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Objectives:Obesity may alter the pharmacokinetics of β-lactams. The goal of this study was to evaluate if and why serum concentrations are inadequate when standard β-lactam regimens are administered to obese, non-critically ill patients.Subjects and methods:During first year, we consecutively included infected, obese patients (body mass index (BMI) ⩾30 kg m−2) who received meropenem (MEM), piperacillin-tazobactam (TZP) or cefepime/ceftazidime (CEF). Patients with severe sepsis or septic shock, or those hospitalized in the intensive care unit were excluded. Serum drug concentrations were measured twice during the elimination phase by high-performance liquid chromatography. We evaluated whether free or total drug concentrations were >1 time (fT>minimal inhibition concentration (MIC)) or >4 times (T>4MIC) the clinical breakpoints for Pseudomonas aeruginosa during optimal periods of time: ⩾40% for MEM, ⩾50% for TZP and ⩾70% for CEF.Results:We included 56 patients (median BMI: 36 kg m−2): 14 received MEM, 31 TZP and 11 CEF. The percentage of patients who attained target fT>MIC and T>4MIC were 93% and 21% for MEM, 68% and 19% for TZP, and 73% and 18% for CEF, respectively. High creatinine clearance (107 (range: 6–398) ml min−1) was the only risk factor in univariate and multivariate analyses to predict insufficient serum concentrations.Conclusions:In obese, non-critically ill patients, standard drug regimens of TZP and CEF resulted in insufficient drug concentrations to treat infections due to less susceptible bacteria. Augmented renal clearance was responsible for these low serum concentrations. New dosage regimens need to be explored in this patient population (EUDRA-CT: 2011-004239-29).

Highlights Early cytokine measurement after hospitalization predicts disease progression A score combining the results of IL-6, IL-8 and IL-10 allows to predict with a very high performance: The severity of the disease (IL-6 * IL-8 * IL-10 score : threshold value of 2068 pg/mL) The need for intensive care (IL-6 * IL-10 score: cut-off value of 178 pg/mL)

BackgroundSeveral randomised clinical trials have studied convalescent plasma for coronavirus disease 2019 (COVID-19) using different protocols, with different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibody titres, at different time-points and severities of illness.MethodsIn the prospective multicentre DAWn-plasma trial, adult patients hospitalised with COVID-19 were randomised to 4 units of open-label convalescent plasma combined with standard of care (intervention group) or standard of care alone (control group). Plasma from donors with neutralising antibody titres (50% neutralisation titre (NT50)) ≥1/320 was the product of choice for the study.ResultsBetween 2 May 2020 and 26 January 2021, 320 patients were randomised to convalescent plasma and 163 patients to the control group according to a 2:1 allocation scheme. A median (interquartile range) volume of 884 (806–906) mL) convalescent plasma was administered and 80.68% of the units came from donors with neutralising antibody titres (NT50) ≥1/320. Median time from onset of symptoms to randomisation was 7 days. The proportion of patients alive and free of mechanical ventilation on day 15 was not different between both groups (convalescent plasma 83.74% (n=267) versus control 84.05% (n=137)) (OR 0.99, 95% CI 0.59–1.66; p=0.9772). The intervention did not change the natural course of antibody titres. The number of serious or severe adverse events was similar in both study arms and transfusion-related side-effects were reported in 19 out of 320 patients in the intervention group (5.94%).ConclusionsTransfusion of 4 units of convalescent plasma with high neutralising antibody titres early in hospitalised COVID-19 patients did not result in a significant improvement of clinical status or reduced mortality.

While the COVID-19 epidemic occurred since December 2019, as of end April 2020, no treatment has been validated or invalidated by accurate clinical trials. Use of hydroxychloroquine has been popularised on mass media and put forward as a valid treatment option without strong evidence of efficacy. Hydroxychloroquine (HCQ) has its own side effects, some of which are very serious like acute haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. Side effects may be worse than the disease itself. Belgian national treatment guidelines recommend the use of HCQ in mild to severe COVID-19 disease. As opinions, politics, media and beliefs are governing COVID-19 therapy, performance of randomised controlled blinded clinical trials became difficult. Results of sound clinical trials are eagerly awaited. We report a case of acute haemolysis leading to admission in intensive care unit and renal failure in a patient with uncovered G6PD deficiency. KEYWORDSCovid-19 hydroxychloroquine adverse event haemolysis glucose-6-phosphate dehydrogenase (G6PD) deficiency evidence-based medicine ARTICLE HISTORY

To assess the incidence, clinical, microbiological features and outcome of invasive Streptococcus agalactiae (GBS) infections in non-pregnant adults in three tertiary hospitals of the Brussels-Capital Region. All bacterial cultures positive for GBS, from 2005 to 2019 from 3 hospitals of the Brussels-Capital Region, were extracted, and only cases of invasive diseases were included. Medical files were retrospectively retrieved for risk factors, clinical manifestations and outcome and also antibiotic-susceptibility testing and GBS serotypes. Incidence rates were calculated based on the hospitals catchment populations. A total of 337 cases of GBS-invasive infections were included. The incidence of invasive GBS for the 3 hospitals increased from 3.7 to 8.2 cases per 100.000 inhabitants between 2009 and 2018 (p = 0.04). The most frequently identified risk factors were diabetes (36.8%), obesity (35.0%), cancer (21.7%), renal disease (20.8%), and advanced age (≥ 65 years; 47.2%). Isolated bacteremia (22%), osteoarticular infection (21.4%), abscesses (13.9%), and skin and soft tissue infections (18.4%) were the most frequent manifestations. Intensive care unit admission was required in 21.7% and overall mortality was 9.4%. All strains remained susceptible to penicillin over the years. Up to 20% of strains were resistant to clindamycin. Serotypes Ia, Ib, II, III, IV, and V represented 96.8% of the available serotypes (60/62). As reported in several countries, invasive GBS disease in non-pregnant adults represents an increasing burden, particularly among diabetic, obese, and elderly patients. Almost all serotypes identified are included in the upcoming hexavalent GBS conjugate vaccine.