Curbing the Delta Surge: Clinical Outcomes After Treatment With Bamlanivimab-Etesevimab, Casirivimab-Imdevimab, or Sotrovimab for Mild to Moderate Coronavirus Disease 2019.

OBJECTIVE: To describe and compare the clinical outcomes of bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab treatment of mild to moderate coronavirus disease 2019 (COVID-19) during the severe acute respiratory coronavirus 2 (SARS-CoV-2) B.1.617.2 Delta surge. METHODS: This is a retrospective study of high-risk patients who received bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab for mild to moderate COVID-19 between August 1, 2021, and December 1, 2021. Rates of severe disease, hospitalization, intensive care unit admission, and death were assessed. RESULTS: Among 10,775 high-risk patients who received bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab for mild to moderate COVID-19 during the Delta surge, 287 patients (2.7%) developed severe disease that led to hospitalization, oxygen supplementation, or death within 30 days after treatment. The rates of severe disease were low among patients treated with bamlanivimab-etesevimab (1.2%), casirivimab-imdevimab (2.9%), and sotrovimab (1.6%; P<.01). The higher rate of severe outcomes among patients treated with casirivimab-imdevimab may be related to a significantly lower COVID-19 vaccination rate in that cohort. Intensive care unit admission was comparable among patients treated bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab (1.0%, 1.0%, and 0.4%, respectively). CONCLUSION: This real-world study of a large cohort of high-risk patients shows low rates of severe disease, hospitalization, intensive care unit admission, and mortality after treatment with bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab for mild to moderate COVID-19 during the SARS-CoV-2 Delta surge.

Comparable Outcomes for Bebtelovimab and Ritonavir-Boosted Nirmatrelvir Treatment in High-Risk Patients With Coronavirus Disease-2019 During Severe Acute Respiratory Syndrome Coronavirus 2 BA.2 Omicron Epoch.

The effectiveness of bebtelovimab in real-world settings has not been assessed. In this retrospective cohort study of 3607 high-risk patients, bebtelovimab was used more commonly than nirmatrelvir-ritonavir for treatment of coronavirus disease 2019 (COVID-19) among older patients, immunosuppressed patients, and those with multiple comorbid conditions. Despite its use in patients with multiple comorbid conditions, the rate of progression to severe disease after bebtelovimab (1.4% [95% confidence interval, 1.2%-1.7%]) was not significantly different from that for nirmatrelvir-ritonavir treatment (1.2% [.8%-1.5%]). Our findings support the emergency use authorization of bebtelovimab for treatment of COVID-19 during the Omicron epoch dominated by BA.2 and subvariants.

Rates of Severe Outcomes After Bamlanivimab-Etesevimab and Casirivimab-Imdevimab Treatment of High-Risk Patients With Mild to Moderate Coronavirus Disease 2019.

Bamlanivimab-etesevimab and casirivimab-imdevimab are authorized by the US Food and Drug Administration for emergency treatment of mild to moderate coronavirus disease 2019 (COVID-19) in high-risk persons. There has been no study comparing their clinical efficacy. In this retrospective study of 681 patients with mild to moderate COVID-19 during a period dominated by severe acute respiratory syndrome coronavirus 2 wild-type and alpha variants, 25 patients (3.7%) had progression to a severe outcome requiring hospitalization and oxygen supplementation within 30 days after monoclonal antibody infusion. Severe outcome was significantly higher among the 181 patients who were treated with casirivimab-imdevimab when compared with the 500 patients who received bamlanivimab-etesevimab (21 [6.6%] vs 13 [2.6%]; P=.01). Patients treated with casirivimab-imdevimab had higher odds of severe outcomes compared with those who received bamlanivimab-etesevimab (odds ratio, 2.67; 95% CI, 1.17 to 6.06). The demographic and clinical characteristics, and the time to monoclonal antibody infusion, of the 2 treatment cohorts were not significantly different. The reason behind this significant difference in the clinical outcomes is unclear, but our observations emphasize potential efficacy differences among antispike monoclonal antibodies against COVID-19. Further clinical studies using larger cohorts of patients are needed to confirm or refute these observations.

Identification of Risk Factors for Acute Kidney Injury from Intravenous Ketorolac in Geriatric Trauma Patients.

