Ampicillin-Sulbactam for Carbapenem-Susceptible Acinetobacter baumannii Pneumonia: A Case for High-Dose, Continuous Infusion Dosing Strategy in the Trauma ICU.

Background: The optimal ampicillin-sulbactam dosing regimen for carbapenem-susceptible Acinetobacter baumannii isolates in critically ill trauma patients has not been clearly defined. One strategy to provide the adequate sulbactam dose includes high-dose continuous infusion. Case(s) Description: We present three cases of critically ill trauma patients with augmented renal clearance treated with high-dose ampicillin-sulbactam through an intravenous continuous infusion for ventilator-associated pneumonia. All A. baumannii isolates were susceptible to sulbactam with low minimum inhibitory concentrations. All achieved clinical cure at the end of therapy and no recurrent pneumonia was noted. No clinically substantial adverse effect attributable to ampicillin-sulbactam therapy occurred. Discussion: There is limited evidence to endorse high-dose, continuous infusion ampicillin-sulbactam for treatment of infections caused by carbapenem-susceptible A. baumannii. This report presents three critically ill trauma patients with augmented renal clearance that achieved positive clinical outcomes with higher doses of ampicillin-sulbactam administered through a continuous infusion.

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.

Survey of venous thromboembolism prophylaxis in trauma patients: current prescribing practices and concordance with clinical practice guidelines.

Objectives: Pharmacological venous thromboembolism (VTE) prophylaxis is recommended in the vast majority of trauma patients. The purpose of this study was to characterize current dosing practices and timing of initiation of pharmacological VTE chemoprophylaxis at trauma centers. Methods: This was an international, cross-sectional survey of trauma providers. The survey was sponsored by the American Association for the Surgery of Trauma (AAST) and distributed to AAST members. The survey included 38 questions about practitioner demographics, experience, level and location of trauma center, and individual/site-specific practices regarding the dosing, selection, and timing of initiation of pharmacological VTE chemoprophylaxis in trauma patients. Results: One hundred eighteen trauma providers responded (estimated response rate 6.9%). Most respondents were at level 1 trauma centers (100/118; 84.7%) and had >10 years of experience (73/118; 61.9%). While multiple dosing regimens were used, the most common dose reported was enoxaparin 30 mg every 12 hours (80/118; 67.8%). The majority of respondents (88/118; 74.6%) indicated adjusting the dose in patients with obesity. Seventy-eight (66.1%) routinely use antifactor Xa levels to guide dosing. Respondents at academic institutions were more likely to use guideline-directed dosing (based on the Eastern Association of the Surgery of Trauma and the Western Trauma Association guidelines) of VTE chemoprophylaxis compared with those at non-academic centers (86.2% vs 62.5%; p=0.0158) and guideline-directed dosing was reported more often if the trauma team included a clinical pharmacist (88.2% vs 69.0%; p=0.0142). Wide variability in initial timing of VTE chemoprophylaxis after traumatic brain injury, solid organ injury, and spinal cord injuries was found. Conclusions: A high degree of variability exists in prescribing and monitoring practices for the prevention of VTE in trauma patients. Clinical pharmacists may be helpful on trauma teams to optimize dosing and increase prescribing of guideline-concordant VTE chemoprophylaxis.

Beta-lactam target attainment and associated outcomes in patients with bloodstream infections.

OBJECTIVES: To evaluate the association between early and cumulative beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) parameters and therapy outcomes in bloodstream infection (BSI). METHODS: Adult patients who received cefepime, meropenem, or piperacillin/tazobactam for BSI and had concentrations measured were included. Beta-lactam exposure was generated and the time that free concentration remained above the minimum inhibitory concentration (fT>MIC) and four multiples of MIC (fT>4 × MIC) were calculated for times 0-24 h and 0-7 days of therapy. Multiple regression analysis was performed to evaluate the impact of PK/PD on microbiological and clinical outcomes. RESULTS: A total of 204 patients and 213 BSI episodes were included. The mean age was 58 years and weight 83 kg. Age, Sequential Organ Failure Assessment (SOFA) score, haemodialysis, Pitt bacteraemia score, and hours of empiric antibiotic therapy were significantly associated with certain outcomes and retained in the final model. In multiple regression analysis, fT>4 × MIC at 0-24 h and 0-7 days was a significant predictor of negative blood culture on day 7 (P=0.0161 and 0.0068, respectively). In the time-to-event analysis, patients who achieved 100% fT>4 × MIC at 0-24 h and 0-7 days had a shorter time to negative blood culture compared with those who did not (log-rank P=0.0004 and 0.0014, respectively). No significant associations were identified between PK/PD parameters and other outcomes, including improvement in symptoms at day 7 and 30-day mortality. CONCLUSION: Early and cumulative achievement of fT>4 × MIC was a significant predictor of microbiological outcome in patients with BSI.

