Performance of Bayesian Area Under the Concentration-Time Curve-Based Pharmacokinetic Dosing Based on a One-Compartment Model and Trough-Only Monitoring for Vancomycin.

A novel Bayesian method was developed to interpret serum vancomycin concentrations (SVCs) following the administration of one or more vancomycin doses with potential varying doses and intervals based on superposition principles. The method was evaluated using retrospective data from 442 subjects from three hospitals. The patients were required to receive vancomycin for more than 3 days, have stable renal function (fluctuation in serum creatinine of ≤0.3 mg/dL), and have at least 2 trough concentrations reported. Pharmacokinetic parameters were predicted using the first SVC, and the fitted parameters were then used to predict subsequent SVCs. Using only covariate-adjusted population prior estimates, the first two SVC prediction errors were 47.3 to 54.7% for the scaled mean absolute error (sMAE) and 62.1 to 67.8% for the scaled root mean squared error (sRMSE). "Scaled" refers to the division of the MAE or RMSE by the mean value. The Bayesian method had minimal errors for the first SVC (by design), and for the second SVC, the sMAE was 8.95%, and the sRMSE was 36.5%. The predictive performance of the Bayesian method did degrade with subsequent SVCs, which we attributed to time-dependent pharmacokinetics. The 24-h area under the concentration-time curve (AUC) was determined from simulated concentrations before and after the first SVC was reported. Prior to the first SVC, 170 (38.4%) patients had a 24-h AUC of <400 mg · h/L, 186 (42.1%) had a 24-h AUC within the target range, and 86 (19.5%) had a 24-h AUC of >600 mg · h/L. After the first SVC was reported, 322 (72.9%) had a 24-h AUC within the target range, 68 (15.4%) had low values, and 52 (11.8%) had high values based on the model simulation. Target attainments were 38% before the first SVC and 73% after the first SVC. The hospitals had no policies or procedures in place for targeting 24-h AUCs, although the trough target was typically 13 to 17 mg/L. Our data provide evidence of time-dependent pharmacokinetics, which will require regular therapeutic drug monitoring regardless of the method used to interpret SVCs.

Comparison of Methicillin-Resistant Staphylococcus aureus Nasal Screening Predictive Value in the Intensive Care Unit and General Ward.

BACKGROUND: The clinical utility of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening appears promising for antimicrobial stewardship programs. However, a paucity of data remains on the diagnostic performance of culture-based MRSA screen in the intensive care unit (ICU) for pneumonia and bacteremia. OBJECTIVE: The objective of this study was to compare the predictive value of culture-based MRSA nasal screening for pneumonia and bacteremia in ICU and general ward patients. METHODS: This multicenter, retrospective study was conducted over a 23-month period. Adult patients with MRSA nasal screening ≤48 hours of collecting a respiratory and/or blood culture with concurrent initiation of anti-MRSA therapy were included. The primary endpoint was to compare the negative predictive value (NPV) associated with culture-based MRSA nasal screening between ICU and general ward patients with suspected pneumonia. RESULTS: A total of 5106 patients representing the ICU (n = 2515) and general ward (n = 2591) were evaluated. The NPV of the MRSA nares for suspected pneumonia was not significantly different between ICU and general ward patient populations (98.3% and 97.6%, respectively; P = 0.41). The MRSA nares screening tool also had a high NPV for suspected bacteremia in ICU (99.8%) and general ward groups (99.7%) (P = 0.56). The overall positive MRSA nares rates in the ICU and general ward patient populations were 9.1% and 8.2%, respectively (P = 0.283). Moreover, MRSA-positive respiratory and blood cultures among ICU patients were 5.8% and 0.8%, respectively. CONCLUSION AND RELEVANCE: Our findings support the routine use of MRSA nasal screening using the culture-based method in ICU patients with pneumonia. Further research on the clinical performance for MRSA bacteremia in the ICU is warranted.

Pharmacokinetic Analysis and In Vitro Synergy Evaluation of Cefiderocol, Sulbactam, and Tigecycline in an Extensively Drug-Resistant Acinetobacter baumannii Pneumonia Patient Receiving Continuous Venovenous Hemodiafiltration.

Antimicrobial treatments for extensively drug-resistant Acinetobacter baumannii (XDR-AB) infections have proven lackluster, while dosing challenges in patients receiving continuous renal replacement therapy continue. We describe a patient receiving cefiderocol, ampicillin/sulbactam, and tigecycline for XDR-AB while undergoing continuous venovenous hemodiafiltration. The clinical course, cefiderocol and sulbactam pharmacokinetics, and synergy assessments are described.

Vancomycin With Concomitant Piperacillin/Tazobactam vs. Cefepime or Meropenem Associated Acute Kidney Injury in General Ward Patients: A Multicenter Propensity Score-Matched Study.

