Hemostatic Efficacy and Safety of Weight-Based Versus Fixed-Dose 4F-PCC for Vitamin K Antagonist Reversal.

Background: Four-factor prothrombin complex concentrate (4F-PCC) is indicated for vitamin K antagonist (VKA) reversal but is associated with thrombotic events (TE). In 2018, the institution revised 4F-PCC dosing for VKA reversal from INR and weight-based dosing to a fixed-dose of 1500 units. Objective: The purpose of this study was to compare hemostatic efficacy and TE rate of fixed-dose 4PCC to weight-based dosing. Methods: This was a retrospective, single-center, quasi-experimental study of adult patients who received 4F-PCC for VKA reversal from January 2014 through May 2016 (INR and weight-based dosing) or April through October 2018 (fixed-dosing). The primary endpoint was hemostatic efficacy, defined by achieving an INR of ≤1.4, or an INR of ≤1.7 with evidence of hemostasis. The key secondary endpoint was TE within 14 days of 4F-PCC administration. Data were analyzed using descriptive statistics, chi-squared for nominal data and Mann-Whitney U for ordinal and continuous data. Results: The study included 163 patients who received weight-based dosing and 45 who received fixed-dose 4F-PCC. Hemostatic efficacy was 76.9% of patients in the weight-based group and 77.4% of patients in the fixed-dose group (P = .229). TE occurred in 13.5% of the weight-based vs 6.7% of the fixed-dose group (P = .181). Conclusion: This study found no difference in hemostatic efficacy with fixed-dose 4F-PCC for VKA reversal compared to INR and weight-based dosing. The occurrence of TE was reduced by 50% with the 4F-PCC fixed-dose strategy; however, this difference was not statistically significant. Further randomized studies are needed to confirm these results.

An Appraisal of Pharmacotherapy-Pertinent Literature Published in 2021 and 2022 for Clinicians Caring for Patients With Thermal or Inhalation Injury.

Studies focusing on pharmacotherapy interventions to aid patients after thermal injury are a minor focus in burn injury-centered studies and published across a wide array of journals, which challenges those with limited resources to keep their knowledge current. This review is a renewal of previous years' work to facilitate extraction and review of the most recent pharmacotherapy-centric studies in patients with thermal and inhalation injury. Twenty-three geographically dispersed, board-certified pharmacists participated in the review. A Medical Subject Heading-based, filtered search returned 2336 manuscripts over the previous 2-year period. After manual review, 98 (4%) manuscripts were determined to have a potential impact on current pharmacotherapy practice. The top 10 scored manuscripts are discussed. Only 17% of those reviewed were assessed to likely have little effect on current practice. The overall impact of the current cohort was higher than previous editions of this review, which is encouraging. There remains a need for investment in well-designed, high-impact, pharmacotherapy-pertinent research for patients sustaining thermal or inhalation injuries.

When More Is Still Not Enough: A Case of Ceftazidime-Avibactam Resistance in a Burn Patient.

Burn patients have numerous risk factors for multidrug-resistant organisms (MDROs) and altered pharmacokinetics, which both independently increase the risk of treatment failure. Data on appropriate antimicrobial dosing are limited in this population and therapeutic drug monitoring (TDM) for beta-lactams is impractical at most facilities. Technology is available that can detect genetic markers of resistance, but they are not all encompassing, and often require specialized facilities that can detect less common genetic markers. Newer antimicrobials can help combat MDROs, but additional resistance patterns may evolve during treatment. Considering drug shortages and antimicrobial formularies, clinicians must remain vigilant when treating infections. This case report describes the development of resistance to ceftazidime-avibactam in a burn patient. The patient was a 54-year-old burn victim with a 58% total body surface area (TBSA) thermal burn who underwent multiple courses of antibiotics for various Pseudomonal infections. The initial Pseudomonal wound infection was sensitive to cefepime, aminoglycosides, and meropenem. A subsequent resistant pseudomonal pneumonia was treated with ceftazidime-avibactam 2.5 g every 6 hours due to the elevated MIC to cefepime (16 mcg/mL) and meropenem (>8 mcg/mL). Although the patient improved over 7 days, the patient again spiked fevers and had increased white blood counts (WBC). Repeat blood cultures demonstrated a multidrug-resistant (MDR) Pseudomonas with a minimum inhibitory concentration (MIC) to ceftazidime-avibactam of 16 mcg/mL, which is above the Clinical and Laboratory Standards Institute (CLSI) breakpoint of 8 mcg/mL. At first, resistance was thought to have occurred due to inadequate dosing, but genetic work demonstrated multiple genes encoding beta-lactamases.

A Cautionary Tale of Etanercept Use in Patients With Toxic Epidermal Necrolysis.

Toxic epidermal necrolysis (TEN) is a severe cutaneous reaction that can be life-threatening. In the United States, there are no established guidelines for the treatment of TEN. Supportive care including fluids and supportive therapies are the current recommendations. Research surrounding TEN involves mostly case studies or small, uncontrolled studies. Recent literature describes the use of tumor necrosis factor blockers in the treatment of TEN with positive results. These case reports describe decreased time to reepithelization, hospital length of stay, and minimal side effects. Conversely, we present three fatalities after the administration of etanercept.