BACKGROUND: Ketorolac is an effective analgesic but the potential for acute kidney injury (AKI) is concerning, particularly in geriatric "G-60 trauma" patients. The objectives of this study are to report the incidence of AKI in patients who receive ketorolac, identify risk factors for AKI, and develop a risk factor-guided algorithm for safe utilization. METHODS: This retrospective cohort study included trauma patients age 60 years and older who received intravenous ketorolac. The primary endpoint was the incidence of AKI. RESULTS: Among 316 patients evaluated, the incidence of AKI was 2.5%. Patients with AKI received more nephrotoxins, had more comorbidities, and higher use of loop diuretics or vasopressors. Loop diuretic therapy and number of comorbidities were independent predictors of AKI. CONCLUSIONS: Risk for AKI with ketorolac was low, being more prevalent with comorbidities or receipt of loop diuretics.

Optimizing outcomes using vancomycin therapeutic drug monitoring in patients with MRSA bacteremia: trough concentrations or area under the curve?

BACKGROUND: Vancomycin therapeutic drug monitoring is routinely performed but the specific measure used in practice is variable. OBJECTIVE: To evaluate the relationship between the first measured vancomycin trough, area-under-the-curve (AUC), and failure in patients with MRSA bacteremia. METHODS: This retrospective, cohort study included adult non-neutropenic patients with MRSA bacteremia who received vancomycin. The primary outcome was treatment failure. Initial trough and AUC values were compared between the failure and success groups. Classification and regression tree analysis was used to identify thresholds associated with failure. Multivariate analysis was performed to control for identified confounders. RESULTS: There were 89 patients. Failure occurred in 23 (26%). Trough and AUC values associated with failure were < 10.6 mg/L (39% vs. 13%; P = 0.006) and AUC < 410mg*h/L (40% vs. 17%; P = 0.014). Both remained significant after controlling covariates (trough < 10.6 mg/L, OR [95% CI] = 4.91 [1.6-15]; AUC<410mg*h/L, OR [95% CI] = 3.13 [1.14-8.62]). Only AUC was predictive of nephrotoxicity. CONCLUSION: Failure was more common with troughs < 10.6 mg/L or AUC < 410 mg*h/L. Supratherapeutic AUCs, but not trough, were associated with nephrotoxicity.

The Role of Desmopressin on Hematoma Expansion in Patients with Mild Traumatic Brain Injury Prescribed Pre-injury Antiplatelet Medications.

BACKGROUND/OBJECTIVE: Desmopressin (DDAVP) has been suggested for antiplatelet medication reversal in patients with traumatic brain injury (TBI) but there are limited data describing its effect on clinical outcomes. The purpose of this study was to evaluate the effect of DDAVP on hematoma expansion and thrombosis in patients with TBI who were prescribed pre-injury antiplatelet medications. METHODS: Consecutive adult patients who were admitted to our level I trauma center and prescribed pre-injury antiplatelet medications between July, 2012, and May, 2018, were retrospectively identified. Patients were excluded if their hospital length of stay was < 24 h, if DDAVP was administered by any route other than intravenous, if they received a DDAVP dose < 0.3 mcg/kg or there was no evidence of brain hemorrhage on computed tomography (CT) scan. Patients were stratified based on the use of DDAVP, and the incidence of hematoma expansion was compared between groups. Thrombotic events were reviewed as a secondary outcome. Multivariate analysis was utilized to control for confounding variables. RESULTS: Of 202 patients included in analysis, 158 (78%) received DDAVP. The mean age was 76 ± 12 years; the most common injury mechanism was falls (76%); 69% had acute subdural hematoma, and 49% had multi-compartmental hemorrhage. Initial Glasgow coma score was between 13 and 15 for 91% of patients. Aspirin was the most common antiplatelet regimen prescribed (N = 151, 75%), followed by dual antiplatelet regimens (N = 26, 13%) and adenosine diphosphate (ADP)-receptor inhibitors (N = 25, 12%). The incidence of hematoma expansion was 14% and 30% for patients who did and did not receive DDAVP, respectively (p = 0.015). After controlling for age, injury severity score, multi-compartmental hemorrhage, and receipt of pre-injury high-dose aspirin (> 81 mg), ADP-receptor inhibitors, oral anticoagulants, prothrombin complex concentrates or platelets in a multivariate analysis, the association between DDAVP and hematoma expansion remained significant (adjusted OR 0.259 [95% CI 0.103-0.646], p = 0.004). Thrombotic events were similar between the two groups (DDAVP, 2.5%, no DDAVP, 4.5%; p = 0.613). CONCLUSIONS: DDAVP was associated with a lower incidence of hematoma expansion in patients with mild TBI who were prescribed pre-injury antiplatelet medications. These results justify a randomized controlled trial to further evaluate the role of DDAVP for this indication.