Background: Concurrent administration of vancomycin and piperacillin/tazobactam (VAN+PTZ) may increase the risk of acute kidney injury (AKI) in hospitalized patients. Comprehensive characterization of VAN+PTZ associated AKI and recovery patterns remains lacking in previous reports. Objective: To compare the incidence of AKI associated with VAN+PTZ compared to either cefepime (CEF) or meropenem (MER) with VAN in adult general ward patients. Methods: A multicenter, retrospective, propensity score cohort study was conducted in non-critically ill adult patients. Included patients were concurrently administered VAN+PTZ or VAN+CEF/MER. Patients developing AKI ≤48 hours following combination therapy were excluded. The primary endpoint was to compare the incidence of AKI between study groups. Multivariable Cox regression modeling in predicting AKI was also conducted. Results: A total of 3199 patients met inclusion criteria and were evaluated. The incidence of AKI in VAN+PTZ and VAN+CEF/MER groups were 16.4% and 8.7%, respectively (P < .001). The onset to AKI was 1.8 days earlier with VAN+PTZ compared to VAN+CEF/MER (P < .001). Multivariable prediction model showed concomitant VAN+PTZ was identified as an independent risk factor of developing AKI (HR 2.34, 1.82-3.01, P < .001). The VAN+PTZ group experienced significantly higher rates of severe AKI (stage II or III) compared to the VAN+CEF/MER group (P = .002). No differences in the AKI recovery patterns were found between study groups. Conclusions: Concomitant VAN+PTZ in adult general ward patients was independently associated with an increased risk of AKI overall. More severe AKI was also associated with VAN+PTZ.

Vancomycin with concomitant piperacillin/tazobactam vs. cefepime or meropenem associated acute kidney injury in the critically ill: A multicenter propensity score-matched study.

PURPOSE: The risk of acute kidney injury (AKI) associated with concomitant vancomycin and piperacillin/tazobactam in the intensive care unit (ICU) remains controversial. The aim of this study was to compare the AKI incidence associated with concomitant vancomycin and piperacillin/tazobactam compared to either cefepime or meropenem with vancomycin in the ICU. MATERIALS AND METHODS: A multicenter, retrospective, propensity score-matched cohort study was conducted in adult ICU patients administered vancomycin in combination with either piperacillin/tazobactam, cefepime, or meropenem were included. Patients developing AKI ≤48 h following combination therapy initiation were excluded. The primary endpoint was to compare the incidence of AKI associated with concomitant antimicrobial therapy. Multivariable Cox regression modeling in predicting AKI was also conducted. RESULTS: A total of 1044 patients were matched. The AKI incidence in vancomycin- piperacillin/tazobactam and vancomycin-cefepime/meropenem groups were 21.9% and 16.8%, respectively (p = 0.068). Multivariable prediction models showed concomitant vancomycin-piperacillin/tazobactam was an independent risk factor of AKI using serum creatinine only (HR 1.52, 1.10-2.10, p = 0.011) and serum creatinine with urine output-based KDIGO criteria (HR 1.77, 1.18-2.67, p = 0.006). No significant differences between groups were observed for AKI recovery patterns or mortality. CONCLUSION: Concomitant vancomycin and piperacillin/tazobactam administration in adult ICU patients was independently associated with an increased risk of AKI.

Cefiderocol Pharmacokinetics in a Patient Receiving Continuous Venovenous Hemodiafiltration.

Antimicrobial dosing in patients receiving continuous renal replacement therapy is a continued clinical challenge. We describe a case of a patient receiving cefiderocol 2 g intravenously every 8 hours as a 3-hour infusion for a multidrug-resistant Pseudomonas aeruginosa pneumonia and bacteremia while undergoing continuous venovenous hemodiafiltration. The clinical course and cefiderocol pharmacokinetics are described.

Comparison of acute kidney injury risk associated with vancomycin and concomitant piperacillin/tazobactam or cefepime in the intensive care unit.

PURPOSE: The objective of this study was to evaluate AKI incidence with concomitant vancomycin and piperacillin/tazobactam (PTZ) compared to vancomycin and cefepime (FEP) in critically ill patients. MATERIALS AND METHODS: A retrospective, cohort study was conducted in adult critically ill patients from January 1, 2014 to December 31, 2017. The primary aim was to compare the incidence of AKI during concomitant therapy or until hospital discharge. Secondary analyses included AKI severity, time to AKI as well as recovery, and clinical outcomes. RESULTS: Overall, 333 patients were evaluated. The AKI rate in the vancomycin/PTZ group and vancomycin/FEP group were similar (19.5% vs. 17.3%, respectively, p = .612). Renal replacement therapy (RRT) was initiated in 10.0% and 3.8% administered vancomycin/PTZ and vancomycin/FEP groups, respectively (p = .04). Multivariate regression found vancomycin/PTZ was not associated with an increased risk of developing AKI although the presence of shock was identified as an independent risk factor (odds ratio, 3.22; 95% CI, 1.66-6.26). No significant differences in hospital or ICU length of stay or in-hospital mortality were observed between study groups. CONCLUSIONS: Concomitant PTZ and vancomycin in ICU patients was not associated with an increased risk of developing AKI compared to FEP and vancomycin combinations. More patients administered vancomycin/PTZ received RRT.