2019 Coronavirus disease (COVID-19).Methods: We performed a literature search to answer four key questions. The committee graded the evidence and developed recommendations by using Grading of Recommendations Assessment, Development, and Evaluation methodology.Questions addressed by the guideline and Recommendations: We assessed evidence on the risk of bacterial infections in hospitalized COVID-19 patients, the associated bacterial pathogens, how to diagnose bacterial infections and how to treat bacterial infections. Bacterial co-infection upon admission was reported in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred up to 15%. No or very low quality evidence was found to answer the other key clinical questions. Although the evidence base on bacterial infections in COVID-19 is currently limited, available evidence supports restrictive antibiotic use from an antibiotic stewardship perspective, especially upon admission. To support restrictive antibiotic use, maximum efforts should be undertaken to obtain sputum and blood culture samples as well as pneumococcal urinary antigen testing. We suggest to stop antibiotics in patients who started antibiotic treatment upon admission when representative cultures as well as urinary antigen tests show no signs of involvement of bacterial pathogens after 48 hours. For patients with secondary bacterial respiratory infection we recommend to follow other guideline recommendations on antibacterial treatment for patients with hospital-acquired and ventilator-associated pneumonia. An antibiotic treatment duration of five days in patients with COVID-19 and suspected bacterial respiratory infection is recommended upon improvement of signs, symptoms and inflammatory markers. Larger, prospective studies about the epidemiology of bacterial infections in COVID-19 are urgently needed to confirm our conclusions and ultimately prevent unnecessary antibiotic use during the COVID-19 pandemic. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. Show less
Kallen, M.C.; Roos-Blom, M.J.; Dongelmans, D.A.; Schouten, J.A.; Gude, W.T.; Jonge, E. de; ... ; Keizer, N.F. de 2018
