Evolution and Transmission of Cefiderocol-Resistant Acinetobacter baumannii During an Outbreak in the Burn Intensive Care Unit.

We report on 11 critically ill burn patients treated with cefiderocol for carbapenem-resistant Acinetobacter baumannii infections. Clinical success was achieved in 36% and complicated by treatment-emergent resistance and interpatient transmission of cefiderocol-resistant A. baumannii. Resistant isolates harbored disrupted pirA and piuA genes that were not disrupted among susceptible isolates.

Evaluation of Hospitalized Patient Outcomes in COVID-19 Infection for Continued versus Discontinued Use of Preadmission Antiplatelet Regimen.

ObjectiveIn SARS-CoV-2 (COVID-19) infection, it is unclear if continuation of preadmission antiplatelet regimens upon hospitalization will improve hypercoagulability outcomes. Methods: This retrospective cohort study analyzed adult patients hospitalized with confirmed COVID-19 infection for a 6-week period from March 13, 2020, to April 27, 2020. Preadmission antiplatelet regimen continuation for less than 75% of admission was compared to continuation for at least 75% of admission. Pregnancy, either death or withdrawal of care within 24 hours of admission, and admission beyond the studied timeframe were excluded. The primary endpoint was difference in World Health Organization COVID-19 Ordinal Scale for Clinical Improvement values (World Health Organization [WHO] scores) between maximum score during admission to that upon discharge. Secondary endpoints were mechanical ventilation requirement, mortality, radiologically confirmed venous thromboembolism, major bleeding, and length of stay. Results: This study included 171 patients. Patients failing to continue antiplatelet regimens for at least 75% of admission (n = 76) had significantly worse WHO score differences than those who did (n = 95) (median -1 vs 2; P < .05). Mechanical ventilation requirement (57% vs 27%; P < .05) and mortality (58% vs 29%; P < .05) also favored antiplatelet continuation. All other endpoints were not significantly different. Conclusion: Significantly improved WHO scores, mechanical ventilation requirement, and mortality occurred in patients continuing preadmission antiplatelet regimens in COVID-19 infection. Future prospective studies of COVID-19 patients with consistently collected baseline hypercoagulability markers (platelets, D-dimer, fibrinogen, and coagulation studies) and similar severe disease risk factors are required to confirm potential benefits of antiplatelet therapy during hospitalization.

Real-world evaluation of the impact of two anti-SARS-CoV-2 monoclonal antibody regimens on COVID-19 hospitalizations in older adults.

Evidence from clinical trials suggest anti-SARS-CoV-2 monoclonal antibodies (mABs) may reduce coronavirus disease 2019 (COVID-19)-related hospitalizations. The purpose of this study was to assess the real-world impact of mAB administration on COVID-19 hospitalization among patients 65 years or older. This was a retrospective, propensity-matched cohort study that included patients aged 65 years and older who presented to the emergency department (ED) within 10 days of symptom onset of mild to moderate COVID-19 infection. Outcomes were compared between those who did and did not receive mAB therapy. The primary endpoint was the rate of hospitalization for COVID-19 within 30 days of index ED visit. A total of 137 patients receiving mABs were matched to 137 controls. Hospitalization occurred in 2.9% of mAB-treated patients compared to 14.6% of patients of the standard of care (SOC) arm (odds ratio: 0.20 [95% CI: 0.07-0.59]). There were zero intubations and zero deaths compared to 3 (2.2%) and 2 (1.5%) in the SOC group. Among the 223 patients receiving mAB in the overall cohort, adverse drug events occurred in 10 (4.5%). Treatment with mAB therapy for mild to moderate COVID-19 was associated with a substantially reduced risk of hospitalization among patients at least 65 years of age.

Real-World Observational Review of Andexanet Alfa Prescribing and Utilization Outcomes at a Community Teaching Hospital.

OBJECTIVES: Andexanet alfa is the first approved antidote in the management of life-threatening bleeds in patients treated with Xa inhibitors. The ANNEXA-4 study was successful in reducing factor Xa levels during time of administration but lacked correlation to improved patient outcomes. Given its novel mechanism of action, U.S. boxed warning, cost of up to $58,000 per dose, and limited efficacy data compared with standard of care, hospitals are faced with a dilemma with its addition to formulary and process for ensuring optimized use. The objective of this study was to evaluate adherence to institution restriction criteria and the clinical outcomes of treatment for patients for whom andexanet alfa is requested. DESIGN: Retrospective cohort study of andexanet alfa requests within a 12-month time period. SETTING: A 600-bed community teaching hospital. PATIENTS: Patients whom pharmacists received request for dispensing andexanet alfa. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Quality outcomes reviewed compliance to restriction criteria. Clinical outcomes evaluated use of adjunctive blood products, ICU length of stay, hospital length of stay, and hospital mortality. Safety outcomes evaluated incidence of thrombotic events.Andexanet alfa was requested for 16 patients from November 2018 to November 2019. It was administered in nine patients, with compliance to restriction criteria of 66.6%, average ICU length of stay 5.6 days, hospital length of stay 8.6 days, hospital mortality in 44.4%, and thrombotic events in 33.3%. Orders were rejected in seven patients with compliance to restriction criteria of 100%, ICU length of stay 3.2 days, hospital length of stay 5.5 days, hospital mortality in 14%, and thrombotic events in 14%. CONCLUSIONS: A greater rate of adverse effects and mortality was identified with the use of andexanet alfa compared with clinical trials. This is potentially due to its use in a more severely ill patient population and lack of adherence to restriction criteria.

