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.

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.

Vitamin D Deficiency Is Associated With Increased Length of Stay After Acute Burn Injury: A Multicenter Analysis.

In burn patients, vitamin D deficiency has been associated with increased incidence of sepsis and infectious complications. The objective of this study was to assess the impact of vitamin D deficiency in adult burn patients on hospital length of stay (LOS). This was a multicenter retrospective study of adult patients at 7 burn centers admitted over a 3.5-year period, who had a 25-hydroxyvitamin D concentration drawn within the first 7 days of injury. Of 1147 patients screened, 412 were included. Fifty-seven percent were vitamin D deficient. Patients with vitamin D deficiency had longer LOS (18.0 vs 12.0 days, P < .001), acute kidney injury (AKI) requiring renal replacement therapy (7.3 vs 1.7%, P = .009), more days requiring vasopressors (mean 1.24 vs 0.58 days, P = .008), and fewer ventilator-free days of the first 28 days (mean 22.9 vs 25.1, P < .001). Univariable analysis identified burn center, AKI, TBSA, inhalation injury, admission concentration, days until concentration drawn, days until initiating supplementation, and dose as significantly associated with LOS. After controlling for center, TBSA, age, and inhalation injury, vitamin D deficiency was associated with longer LOS. In conclusion, patients with thermal injuries and vitamin D deficiency on admission have increased LOS and worsened clinical outcomes when compared with patients with nondeficient vitamin D concentrations.

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.

A multicenter study analyzing the association of vitamin D deficiency and replacement with infectious outcomes in patients with burn injuries.

Vitamin D (25OHD) deficiency is associated with poor outcomes in intensive care populations. The primary objective of this 7-center study was to determine if 25OHD deficiency is associated with infectious outcomes in adult burn patients. Generalized linear mixed modeling was used to control for center effect, percent total body surface area burn (% TBSA), age, and presence of inhalation injury. A total of 1147 patients were initially included (admitted January 2016 through August 2019). After exclusions, 234 (56.8%) in the deficient (25OHD<20 ng/mL) and 178 in the non-deficient group (25OHD ≥ 20 ng/mL) remained, surpassing a priori power requirements. The non-deficient group had their concentration drawn earlier (p < 0.001), were more likely to be male (p = 0.006), Caucasian (p < 0.001), have lower body mass index (p = 0.009), lower % TBSA (p = 0.002), and taking a 25OHD supplement prior to admission (p < 0.001). Deficient patients were more likely to have an infectious outcome (52.1% vs 36.0%, p = 0.002), acute kidney injury with renal replacement therapy (p = 0.009), less ventilator free days in the first 28 days (p < 0.001), and vasopressors (p = 0.01). After controlling for center, % TBSA, age, and inhalation injury the best model also included presence of deficiency (OR 2.425 [CI 1.206-4.876]), days until 25OHD supplement initiation (OR 1.139 [CI 1.035-1.252]), and choice of cholecalciferol over ergocalciferol (OR 2.112 [CI 1.151-3.877]). To the authors' knowledge, this is the first multicenter study to evaluate the relationship between 25OHD and infectious complications in burn patients.

ABC's of Vitamin Supplementation in Critical Illness.

Critical illness commonly presents as a systemic inflammatory process. Through this inflammation, there is an enhanced production of reactive oxygen and nitrogen species combined with marked reductions in protective plasma antioxidant concentrations. This imbalance is referred to as oxidative stress and is commonly encountered in numerous disease states in the critically ill including sepsis, trauma, acute respiratory distress syndrome, and burns. Oxidative stress can lead to cellular, tissue and organ damage as well as increased morbidity and mortality in critically ill patients. Supplementation with exogenous micronutrients to restore balance and antioxidant concentrations in critically ill patients has been considered for several decades. It is proposed that antioxidant vitamins, such as vitamins A and C, may minimize oxidative stress and improve clinical outcomes. Vitamin B formulations may play a role in curtailing lactic acidosis and are recently being evaluated as an acute phase reactant. However, few large, randomized trials specifically investigating the role of vitamin supplementation in the critically ill patient population are available. This article seeks to review recently published literature surrounding the role of supplementation of vitamins A, B and C in critically ill patients.

A Review of the Most Impactful Published Pharmacotherapy-Pertinent Literature of 2017 and 2018 for Clinicians Caring for Patients with Burn or Inhalation Injuries.

Staying current and evaluating literature related to pharmacotherapy in burn or inhalation injury can be difficult as burn care teams are multidisciplinary and pertinent content can be spread across a plethora of journals. The goal of this review is to critically evaluate recently published pharmacotherapy-pertinent literature, assist practitioners staying current, and better identify potential future research targets. Twelve board-certified clinical pharmacists with experience caring for patients with burn and inhalation injuries reviewed and graded scientific literature published in 2017 and 2018. An MeSH-based search revealed 1158 articles related to burns, which were published during the 2-year period. One-hundred fifty one were determined to be potentially related to pharmacotherapy. After exclusions, only 82 (7%) remained for scoring, and the top 10 comprehensively presented. More than half of the reviewed manuscripts were assessed as lacking a significant impact on pharmacotherapy. There is a need for higher impact literature to support pharmacotherapy-pertinent treatment of such complex patients.

Isolation and structure determination of malevamide E, a dolastatin 14 analogue, from the marine cyanobacterium Symploca laete-viridis.

A new depsipeptide, malevamide E (1), was isolated from field-collected colonies of the filamentous cyanobacterium Symploca laete-viridis. The gross structure of 1 was determined by spectroscopic analyses, including one- and two-dimensional NMR and accurately measured MS/MS. Chiral HPLC analyses of an acid hydrolysate of 1 allowed the stereochemical assignments of its amino acid residues, which include N-methyl-L-alanine, alpha-N,gamma-N-dimethyl-L-asparagine, N-methyl-L-phenylalanine, L-proline, D-valine, and N-methyl-L-valine. LC-MS/MS analysis of S. laete-viridis fractions established the co-occurrence of malevamide E (1) and its homologue dolastatin 14 (2), which was previously reported in low yield from the sea hare Dolabella auricularia. Malevamide E (1) demonstrated a dose-dependent (2-45 microM) inhibition of store-operated Ca(2+) entry in thapsigargin-treated human embryonic kidney (HEK) cells, indicating an inhibitory effect on Ca(2+) release-activated Ca(2+) (CRAC) channels.