Impact of inappropriate initial antibiotics in critically ill surgical patients with bacteremia.

BACKGROUND: Bloodstream infections in critically ill patients are associated with mortality as high as 60% and a prolonged hospital stay. We evaluated the impact of inappropriate antibiotic therapy (IAAT) in a critically ill surgical cohort with bacteremia. METHODS: This retrospective study evaluated adults with intensive care unit admission greater than 72 hours and bacteremia. Two groups were evaluated: appropriate antibiotic therapy (AAT) vs IAAT. RESULTS: In 72 episodes of bacteremia, 57 (79%) AAT and 15 (21%) IAAT, mean age was 54 ± 17 years and APACHE II of 17 ± 8. Time to appropriate antibiotics was longer for IAAT (3 ± 5 IAAT vs 1 ± 1 AAT days, P = .003). IAAT was seen primarily with Acinetobacter spp (33% IAAT vs 9% AAT, P = .01) and Enterococcus faecium (26% IAAT vs 7% AAT, P = .03). If 2 or more bacteremic episodes occurred, Acinetobacter spp. was more likely, 32% vs 2%, P = .001. CONCLUSIONS: AAT selection is imperative in critically patients with bacteremia to reduce the significant impact of inappropriate selection. Repeated episodes of bacteremia should receive special attention.

Pharmacokinetics and pharmacodynamics of antibacterial and antifungal agents in adult patients with thermal injury: a review of current literature.

Patients with significant thermal injury are at a high risk for developing bacterial and fungal infections due to the loss of protective integument and often require lengthy treatment courses with anti-infective agents. Dosing of these agents in the burn population is challenging as these patients experience changes in their physiology around 48 hours postinjury. These changes include increased cardiac output, increased blood flow to the kidneys and liver, and decreased albumin production. These alterations in the physiology can lead to an increased drug clearance, higher volumes of distribution, and increased or decreased total drug exposure. Currently, there are no guidelines describing the most ideal method of dosing anti-infectives in this population, and most studies that have been published include only a small number of patients. The purpose of this review is to summarize the existing literature regarding the pharmacokinetics and pharmacodynamics of antibiotics and antifungal agents in the burn population and to provide dosing suggestions whenever possible. Not all antibiotics and antifungal agents have been studied, and further research is needed in this area in order to provide optimal care for patients with thermal injury.

Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Pneumonia with Ceftaroline Fosamil in a Patient with Inhalational Thermal Injury.

A 48-year-old female, who was found unresponsive and suffered inhalation injury secondary to a house fire, was transferred to our burn center for definitive treatment. Post tracheostomy, the patient became febrile and tachycardic. On hospital day (HD) 5, the patient expressed thick yellow secretions during suctioning and diffuse rhonchi was noted on physical exam. Blood cultures and a culture from the broncheo-alvelolar lavage grew Gram-positive cocci in clusters and the patient was started on empiric vancomycin. Despite aggressive vancomycin dosing (1750 mg intravenously every 6 h), the patient's status continued to deteriorate. The organism was identified as methicillin-resistant Staphylococcus aureus (MRSA) with a vancomycin minimum inhibitory concentration (MIC) of 2 mg/L. Based on the potential for drug-drug interactions with linezolid, the patient was started on ceftaroline fosamil (MIC = 0.5 mg/L) 600 mg intravenously every 8 h with a prolonged 2-h infusion to anticipate suboptimal concentrations secondary to thermal burn injury. Post change in antibiotic therapy, a rapid clinical improvement was observed with the patient becoming afebrile at 48 h after initiation of ceftaroline. The patient completed a total of 14 days of ceftaroline therapy and was subsequently weaned from the ventilator on HD 22 and decannulated 2 days later. To our knowledge, this is the first report of the use of ceftaroline for the treatment of MRSA pneumonia in a patient with thermal injury.

Extensive toxic epidermal necrolysis versus acute graft versus host disease after allogenic hematopoietic stem-cell transplantation: challenges in diagnosis and management.

Toxic epidermal necrolysis (TEN) is a rare complication after allogeneic hematopoietic stem-cell transplantation and carries high mortality rates. Graft-vs-host disease (GVHD) is also a life-threatening complication, and potentially indistinguishable from TEN because of similar clinical symptoms. However, current therapeutic recommendations differ between these two conditions, thereby posing a diagnostic dilemma. The authors, herein, present a complicated postoperative course after bone marrow transplantation with concurrent gastrointestinal and hepatic GVHD, and extensive epidermolytic disease compatible with both severe cutaneous GVHD and TEN. An early consult to a specialized burn service, and prompt transfer to a burn intensive care unit with extensive supportive care and nursing are of paramount importance in the management of immunosuppressed patients with TEN. Better understanding of the pathogenesis of TEN and GVHD after hematopoietic stem-cell transplantation, further treatment strategies, and more advanced diagnostic techniques are still needed to achieve acceptable mortality rates.