Utilization of Augmented Renal Clearance in Trauma Intensive Care Scoring System to Improve Vancomycin Dosing in Trauma Patients at Risk for Augmented Renal Clearance.

Background: The Augmented Renal Clearance in Trauma Intensive Care (ARCTIC) scoring system is a validated system to predict augmented renal clearance in trauma patients. This study examined the ability of the ARCTIC score to identify patients at risk for subtherapeutic vancomycin trough concentrations relative to estimated creatinine clearance (eCrCl) alone. Methods: Trauma patients admitted to the intensive care unit from September 2012 to December 2017 who received vancomycin and had a vancomycin trough concentration recorded were included. Patients were excluded if their serum creatinine concentration was >1.3 mg/dL, if they had received vancomycin doses <30 mg/kg per day, an improperly timed trough concentration measurement, or renal replacement therapy. The primary endpoint was an initial subtherapeutic vancomycin trough concentration (<10 mg/L). Classification and regression tree (CART) analysis was used to identify thresholds for the ARCTIC score and other continuous data where subtherapeutic troughs were more common. A step-wise logistic regression analysis was performed to control for confounders for subtherapeutic troughs whereby inclusion of ARCTIC was modeled sequentially after eCrCl. Results: A total of 119 patients with a mean age of 42 ± 17 years and eCrCl 142 ± 39 mL/min met the inclusion criteria. The mean daily vancomycin dose was 44 ± 9 mg/kg, and the incidence of subtherapeutic trough concentration was 46%. The CART analysis identified two variables creating three groups where subtherapeutic trough concentrations differed: eCrCl >105 mL/min and ARCTIC score ≥7, eCrCl >105 mL/min and ARCTIC score <7, and eCrCl ≤105 mL/min. The base logistic regression model identified eCrCl >105 mL/min and pelvic fracture as risk factors for subtherapeutic trough values. The final model included the addition of ARCTIC score ≥7, which improved the model significantly (p = 0.009). Predictors of subtherapeutic trough concentrations were (odds ratio [95% confidence interval]): eCrCl >105 mL/min (6.5 [1.66-25.07]), ARCTIC score ≥7 (3.26 [1.31-8.09]), and pelvic fracture (4.36 [1.27-14.93]). Conclusion: The ARCTIC score is useful when applied in conjunction with eCrCl. Patients with a eCrCl >105 mL/min and an ARCTIC score ≥7 may require a more aggressive dosing strategy.

The Risk of Acute Kidney Injury in Critically Ill Patients Receiving Concomitant Vancomycin With Piperacillin-Tazobactam or Cefepime.

PURPOSE: The objective of this study was to compare the incidence of acute kidney injury (AKI) among critically ill patients receiving combination therapy with vancomycin plus piperacillin-tazobactam (VPT) against patients receiving vancomycin plus cefepime (VC). METHODS: A retrospective cohort study of adult patients admitted to an intensive care unit between September 2012 and December 2016 was conducted. Patients were included if they received combination therapy with VPT or VC for ≥48 hours. Patients were excluded if creatinine clearance was <60 mL/min or received renal replacement therapy prior to the initiation of therapy. The primary end point was AKI, as defined by the Acute Kidney Injury Network classification, during or within 48 hours of completion of therapy. The incidence of AKI was compared between groups and multivariate analysis was performed to control for relevant confounders. RESULTS: A total of 394 patients received either VPT (n = 258) or VC (n = 136). There were no differences in baseline serum creatinine (0.8 [0.3]mg/dL vs 0.7 [0.3] mg/dL, P = 0.207), use of vasopressors (44% vs 38%, P = 0.255), mechanical ventilation (45% vs 40%, P = 0.350), or initial vancomycin trough (11.2 [5] mg/L vs 11 [4.8] mg/L, P = 0.668) between VPT and VC groups, respectively. The incidence of AKI was 28.7% for VPT patients versus 21.3% for VC patients (P = 0.114). Multivariate analysis revealed vancomycin trough >20 mg/L (odds ratio, OR [95% confidence interval, CI] = 2.69 [1.62-4.47]), baseline SCr (OR [95% CI] = 3.34 [1.43-7.80]), vasopressors (OR [95% CI] = 1.77 [1.04-3.04]), and duration of combination therapy (OR [95% CI] = 1.009 [1.003-1.015]) as independent risk factors for AKI. CONCLUSION: The risk of AKI was similar between VPT and VC groups in critically ill patients. Risk factors for AKI were related to baseline renal function, duration of combination therapy, supratherapeutic vancomycin troughs, and severity of illness.