Risk Factors for Delirium and Association of Antipsychotic Use with Delirium Progression in Critically Ill Trauma Patients.

BACKGROUND: Delirium occurs frequently in critically ill and injured patients and is associated with significant morbidity and mortality. Limited data exists on the risk factors for developing delirium in critically ill trauma patients and the effect of antipsychotic (AP) medications on delirium progression. OBJECTIVE: The objective of this study is to determine the incidence of delirium in critically ill trauma versus non-trauma surgical patients and determine if the presence of trauma was associated with intensive care unit (ICU) delirium. Secondary outcomes included identifying risk factors for delirium and determining the impact of AP medication use on delirium progression in critically ill trauma patients. METHODS: This retrospective review studies adult trauma/surgical ICU patients admitted between May 2017-July 2018 to a level I trauma and tertiary referral center. Regression modeling was used to determine the impact of AP use on delirium-free days. RESULTS: Delirium was more common in critically ill trauma patients versus non-trauma surgical ICU patients [54/157 (34.4%) vs 42/270 (15.6%), P < .001]. Of the 54 trauma patients with delirium, 28 (52%) received an AP medication for delirium treatment and in the multiple linear regression analysis, AP use was significantly associated with fewer delirium-free days (P = .02). DISCUSSION: Higher admission sequential organ failure assessment scores and increased length of stay were significantly associated with delirium onset in critically ill trauma patients. Use of AP medications for delirium treatment in this population had a negative impact on delirium-free days.

Implementing a Discharge Opioid Bundle in Adult Trauma Patients Decreases the Amount of Opioids Prescribed at Discharge.

BACKGROUND: Opioids remain the mainstay treatment of acute pain caused by trauma. The lack of evidence driven prescribing creates a challenging situation for providers. We hypothesized that the implementation of a trauma discharge opioid bundle (TDOB) would decrease the total morphine milligram equivalents (MME) prescribed at discharge while maintaining pain control. METHODS: This was a pre-post study of adult trauma patients before and after implementation of a TDOB to guide the prescription of opioids and discharge prescription education in patients discharged from a level one trauma center. The pre-group and post-group, included consecutively discharged patients from September through November in 2018 and 2019. The primary outcome was the total MME prescribed at discharge. RESULTS: A total of 377 patients met inclusion criteria. One hundred and fifty-one patients were included in the pre-group and 226 in the post-group. The total MME prescribed at discharge (225 ± [150-300] pre vs 200 ± [100-225] post, P = < .001) and maximum MME/day (45 ± [30-45] vs 30 ± [20-45], P = .004) were significantly less in the post-group. Incidence of outpatient refills within fourteen days were similar. More non-opioid pain adjuncts were prescribed post-intervention and discharge pain education was provided more frequently. CONCLUSION: The implementation of a TDOB significantly reduced the MME prescribed at discharge without increasing the number of opioid refills.

Defining Pathogen and Susceptibility Patterns for Early Versus Late Ventilator Associated Pneumonia in Trauma Patients to Guide Empiric Treatment Decisions.

INTRODUCTION: Studies have demonstrated that trauma patients with early-ventilator associated pneumonia (early-VAP, < 7 days) have decreased risk of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa infections. We hypothesize that routinely using broad-spectrum antibiotics is unnecessary to treat trauma patients with the diagnosis of early-VAP. METHODS: This retrospective cohort study included adult trauma patients with the diagnosis of VAP. The primary outcome was the presence of MRSA and/or P. aeruginosa in patients with early- and late-VAP. Secondary outcomes included the bacterial susceptibility of pathogens to methicillin, ampicillin/sulbactam, ceftriaxone, piperacillin/tazobactam, and cefepime. Intensive care unit (ICU) and hospital length of stay (LOS), ventilator-free days, and in-hospital mortality were also collected. RESULTS: 164 patients met inclusion criteria, and 208 organisms (n = 90 early vs n = 118 late) were identified by respiratory culture. The incidence of MRSA and P. aeruginosa in early-VAP was 7.7% (7/90) and 5.6% (5/90), respectively. The susceptibility of bacteria causing early-VAP to ampicillin/sulbactam and ceftriaxone was 73.3% (66/90) and 83.3% (75/90), respectively. Ventilator-free days at 30 days was similar between groups (P = .649). Patients with late-VAP spent more time in the ICU (P = .040); however, in-hospital mortality was higher in the early-VAP group (P = .012). CONCLUSIONS: Ampicillin/sulbactam or ceftriaxone monotherapy did not provide reliable broad-spectrum coverage for early-VAP in our cohort. These findings highlight the importance of each institution performing a similar analysis to ensure adequate initial treatment of VAP.

