Sepsis, a life-threatening organ dysfunction caused by a dysregulated response to infection is a major public health concern, as it is a leading cause of mortality and critical illness worldwide. ...Antibiotics are one of the cornerstones of the treatment of sepsis; administering appropriate antibiotics in a rapid fashion to obtain adequate drug concentrations at the site of the infection can improve survival of patients. Nevertheless, it is a challenge for clinicians to do so. Indeed, clinicians today are regularly confronted with infections due to very resistant pathogens, and standard dosage regimens of antibiotics often do not provide adequate antibiotic concentrations at the site of the infection. We provide a narrative minireview of different anti-infectious treatments currently available and suggestions on how to deliver optimized dosage regimens to septic patients. Particular emphasis will be made on newly available anti-infectious therapies.
A 30-year-old bombing victim with a fracture-related pandrug-resistant Klebsiella pneumoniae infection after long-term (>700 days) antibiotic therapy is treated with a pre-adapted bacteriophage along ...with meropenem and colistin, followed by ceftazidime/avibactam. This salvage therapy results in objective clinical, microbiological and radiological improvement of the patient's wounds and overall condition. In support, the bacteriophage and antibiotic combination is highly effective against the patient's K. pneumoniae strain in vitro, in 7-day mature biofilms and in suspensions.
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.
Highlights • Obesity is likely to cause alterations to antimicrobial pharmacokinetics (PK). • Hydrophilic antimicrobials may display altered PK in obese critically ill patients. • Loading doses of ...vancomycin should be based on total body weight in obese patients. • In most studies standard dosage regimens of antimicrobials are sufficient to achieve pharmacodynamic targets. • Larger antimicrobial doses may be required for pathogens with higher MICs.
Belgium has actively participated in clinical research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since the beginning of the pandemic to help identify effective and safe ...treatments for COVID-19. The objective of this review is to provide a picture of the clinical studies carried out in hospitalized patients with COVID-19 in Belgium. We collected data on all randomized, interventional trials in patients with COVID-19 that were registered on two recognized clinical trial registers, started enrollment before 31 December 2021, and included at least one patient in a Belgian center. Data were collected concerning the therapies investigated and the nature of the trials performed. Thirty-three hospitals (32% of all Belgian hospitals) participated in at least one of 28 trials (13 sponsored by the industry and 15 by academic centers) on therapeutics for COVID-19 in hospitalized patients: 7 (25%) evaluated antivirals, 17 (61%) immunomodulators, 2 (7%) anti-coagulants, and 1 (3%) nitric oxide to improve respiratory function. Nineteen (68%) were phase II trials. Only three (11%) of the trials were international platform trials. Despite numerous trials, less than 3% of all Belgian patients hospitalized with COVID-19 participated in a clinical trial on therapeutics. As in many other countries, more efforts could have been made to avoid running small, under-powered, mono- or bicenter trials, to create better collaboration between the different Belgian hospitals, and to participate in more international clinical trials, and more specifically in adaptive, platform trials.
Difficult-to-treat pulmonary infections caused by multidrug-resistant (MDR) pathogens are of great concern because their incidence continues to increase worldwide and they are associated with high ...morbidity and mortality. Nebulized antibiotics are increasingly being used in this context. The advantages of the administration of a nebulized antibiotic in respiratory tract infections due to MDR include the potential to deliver higher drug concentrations to the site of infection, thus minimizing the systemic adverse effects observed with the use of parenteral or oral antibiotic agents. However, there is an inconsistency between the large amount of experimental evidence supporting the administration of nebulized antibiotics and the paucity of clinical studies confirming the efficacy and safety of these drugs. In this narrative review, we describe the current evidence on the use of nebulized antibiotics for the treatment of severe respiratory infections.
•The majority of hospitalized COVID-19 patients are zinc deficient.•There is a weak correlation between plasma zinc and the length of hospital stay.•cHIS score, described by Webb et al., is ...externally validated in this study.•Current findings do not support plasma zinc as a robust prognostic factor.
Zinc deficiency is associated with impaired antiviral response, cytokine releasing syndrome (CRS), and acute respiratory distress syndrome. Notably, similar complications are being observed during severe SARS-CoV-2 infection.
We conducted a prospective, single-center, observational study in a tertiary university hospital (CUB-Hôpital Erasme, Brussels) to address the zinc status, the association between the plasma zinc concentration, development of CRS, and the clinical outcomes in PCR-confirmed and hospitalized COVID-19 patients.
One hundred and thirty-nine eligible patients were included between May 2020 and November 2020 (median age of 65 years IQR = 54, 77).
Our cohort's median plasma zinc concentration was 57 µg/dL (interquartile range IQR = 45, 67) compared to 74 µg/dL (IQR = 64, 84) in the retrospective non-COVID-19 control group (N = 1513; p < 0.001). Markedly, the absolute majority of COVID-19 patients (96%) were zinc deficient (<80 µg/dL).
The median zinc concentration was lower in patients with CRS compared to those without CRS (-5 µg/dL; 95% CI = -10.5, 0.051; p = 0.048).
Among the tested outcomes, zinc concentration is significantly correlated with only the length of hospital stay (rho = -0.19; p = 0.022), but not with mortality or morbidity. As such, our findings do not support the role of zinc as a robust prognostic marker among hospitalized COVID-19 patients who in our cohort presented a high prevalence of zinc deficiency. It might be more beneficial to explore the role of zinc as a biomarker for assessing the risk of developing a tissue-damaging CRS and predicting outcomes in patients diagnosed with COVID-19 at the early stage of the disease.
Obesity is a significant global public health concern that is associated with an elevated risk of comorbidities as well as severe postoperative and nosocomial infections. The treatment of infections ...in critically ill obese patients can be challenging because obesity affects the pharmacokinetics and pharmacodynamics of antibiotics, leading to an increased risk of antibiotic therapy failure and toxicity due to inappropriate dosages. Precision dosing of antibiotics using therapeutic drug monitoring may help to improve the management of this patient population. This narrative review outlines the pharmacokinetic and pharmacodynamic changes that result from obesity and provides a comprehensive critical review of the current available data on dosage adjustment of antibiotics in critically ill obese patients.
There is currently an increase in the emergence of multidrug-resistant bacteria (MDR) worldwide, requiring the development of novel antibiotics. However, it is not only the choice of antibiotic that ...is important in treating an infection; the drug regimen also deserves special attention to avoid underdosing and excessive concentrations. Critically ill patients often have marked variation in renal function, ranging from augmented renal clearance (ARC), defined as a measured creatinine clearance (CrCL) ≥ 130 mL/min*1.73 m
, to acute kidney injury (AKI), eventually requiring renal replacement therapy (RRT), which can affect antibiotic exposure. All novel beta-lactam (BLs) and/or beta-lactam/beta-lactamases inhibitors (BL/BLIs) antibiotics have specific pharmacokinetic properties, such as hydrophilicity, low plasma-protein binding, small volume of distribution, low molecular weight, and predominant renal clearance, which require adaptation of dosage regimens in the presence of abnormal renal function or RRT. However, there are limited data on the topic. The aim of this review was therefore to summarize available PK studies on these novel antibiotics performed in patients with ARC or AKI, or requiring RRT, in order to provide a practical approach to guide clinicians in the choice of the best dosage regimens in critically ill patients.
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