Vancomycin area under the curve versus trough only guided dosing and the risk of acute kidney injury: Systematic review and meta-analysis.

Vancomycin is commonly used to treat methicillin-resistant Staphylococcus aureus infections and is known to cause nephrotoxicity. Previous Vancomycin Consensus Guidelines recommended targeting trough concentrations but the 2020 Guidelines suggest monitoring vancomycin area under the curve (AUC) given the reduced risk of acute kidney injury (AKI) at similar levels of efficacy. This meta-analysis compares vancomycin-induced AKI incidence using AUC-guided dosing strategies versus trough-based monitoring. Literature was queried from Medline (Ovid), Web of Science, and Google Scholar from database inception through November 5, 2021. Interventional or observational studies reporting the incidence of vancomycin-induced AKI between AUC- and trough-guided dosing strategies were included. In the primary analysis, the Vancomycin Consensus Guidelines definition for AKI was used if reported; otherwise, the Risk, Injury, and Failure; and Loss, and End-stage kidney disease (RIFLE) or Kidney Disease Improving Global Outcomes (KDIGO) definitions were used. The incidence of nephrotoxicity was evaluated between the two strategies using a Mantel-Haenszel random-effects model, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses for adjusted ORs and AKI definitions were performed. Heterogeneity was identified using Cochrane's Q test and I2 statistics. A total of 10 studies with 4231 patients were included. AUC-guided dosing strategies were associated with significantly less vancomycin-induced AKI than trough-guided strategies [OR 0.625, 95% CI (0.469-0.834), p = 0.001; I2  = 25.476]. A subgroup analysis of three studies reporting adjusted ORs yielded similar results [OR 0.475, 95% CI (0.261-0.863), p = 0.015]. Stratification by AKI definition showed a significant reduction in AKI with the Vancomycin Consensus Guidelines definition [OR 0.552, 95% CI (0.341-0.894), p = 0.016] but failed to find significance in the alternative definitions. Area under the curve-guided dosing strategies are associated with a lower incidence of vancomycin-induced AKI versus trough-guided dosing strategies (GRADE, low). Limitations included the variety of AKI definitions and the potential for confounding bias.

Comparative Efficacy of Early COVID-19 Monoclonal Antibody Therapies: A Retrospective Analysis.

Background: Bamlanivimab and casirivimab/imdevimab are monoclonal antibody (mAb) treatments used for mild to moderate coronavirus disease 2019 (COVID-19) in high-risk patients. To date, there are few data summarizing real-world evidence comparing the 2 mAbs. Additionally, there are insufficient data to guide administration timing relative to symptom onset. The purpose of this study was to evaluate 30-day failure rates for each agent and to identify the relationship between symptom onset and efficacy. Methods: We performed a retrospective cohort study of a 6-month period at a large community medical center. Consecutive outpatients diagnosed with COVID-19 disease by nasopharyngeal (NP) polymerase chain reaction (PCR) testing received either bamlanivimab 700 mg or casirivimab/imdevimab 1200 mg/1200 mg. Each patient was followed for a total of 30 days. Three independent, blinded physicians performed adjudication for revisit reasons. The primary outcome was therapy-related failure, defined as COVID-19-related hospital admission within 30 days of infusion. Multivariable logistic regression was performed to adjust for confounders that may have influenced hospital admission in either group. Results: During the period from November 2020 to May 2021, 183 patients were treated with bamlanivimab and 270 with casirivimab/imdevimab. The mean age was ~67 years and body mass index 30 kg/m2. Thirty-day admission for therapy-related failure rates were 4.8% and 13.7% for casirivimab/imdevimab and bamlanivimab, respectively (P = .001). No significant differences were found between early (<3 days of symptom onset) and late administration of either mAb. Conclusions: There was a higher failure rate with bamlanivimab vs casirivimab/imdevimab. No difference in efficacy was found between early vs late administration of either mAb.