Which "weigh" to Go? Alternative Vancomycin Dosing Strategies in Obese Patients.

PurposeThis study aims to compare the performance of alternative weight-based vancomycin dosing strategies to traditional dosing in obese patients using area under the curve (AUC) monitoring. Methods: This retrospective study compared target attainment of an AUC between 400-600mcg*H/mL using alternative vancomycin dosing strategies. All patients received allometrically dosed vancomycin, with patient-specific AUCs calculated using 2 post-infusion steady-state vancomycin serum concentrations using the trapezoidal rule. Predicted AUCs were calculated using the following: 15 mg/kg total body weight (TBW), 15 mg/kg corrected body weight (CBW), and 12.5 mg/kg TBW. Predicted AUCs from the traditional 15 mg/kg TBW dosing were then compared to alternative dosing strategies using the predicted AUCs from 12.5 mg/kg TBW, 15 mg/kg CBW, and the actual AUCs calculated using allometrically scaled vancomycin dosing. The primary outcome was attainment of initial AUC within the target range of 400-600mcg*H/mL for each dosing method. Results: Eighty-four patients were included. When AUCs were compared to traditional 15 mg/kg dosing strategy, the CBW, 12.5 mg/kg, and allometric dosing strategies were significantly more likely to result in initial attainment of an AUC within a target range of 400-600 mcg*H/mL (P = 0.0003, 0.0135, and 0.0088, respectively). No significant differences were seen between each of the alternative dosing methods (P = 0.73). Conclusion: The 3 alternative vancomycin dosing strategies examined were all significantly more likely to achieve an initial AUC within the target range compared to traditional vancomycin dosing in obese patients. Clinicians should strongly consider one of these alternative dosing strategies for obese patients as opposed to traditional vancomycin dosing.

Evaluating the Safety of Trough Versus Area Under the Curve (AUC)-Based Dosing Method of Vancomycin With Concomitant Piperacillin-Tazobactam.

Background: Vancomycin and piperacillin-tazobactam (VPT) is a common antibiotic combination used in hospitals, and there has been increasing data indicating that the combination is associated with increased rates of acute kidney injury (AKI). It is unclear if the dosing method of vancomycin would mitigate the risk of AKI seen with VPT. Objective: To observe and compare incidence of AKI in patients on VPT when using the trough-based dosing method versus the area-under-the-curve (AUC)-based dosing method. Methods: This was a multi-center, retrospective, observational study at 3 community hospitals. Adults receiving at least 48 hours of VPT were included. Patients with severe renal dysfunction, pregnant patients, prisoners, and patients with central nervous system infections, or malignancy were excluded. The primary outcome was incidence of AKI as defined by the Infectious Disease Society of America (IDSA) criteria. Results: A total of 300 patients were included in the study; 150 patients in both the trough and AUC groups. A total of 23 patients (15%) in the trough group and 17 patients (11%) in the AUC group met the primary outcome (odds ratio [OR]: 0.7058, 95% confidence interval [CI]: [0.3603, 1.3826], P = .3098). Conclusion and Relevance: The incidence of AKI was lower in the AUC group compared with the trough group; however, this was not significant. The results of our study suggest that there is no difference between incidence of AKI when using trough- or AUC-based dosing in those receiving VPT. Because of the small sample size and retrospective nature of the study, more data are needed.

Evaluation of Monoclonal Antibodies in Preventing Hospitalizations, Emergency Department Visits, and Mortality in High-Risk COVID-19 Patients.

Background: The coronavirus disease 2019 (COVID-19) is a novel coronavirus that has caused an unprecedented global pandemic, with few treatment options currently available. Neutralizing monoclonal antibodies (mAbs) are a promising treatment approach to reduce hospitalizations in high-risk patients with mild-to-moderate COVID-19 infections. Objective: The primary objective is to compare hospitalization rates of high-risk patients who tested positive for COVID-19 within 28 days between those who received mAb infusions versus those who did not. Secondary objectives were emergency department (ED) visits and mortality within 28 days of a positive test. Methods: This single-center, institutional review board-approved, retrospective, observational cohort study included patients aged 19 years and older who tested positive for COVID-19 between December 2, 2020 and February 28, 2021. Patients who received the mAbs bamlanivimab or casirivimab/imdevimab were compared with patients who did not receive mAb infusions to examine hospitalization rates, ED visits, and mortality within 28 days of the positive COVID-19 test. Results: A total of 2780 patients were evaluated for inclusion using electronic chart review via Cerner. Of the 1612 patients who met inclusion criteria, 568 received an mAb infusion (mAb group) and 1044 did not (non-mAb group). Baseline characteristics were similar between the 2 groups. Of the patients in the mAb group, 34 (6%) were hospitalized versus 397 (38%) in the non-mAb group. Patients with ED visits included 111 (20%) and 672 (64%) in the mAb and non-mAb groups, respectively. Finally, 5 patients in the mAb group experienced mortality (0.9%) versus 83 (8%) in the non-mAb group. Each endpoint achieved statistical significance with a P value of <0.0001. Conclusion: Monoclonal antibody infusions are effective in preventing hospitalization, ED visits, and mortality in high-risk patients with mild-to-moderate COVID-19.