Cefepime Daily Exposure and the Associated Impact on the Change in Sequential Organ Failure Assessment Scores and Vasopressors Requirement in Critically Ill Patients Using Repeated-Measures Mixed-Effect Modeling.

IMPORTANCE: Sepsis and septic shock are major healthcare problems that need early and appropriate management. OBJECTIVES: To evaluate the association of daily cefepime pharmacokinetic/pharmacodynamic (PK/PD) parameters with change in Sequential Organ Failure Assessment (SOFA) score and vasopressors requirement. DESIGN SETTING AND PARTICIPANTS: This is a retrospective study. Adult ICU patients who received cefepime for Gram-negative pneumonia or bloodstream infection (BSI) and had cefepime concentrations measured were included. Daily cefepime exposure was generated and PK/PD parameters calculated for patients. Repeated-measures mixed-effect modeling was used to evaluate the impact of PK/PD on the outcomes. MAIN OUTCOMES AND MEASURES: Change in daily SOFA score and vasopressors requirement. RESULTS: A total of 394 and 207 patients were included in the SOFA and vasopressors analyses, respectively. The mean (±sd) age was 55 years (19) and weight 81 kg (29). For the change in SOFA score, daily SOFA score, mechanical ventilation, renal replacement therapy, and number of vasopressors were included. In the vasopressors analysis, daily SOFA score, day of therapy, and hydrocortisone dose were significant covariates in the final model. Achieving cefepime concentrations above the minimum inhibitory concentration (MIC) (T>MIC) for 100% of the dosing interval was associated with 0.006 µg/kg/min decrease in norepinephrine-equivalent dose. Cefepime PK/PD did not have an impact on the daily change in SOFA score. CONCLUSIONS AND RELEVANCE: Achieving 100% T>MIC was associated with negligible decrease in vasopressors requirement in ICU patients with Gram-negative pneumonia and BSI. There was no impact on the change in SOFA score.

Neuroleptic Malignant Syndrome: A Potential Etiology of Multisystem Organ Failure in a Burn Patient.

Neuroleptic malignant syndrome (NMS) is described in the medical literature but rarely seen among acutely ill trauma patients. A 44-year-old man with burns to the hands and back after a chemical explosion was transported to an outside facility where he received treatment for presumed acute coronary syndrome after developing ventricular tachycardia and elevated serum troponins after the exposure. His cardiac catheterization was unremarkable, but an echocardiogram revealed severe cardiomyopathy, and he was also in multisystem organ failure. He was transferred to our facility after hospital day 2 for treatment of his multisystem organ failure and 2% total body surface area burns. His laboratory results were remarkable for a creatine kinase of >100 000 units/L, and he required 14 g of intravenous calcium. Upon further investigation, the patient reported taking ziprasidone for his bipolar disorder, and he had a core temperature of 103.5 °F on his initial presentation to the outside facility. As he convalesced, the unifying diagnosis was NMS. NMS is a side effect of antipsychotic therapy and is manifested by hyperpyrexia, rigidity, autonomic instability, and altered consciousness. An elevated creatine kinase >100 000 units/L is almost pathognomonic for NMS. Patients can also present with leukocytosis, organ failure, and electrolyte disturbances including hypocalcemia. We hypothesized that dehydration, the warm environmental conditions at our patient's job, and immense stress resulting in a catecholamine surge following his trauma were inciting triggers to this event. This case highlights the importance of considering alternate diagnoses in patients whose clinical presentation does not fit the most "obvious cause."

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.

Intraoperative liposomal bupivacaine for skin graft donor site analgesia: A retrospective cohort study.