Lacosamide versus phenytoin for the prevention of early post traumatic seizures.

PURPOSE: To compare the efficacy and safety of lacosamide versus phenytoin for seizure prophylaxis following TBI. MATERIALS AND METHODS: All TBI patients who received prophylaxis with either phenytoin or lacosamide were retrospectively identified. The incidence of seizures within the first 7 days of injury were compared along with adverse effects requiring drug discontinuation. A planned sub-group analysis was performed for patients with severe TBI (GCS < 9). RESULTS: There were 481 patients (phenytoin, n = 116; lacosamide, n = 365). Demographics were similar but age (50 ±â€¯21 vs 58 ±â€¯22 years, P < .001) and initial GCS (11.3 ±â€¯4.3 vs 12.5 ±â€¯3.8, P = .010) were lower in the phenytoin group. The need for mechanical ventilation was higher (53% vs 38%, P = .004). Seizures occurred in 0.9% of the phenytoin group and 1.4% of the lacosamide group (P = 1.00). ADEs were significantly higher with phenytoin (5.2% vs 0.5%, P = .003). This difference remained significant upon multivariate analysis [OR(95% CI) = 9.4(1.8-48.9)]. Subgroup analysis for patients with severe TBI revealed no difference in seizures (phenytoin, 0% vs lacosamide, 1.5%; P = 1.00) but more ADEs with phenytoin (12.5% vs 0%, P = .010). CONCLUSION: There was no difference between lacosamide and phenytoin in the prevention of early post traumatic seizures in patients following TBI. Lacosamide may have a more tolerable side effect profile.

Fixed-dose 4-factor prothrombin complex concentrate: we don't know where we're going if we don't know how to get there.

4-Factor Prothrombin Complex Concentrate (4F-PCC) is the standard-of-care intervention in patients with major bleeding taking oral vitamin K antagonists. Despite growing clinical experience with 4-FPCC, the optimal dosing strategy remains unclear. In balancing efficacy, safety, and cost of this treatment, many institutions have adopted a low, fixed-dose regimen, with average doses lower than that in the package insert. The fixed-dose 4F-PCC strategy is supported by the available observational studies and case reports; however, the current body of literature is highly heterogenous. The purpose of this narrative review is to address the advantages and shortcomings with clinical use of fixed-dose 4F-PCC, as well as limitations of the available literature. The heterogeneity of the current literature should guide future studies to support or refute this potentially life-saving intervention.

Alternative dosing of prophylactic enoxaparin in the trauma patient: is more the answer?

BACKGROUND: Inadequate anti-factor Xa levels and increased venous thromboembolic events occur in trauma patients receiving standard prophylactic enoxaparin dosing. The aim of this study was to test the hypothesis that higher dosing (40 mg twice daily) would improve peak anti-Xa levels and decrease venous thromboembolism. METHODS: A retrospective review was performed of trauma patients who received prophylactic enoxaparin and peak anti-Xa levels over 27 months. Patients were divided on the basis of dose: group A received 30 mg twice daily, and group B received 40 mg twice daily. Demographics and rates of venous thromboembolism were compared between dose groups and patients with inadequate or adequate anti-Xa levels. RESULTS: One hundred twenty-four patients were included, 90 in group A and 34 in group B. Demographics were similar, except that patients in group B had a higher mean body weight. Despite this, only 9% of group B patients had inadequate anti-Xa levels, compared with 33% of those in group A (P = .01). Imaging studies were available in 69 patients and revealed 8 venous thromboembolic events (P = NS, group A vs group B) with significantly more venous thromboembolic events occurring in patients with low anti-Xa levels (P = .02). CONCLUSIONS: Although higher dosing of enoxaparin led to improved anti-Xa levels, this did not equate to a statistical decrease in venous thromboembolism.