A Multicenter, Retrospective Outcome Analysis of Vancomycin Area Under the Curve versus Trough-Based Dosing Strategies in Patients with Burn OR Inhalational Injuries (MONITOR).

Vancomycin is a glycopeptide antibiotic that requires close therapeutic monitoring. Prolonged exposure to elevated concentrations increases risk for serious adverse effects such as nephrotoxicity. However, sub-therapeutic concentrations may lead to bacterial resistance and clinical failure or death. The most recent Infectious Diseases Society of America (IDSA) publication regarding therapeutic monitoring of vancomycin recommends utilizing area under the curve (AUC)-based monitoring to maximize clinical success. Despite the guideline recommendation for AUC-guided dosing, many institutions still use trough-only monitoring in their practices, including those caring for patients with acute burn injuries. Following burn injury, patients are at a higher risk for infections, multi-organ failure, and pharmacokinetic alterations. The primary objective of this multi-center retrospective study is to determine optimal therapeutic monitoring of vancomycin by comparing clinical success between AUC vs. trough-based monitoring in burn patients. MONITOR was a multicenter, retrospective study of patients with thermal or inhalation injury admitted to one of 13 burn centers from 1/1/17 to 8/31/22 who received vancomycin. Demographic and clinical course data, including acute kidney injury (AKI) incidence and clinical success were obtained. Patients were evaluated for clinical success and grouped according to method of monitoring and adjusting doses: AUC vs. trough-based monitoring. Clinical success was a composite definition and lack of meeting any 1 of 5 criteria: 1) persistent infection, 2) relapse, 3) antibiotic failure (clinical worsening), 4) AKI, 5) death. Five-hundred seventeen vancomycin courses were assessed from 485 patients. There was no difference in the rate of clinical success between AUC monitored and the trough-only monitored groups. Incidence of AKI was higher in the trough-only group; however, was not statistically significant after controlling for renal function on admission, past medical history of chronic kidney disease (CKD), and concomitant nephrotoxins.

Precision Medicine Approach Using Triple Combination Antifungal Therapy for Fusarium Brain Abscesses and Endocarditis in an Adult Burn Patient.

We report a management strategy for disseminated Fusarium solani fungal infection in an adult 35% total body surface area burn patient with brain abscesses and concomitant pulmonic valve endocarditis resulting in the longest survival reported in a burn patient. Early in his hospital course, the patient was diagnosed with a Fusarium burn wound infection with concomitant fungemia and was treated with a prolonged course of intravenous (IV) antifungal monotherapy. Shortly thereafter, he developed focal neurologic deficits and was found to have brain abscesses on MRI. He underwent emergent craniotomy with debridement, and triple antifungal therapy was initiated. Transesophageal echocardiography demonstrated pulmonic valve vegetations, which resolved with triple antifungal therapy. Disseminated Fusarium solani infection is quite rare with mortality approaching 100%. Given the rarity of this disease process, there are no established antifungal treatment guidelines. However, this patient survived for approximately 1 year after diagnosis with treatment including source control via craniotomy and debridement coupled with prolonged courses of combination antifungal therapy (given the near pan-resistance of his fungal infection). Pharmacogenomic testing was utilized to establish the patient's metabolism of voriconazole and dosing adjusted accordingly to improve the efficacy of the combination therapy. To our knowledge, an adult burn patient surviving this length of time after Fusarium brain abscesses with disseminated infection has not been previously described.

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.

Experience with Implementing a Beta-lactam Therapeutic Drug Monitoring Service in a Burn Intensive Care Unit: A Retrospective Chart Review.

Thermal injuries alter pharmacokinetics, complicating the prediction of standard antibiotic dose effectiveness. Therapeutic drug monitoring (TDM) has been proposed to prevent subtherapeutic dosing of antibiotic therapy, but remains scarcely studied in the burn patient population. A retrospective chart review of burn patients receiving beta-lactam TDM from 2016 to 2019 was conducted. Adult patients with thermal injury receiving cefepime, piperacillin/tazobactam, or meropenem for ≥48 hours were included. Between February 2016 and July 2017, we utilized selective TDM based on clinical judgement to guide treatment. From October 2018 until July 2019, TDM was expanded to all burn patients on beta-lactams. The primary endpoint was achievement of therapeutic concentration, and the secondary endpoints were clinical cure, culture clearance, new resistance, length of stay, and mortality. The selective (control) group included 19 patients and the universal (study) group reviewed 23 patients. In both groups, skin and lungs were the most common primary infection sources, with Pseudomonas aeruginosa as the most common species. In the universal cohort, patients were older with higher risk factors, but more frequently achieved the target drug concentration, required less days to start TDM (p < .0001), and had more frequent measurements and beta-lactam dose adjustments. Positive clinical outcome was reported in 77%, and microbial eradication in 82% of all patients. All clinical outcomes were similar between the groups. The implementation of beta-lactam TDM protocol shortened the time, increased the probability of appropriate target attainment, and individualized beta-lactam therapy in burn patients.

A Review of the Most Impactful Published Pharmacotherapy-Pertinent Literature of 2019 and 2020 for Clinicians Caring for Patients With Thermal or Inhalation Injury.

Keeping abreast with current literature can be challenging, especially for practitioners caring for patients sustaining thermal or inhalation injury. Practitioners caring for patients with thermal injuries publish in a wide variety of journals, which further increases the complexity for those with resource limitations. Pharmacotherapy research continues to be a minority focus in primary literature. 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. Sixteen geographically dispersed, board-certified pharmacists participated in the review. A MeSH-based, filtered search returned 1536 manuscripts over the previous 2-year period. After manual review and exclusions, only 98 (6.4%) manuscripts were determined to have a potential impact on current pharmacotherapy practices and included in the review. A summary of the 10 articles that scored highest are included in the review. Nearly half of the reviewed manuscripts were assessed to lack a significant impact on current practice. Despite an increase in published literature over the previous 2-year review, the focus and quality remain unchanged. There remains a need for investment in well-designed, high impact, pharmacotherapy-pertinent research for patients sustaining thermal or inhalation injuries.