Objective The aim of this study was to determine whether the current method of calculating a fosphenytoin reloading dose results in a therapeutic free phenytoin level on subsequent days. Methods Medical records of patients receiving fosphenytoin in the neurocritical care unit between July 2017 and June 2018 were screened. Included patients were those who had received at least three doses of fosphenytoin and required reloading doses according to concentrations obtained through therapeutic drug monitoring. Free phenytoin levels were categorized based on the prespecified patient-specific target range, generally between 1.5 and 2.5 mcg/mL. Results Of the fosphenytoin reloading doses administered, 48% (73/152) resulted in a therapeutic free phenytoin concentration on the subsequent day, with the remaining 52% resulting in nontherapeutic levels (39% subtherapeutic, 13% supratherapeutic). Our evaluation of reloading dose calculation strategies indicated that patients were two times as likely to obtain a therapeutic level when a modified pharmacokinetic equation omitting the use of volume of distribution or salt formulation was used (58%, n = 39) than they were with doses calculated using the current pharmacokinetic model (41%, n = 20) or doses based on provider preference (39%, n = 14).
ConclusionThe current method of calculating a fosphenytoin reloading dose in the critically ill population does not consistently result in therapeutic concentrations. With multiple factors affecting the pharmacokinetics of critically ill patients, the creation of a new pharmacokinetic model with less emphasis on volume of distribution may more consistently result in therapeutic concentrations.
Objectives
We evaluated the clinical characteristics and outcomes of patients with COVID-19 who received three-drug combination regimens for treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections during a single-centre outbreak. Our objective was to describe the clinical outcomes and molecular characteristics and in vitro synergy of antibiotics against CRAB isolates.
Materials and methods
Patients with severe COVID-19 admitted between April and July 2020 with CRAB infections were retrospectively evaluated. Clinical success was defined as resolution of signs/symptoms of infection without need for additional antibiotics. Representative isolates underwent whole-genome sequencing (WGS) and in vitro synergy of two- or three-drug combinations was assessed by checkerboard and time-kill assays, respectively.
Results
Eighteen patients with CRAB pneumonia or bacteraemia were included. Treatment regimens included high-dose ampicillin-sulbactam, meropenem, plus polymyxin B (SUL/MEM/PMB; 72%), SUL/PMB plus minocycline (MIN; 17%) or other combinations (12%). Clinical resolution was achieved in 50% of patients and 30-day mortality was 22% (4/18). Seven patients had recurrent infections, during which further antimicrobial resistance to SUL or PMB was not evident. PMB/SUL was the most active two-drug combination by checkerboard. Paired isolates collected before and after treatment with SUL/MEM/PMB did not demonstrate new gene mutations or differences in the activity of two- or three-drug combinations.
Conclusions
Use of three-drug regimens for severe CRAB infections among COVID-19 resulted in high rates of clinical response and low mortality relative to previous studies. The emergence of further antibiotic resistance was not detected phenotypically or through WGS analysis. Additional studies are needed to elucidate preferred antibiotic combinations linked to the molecular characteristics of infecting strains.
External urinary collection devices (ECDs) are increasingly used in female patients, however, their impact on bacteriuria and antimicrobial use is unclear. Comparing the periods before and after the implementation of an ECD use policy, we found an overall decrease in bacteriuria but no significant decrease in trend of monthly rates. Antimicrobial use for genitourinary indications did not change.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.