Novel method of calculating adjusted antibiotic use by microbiological burden.

OBJECTIVE: To determine the usefulness of adjusting antibiotic use (AU) by prevalence of bacterial isolates as an alternative method for risk adjustment beyond hospital characteristics. DESIGN: Retrospective, observational, cross-sectional study. SETTING: Hospitals in the southeastern United States. METHODS: AU in days of therapy per 1,000 patient days and microbiologic data from 2015 and 2016 were collected from 26 hospitals. The prevalences of Pseudomonas aeruginosa, extended-spectrum ß-lactamase (ESBL)-producing bacteria, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) were calculated and compared to the average prevalence of all hospitals in the network. This proportion was used to calculate the adjusted AU (a-AU) for various categories of antimicrobials. For example, a-AU of antipseudomonal ß-lactams (APBL) was the AU of APBL divided by (prevalence of P. aeruginosa at that hospital divided by the average prevalence of P. aeruginosa). Hospitals were categorized by bed size and ranked by AU and a-AU, and the rankings were compared. RESULTS: Most hospitals in 2015 and 2016, respectively, moved ≥2 positions in the ranking using a-AU of APBL (15 of 24, 63%; 22 of 26, 85%), carbapenems (14 of 23, 61%; 22 of 25; 88%), anti-MRSA agents (13 of 23, 57%; 18 of 26, 69%), and anti-VRE agents (18 of 24, 75%; 15 of 26, 58%). Use of a-AU resulted in a shift in quartile of hospital ranking for 50% of APBL agents, 57% of carbapenems, 35% of anti-MRSA agents, and 75% of anti-VRE agents in 2015 and 50% of APBL agents, 28% of carbapenems, 50% of anti-MRSA agents, and 58% of anti-VRE agents in 2016. CONCLUSIONS: The a-AU considerably changes how hospitals compare among each other within a network. Adjusting AU by microbiological burden allows for a more balanced comparison among hospitals with variable baseline rates of resistant bacteria.

Allometric versus consensus guideline dosing in achieving target vancomycin trough concentrations.

PURPOSE: Results of a study comparing the performance of allometric versus consensus guideline-recommended vancomycin dosing in achieving initial trough concentrations within the desired range are reported. METHODS: A retrospective study was conducted to compare selected outcomes with 2 vancomycin dosing methods: (1) dosing by total body weight, as recommended in current consensus guidelines, and (2) a new empirical vancomycin dosing strategy grounded in allometry (the study of the relationship between body size and physiology). The primary outcome was attainment of an initial vancomycin trough concentration within the target range (10-20 mg/L). Rates of nephrotoxicity associated with the 2 dosing methods were compared. RESULTS: Allometric dosing resulted in 77% of the evaluated patient sample (n = 81) achieving vancomycin trough concentration targets at the initial measurement, as compared with a target attainment rate of 57% (n = 81) with guideline-recommended dosing (p = 0.0121); the rate of target attainment in obese patients was also improved with allometric dosing (73% versus 46%, p = 0.0327). Nephrotoxicity rates did not differ significantly between the 2 groups, but a lower rate was observed with allometric versus guideline-based dosing (1.2% versus 7.4%, p = 0.0584). CONCLUSION: In hospitalized adults, allometric vancomycin dosing achieved a higher frequency of initial vancomycin trough concentrations within the target range of 10-20 mg/L, compared with dosing as recommended by consensus guidelines. The difference between methods in the percentage of troughs within the target range was most pronounced in obese patients.