Impact of Expansion of PGY1 Pharmacy Residency Program From 2 to 4 Residents.

PURPOSE: To evaluate the benefits of postgraduate year 1 (PGY1) pharmacy residency program expansion on clinical outcomes, pharmacy services, educational outreach, costs, and preceptor time at a community teaching hospital. METHODS: During academic years 2014 to 2016, two PGY1 resident positions existed, expanding to four PGY1 resident positions during 2016 to 2018. Quantitative analyses comparing the aforementioned periods evaluated clinical interventions, adverse drug events prevented, community and hospital educational programs provided, departmental costs, and documented preceptor hours as a result of program growth. The outcomes were assessed using descriptive statistics. RESULTS: The mean number of documented clinical interventions completed by the resident classes with two residents was 2906 when compared to 5324 with four residents. The mean number of prevented adverse drug events was 56 during the years with two residents and 220 in the years with four residents. The number of community outreach programs increased from 2 to 18 per year. The number of resident lectures provided to allied health professionals increased from 11 to 16 sessions per year. The net economic impact associated with two residents in 2014 was +$4661 USD, while in 2017 the net impact was -$5262 USD. The mean preceptor hours spent per year related to residency activities with two residents was 1005 hours compared to 1109.5 hours with four residents. CONCLUSION: Through strategic modification, expansion of the PGY1 residency program led to increased documentation of clinical interventions, prevented adverse drug events, and educational programs provided with minimal change in preceptor burden.

Prospective Observational Evaluation of Sedation and Pain Management Guideline Adherence Across New Jersey Intensive Care Units.

BACKGROUND: The practice guidelines for the management of pain, agitation, and delirium (PAD) from the Society of Critical Care Medicine shifted from primarily focusing on the treatment of anxiety in 2002 to the treatment of pain in 2013. OBJECTIVE: This prospective, observational, multicenter study aimed to assess the degree of practice adherence to the PAD guidelines for ventilated patients in New Jersey intensive care units (ICUs). METHODS: Pharmacist investigators at 8 centers designated 4 days at least 10 days apart to evaluate all patients on mechanical ventilation. The primary outcomes included adherence to 4 guideline recommendations: treatment of pain before sedation, use of nonnarcotic analgesic medications, use of nonbenzodiazepine sedative medications, and use of goal-directed sedation. RESULTS: Of 138 patients evaluated, 50% had a primary medical diagnosis (as opposed to surgical, cardiac, or neurological diagnosis), and the median Sequential Organ Failure Assessment (SOFA) score was 7. Pain was treated prior to administration of sedatives in 55.4% of subjects, with fentanyl being the primary analgesic used. In addition, 19% received no analgesia, and 11.5% received nonopioid analgesia. Sedative agents were administered to 87 subjects (48 nonbenzodiazepine and 39 benzodiazepine). Of those receiving benzodiazepines, 22 received intermittent bolus regimens and 16 received continuous infusions, of which 5 were for another indication besides sedation. Validated scales measuring the degree of sedation were completed at least once in 56 (81.6%) patients receiving sedatives. CONCLUSIONS: Current sedation practices suggest that integration of evidence-based PAD guidelines across New Jersey adult ICUs is inconsistent despite pharmacist involvement.

Abrupt versus gradual cessation of steroids in patients with septic shock.

PURPOSE: To determine if a difference in hemodynamic stability would be identified in patients with abrupt withdrawal of steroids compared to patients who underwent a taper. MATERIAL AND METHODS: This retrospective cohort study identified patients who received vasopressors followed by IV hydrocortisone for treatment of septic shock from January 1, 2013 until January 1, 2015.The primary endpoint evaluated the percent of patients requiring vasopressor re-initiation during taper and 72 h following taper, or 72 h directly following abrupt withdrawal. Secondary endpoints evaluated include glycemic control, and ICU length of stay. RESULTS: A total of 87 patients were included for final analysis. Of the 87 patients, 7 out of 41 patients (17.1%) in the steroid taper group developed hemodynamic instability and required re-initiation of vasopressors compared to 1 out of 46 patients (2.2%) in the abrupt withdrawal group (p = 0.024). Patients in the taper group also had worse glycemic control (125.1 mg/dL abrupt vs. 150.8 taper; p < 0.001). There was no statistical difference found in the ICU length of stay (8.28 days abrupt vs.10.73 taper; p = 0.14). CONCLUSION: The abrupt withdrawal of steroids in patients with resolving septic shock did not impact hemodynamic stability and offers an opportunity to reduce medication burden and reduce adverse drug reactions.