INTRODUCTION: Burn injury and reconstructive operations often result in severe pain, particularly at skin graft donor sites. Traditional local anesthetics administered intraoperatively control pain at donor sites, but the duration of action is short. Liposomal bupivacaine, a novel local anesthetic, can provide sustained-release analgesia for 72h. The primary aim of this study was to describe the efficacy of liposomal bupivacaine for postoperative donor site pain control for patients undergoing skin graft procedures. METHODS: A retrospective cohort study was performed on patients who received a donor site liposomal bupivacaine field block and was compared to a matched control. Patients rated donor site pain on post-operative day 0 and 1, and stated whether the donor or graft site was more painful. RESULTS: Fifty-eight patients were included. Twenty-nine patients received liposomal bupivacaine. Eighty-six percent of patients in the treatment group rated donor site pain as three or less on postoperative day 0 and 1, compared to 3.4% in the control (p<0.0001). Also, 76% of patients in the treatment group stated donor site pain was less than graft site pain, compared to 3.4% in the control (p<0.0001). CONCLUSION: Patients who received liposomal bupivacaine reported less postoperative donor site pain and found the donor site to be less bothersome without major complications. Liposomal bupivacaine may be a safe and promising agent for prolonging postoperative analgesia and minimizing donor site pain.

Delineating the Role of Serum Immunoglobulin Titers in Burn Patients at High Risk for Herpes Simplex Virus Infection.

Herpes simplex virus (HSV) is common in the population and reactivation of latent infection often occurs in times of physiologic stress, including postburn injury. Active HSV infection complicates burn injury recovery and increases morbidity. A retrospective chart review of high-risk burn patients (≥20%TBSA and/or facial burns) who had screening HSV immunoglobulin titers drawn from 2015 to 2018 was conducted. Titer levels and morbidity-related outcomes were compared between patients who developed active infection and those who did not. Fifty-six patients had serum HSV titers measured. Twenty-nine patients (52%) developed clinical signs of HSV infection, almost all of which (97%) suffered facial burns. Titers were ordered on median hospital day 1.5 (0.00-4.0) and infection occurred on day 8.0 (2.0-16). Median HSV-1,2 IgM titers were significantly increased in patients who developed clinically active HSV infection (0.71 [0.44-1.1] vs 0.52 [0.34-0.74], P = .02). Median HSV-1 IgG (P = .65) and HSV-2 IgG titers (P = .97) were not different between groups. Patients who developed active infection had a comparable hospital length of stay (27 [9.5-40] days vs 20 [8.0-28] days, P = .17) and ICU length of stay (26 [13-49] days vs 19 [11-27] days, P = .09) to those who did not develop infection. There was no difference in mortality. Increased HSV-1 and 2 IgM screening levels were associated with an increased risk of developing active HSV infection, and offer a specific screening modality in high-risk patients. Elevated IgM titers warrant further consideration for administration of HSV prophylaxis, as earlier intervention may prevent infection onset and minimize morbidity.

Oral Administration of Injectable Ketamine During Burn Wound Dressing Changes.

Providing adequate analgesia during burn wound care is essential to patient-centered care. Both oral and intravenous (IV) ketamine are often used for analgesia and sedation. Ketamine may improve analgesia and decrease opioid requirements for burn wound care. Oral ketamine wafers and tablets have been used as a safe alternative internationally but are unavailable in the United States. The purpose of this study was to compare opioid usage and patient satisfaction scores in patients with and without the use of oral injectable ketamine for burn wound care, with each patient serving as their own control. Ketamine, opioid, and benzodiazepine dosages recorded during dressing changes were compared to dressing changes without ketamine use that occurred before and after ketamine-associated sessions in each patient. Fourteen patients received oral ketamine at a median (interquartile range [IQR]) dose of 2.5 (2.2-2.7) mg/kg. Ketamine use significantly decreased opioid requirements when compared to wound care sessions that did not use ketamine both before (50 [IQR: 30-75] mg vs 75 [IQR: 46-91] mg median IV morphine equivalents, P = .0097) and after (50 [IQR: 30-75] mg vs 63 [IQR: 50-96] mg median IV morphine equivalents, P = .0042) the ketamine-associated sessions. One patient experienced hallucinations, and no adverse events were observed. Hence, oral administration of injectable ketamine was associated with a decrease in opioid requirements during dressing changes. Additionally, ketamine use improved patient satisfaction (P = .0034). Preliminary data suggest this promising analgesia method is safe and effective for burn wound care.