Intravenous fosfomycin for the treatment of multidrug-resistant pathogens: what is the evidence on dosing regimens?

Introduction: The intravenous (IV) formulation of fosfomycin has been re-introduced in clinical practice mainly to overcome treatment failures against multidrug-resistant (MDR) bacteria. Appropriate dosing schedules of the IV formulation have not yet been established.

Areas covered: The mechanism of action and resistance development, commercial IV formulations, pharmacokinetic/pharmacodynamic (PK/PD) properties, IV dosing regimens for the treatment of MDR infections along with efficacy and safety issues were reviewed. Data regarding specific MDR pathogens, daily doses and patients’ outcomes, gaps in the current literature, and in progress research agenda are presented.

Expert opinion: The doses of fosfomycin IV range between 12 and 24 grams/day depending on the severity of infection. The efficacy and safety of the commonly administered doses have been shown mainly in observational non-comparative trials. The optimal dose ensuring maximal efficacy with minimal toxicity along with the most appropriate co-administered antibiotic(s) need further evaluation. The pharmacokinetic/pharmacodynamic parameter associated with maximum efficacy has not yet been established, although, the ratio of the area under the concentration-time curve (AUC) for the free unbound fraction of fosfomycin versus the MIC (fAUC/MIC) may be linked to optimal treatment. RCTs and other comparative studies are underway to address gaps of knowledge in adult patients and neonates.     

Epidemiology and diagnosis of pulmonary embolism in lung cancer patients: is there a role for age adjusted D-dimers cutoff?

Journal of Thrombosis and Thrombolysis - Our knowledge about the incidence of pulmonary embolism (PE) and the performance of age adjusted D-dimers (Dd) cutoff amongst patients with lung cancer (LC)...     

Thromboembolic risk and anticoagulant therapy in COVID-19 patients: emerging evidence and call for action

Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated with coagulopathy, namely disseminated intravascular coagulation, which has a rather prothrombotic character with high risk of venous thromboembolism. The incidence of venous thromboembolism among COVID-19 patients in intensive care units appears to be somewhat higher compared to that reported in other studies including such patients with other disease conditions. D-dimer might help in early recognition of these high-risk patients and also predict outcome. Preliminary data show that in patients with severe COVID-19, anticoagulant therapy appears to be associated with lower mortality in the subpopulation meeting sepsis-induced coagulopathy criteria or with markedly elevated d-dimer. Recent recommendations suggest that all hospitalized COVID-19 patients should receive thromboprophylaxis, or full therapeutic-intensity anticoagulation if such an indication is present.     

A state of the art review on optimal practices to prevent,recognize, and manage complications associated with intravascular devices in the critically ill

Intravascular catheters are inserted into almost all critically ill patients. This review provides up-to-date insight into available knowledge on epidemiology and diagnosis of complications of central vein and arterial catheters in ICU. It discusses the optimal therapy of catheter-related infections and thrombosis. Prevention of complications is a multidisciplinary task that combines both improvement of the process of care and introduction of new technologies. We emphasize the main component of the prevention strategies that should be used in critical care and propose areas of future investigation in this field.     

The mechanical performance and histomorphological structure of the descending aorta in hyperthyroidism

Thyroid hormones decrease systemic vascular resistance by directly affecting vascular smooth muscle relaxation. There is limited literature about their effect on the mechanical performance of the aortic wall. Therefore, the authors determined the influence of hyperthyroidism on the mechanical properties and histomorphological structure of the descending thoracic aorta in rats. Severe hyperthyroidism was induced in 20 male Wistar rats by administering L-thyroxine (T(4)) in their drinking water for 8 weeks; age-matched normal euthyroid rats acted as controls. Animals were sacrificed, and the mechanical and histomorphometrical characteristics of the descending thoracic aorta were studied. The aortic wall of hyperthyroid rats was stiffer than that of euthyroid animals at the upper physiologic levels of stress or strain (p < 0.05) but less stiff at the lower physiologic and lower levels (p < 0.05). The aorta of hyperthyroid animals compared with that of euthyroid ones showed an increase of the internal and external diameters (p < 0.05), the media area (p < 0.05), the number of smooth muscle cell nuclei (p < 0.05), and the collagen density (p < 0.05) and a decrease in the elastin laminae thickness (p < 0.001) and elastin density (p < 0.001). In hyperthyroid rats, the aortic wall was stiffer at the upper physiologic and higher levels of stress and strain. These changes correlated with microstructural changes of the aortic wall. The coexistence of hyperthyroidism with disease states or clinical conditions that predispose to increased arterial pressure may be associated with increased arterial stiffness and have undesirable consequences on the mechanical performance of the thoracic aorta and hemodynamic homeostasis. These changes could lead to an increased risk for developing vascular complications.     

Colonization and infection by colistin-resistant Gram-negative bacteria in a cohort of critically ill patients

In recent years there has been renewed interest in colistin for the treatment of infections by multidrug-resistant Gram-negative bacteria, causing concern that increasing use may be accompanied by the emergence of resistance. This is a retrospective cohort study of colonization and infection by colistin-resistant (CR) gram-negative bacteria in critically ill patients. Colonization data were based on surveillance culture results. Among 150 patients, 78 (52%) were colonized by CR Gram-negative bacteria. Among them, 30 (20%) were colonized by Klebsiella pneumoniae isolates and 51 (34%) were colonized by intrinsically resistant to colistin (CIR) enterobacteriaceae. Seven cases of infection were caused by CR K. pneumoniae and 12 cases by CIR strains. The main risk factor for colonization by CR pathogens was colistin treatment.