Nephrotoxicity of Vancomycin in Combination With Beta-Lactam Agents: Ceftolozane-Tazobactam vs Piperacillin-Tazobactam.

BACKGROUND: Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactams (BLs) such as piperacillin-tazobactam (TZP) but has not been evaluated with ceftolozane-tazobactam (C/T). Our aim was to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared with VAN in combination to TZP (VAN-TZP). METHODS: We conducted a multicenter, observational, comparative study across the United States. The primary analysis was a composite outcome of AKI and risk, injury, failure, loss, end stage renal disease; Acute Kidney Injury Network; or VAN-induced nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis was conducted to adjust for confounding variables and stratified Kaplan-Meir analysis to assess the time to nephrotoxicity between the 2 groups. RESULTS: We included VAN/C/T (n = 90) and VAN-TZP (n = 284) at an enrollment ratio of 3:1. The primary outcome occurred in 12.2% vs 25.0% in the VAN-C/T and VAN-TZP groups, respectively (P = .011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with VAN-C/T; with an adjusted odds ratio of 3.308 (95% confidence interval, 1.560-6.993). Results of the stratified Kaplan-Meir analysis with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients who received VAN-TZP (P = .004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = .001). CONCLUSIONS: Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to piperacillin, which is a component in VAN-TZP but not in VAN-C/T.

Use of Fluoroquinolones or Sulfamethoxazole-Trimethoprim Compared to Β-Lactams for Oral Step-Down Therapy in Hospitalized Patients With Uncomplicated Enterobacterales Bacteremia.

BACKGROUND: Antibiotic therapy for uncomplicated Enterobacterales bacteremia from a urinary source has traditionally consisted of fluoroquinolones (FQs) and sulfamethoxazole-trimethoprim (SXT). However, adverse events associated with FQs and emerging antimicrobial resistance have led to alternative agents, specifically oral Β-lactams (OBLs), being utilized despite concern of subtherapeutic serum concentrations related to their low relative bioavailability. OBJECTIVE: To compare efficacy of antibiotic therapies with bioavailability differences in patients with uncomplicated bacteremia from a urinary source. METHODS: This was a retrospective study comparing clinical efficacy in hospitalized adult patients receiving OBL or FQ/SXT. Patients were required to receive at least 48 hours of appropriate intravenous antibiotic therapy and at least one dose of oral therapy. The primary outcome was all-cause hospital readmission within 30 days of discharge. Secondary outcomes included readmission with recurrent infectious etiology and readmission due to Clostridioides difficile infection. RESULTS: Of 210 eligible patients, 91 received FQ/SXT and 119 received OBL. There was no difference between the groups in all-cause hospital readmission (FQ/SXT: 16.5%; OBL: 14.3%) (P = 0.660 [95% confidence interval, CI = -0.076, 0.120]) or readmission with recurrent bacteremia (FQ/SXT: 0%; OBL: 3.4%) (P = 0.135). There was a significant difference in repeat hospital admission with recurrent urinary tract infection (UTI) (FQ/SXT: 0%, OBL: 5.0%) (P = 0.037). CONCLUSION AND RELEVANCE: OBLs appear to be non-inferior to FQ/SXT in the rate of all-cause hospital readmission within 30 days. However, OBLs may be associated with increased readmissions with recurrent UTI.

Evaluation of a Rapid Fungal Detection Panel for Identification of Candidemia at an Academic Medical Center.

This study was conducted to assess the utility of the T2Candida panel across an academic health center and identify potential areas for diagnostic optimization. A retrospective chart review was conducted on patients with a T2Candida panel and mycolytic/fungal (myco/f lytic) blood culture collected simultaneously during hospitalizations from February 2017 to March 2018. The primary outcome of this study was to determine the sensitivity, specificity, and positive and negative predictive values of the panel compared to myco/f lytic blood culture. Secondary outcomes included Candida species isolated from culture or detected on the panel, source of infection, days of therapy (DOT) of antifungals in patients with discordant results, and overall antifungal DOT/1,000 patient days. A total of 433 paired T2Candida panel and myco/f lytic blood cultures were identified. The pretest likelihood of candidemia was 4.4%. The sensitivity and specificity were 64.7% and 95.6%, respectively. The positive and negative predictive values were 40.7% and 98.5%, respectively. There were 16 patients with T2Candida panel positive and myco/f lytic blood culture negative results, while 6 patients had T2Candida panel negative and myco/f blood culture positive results. The overall antifungal DOT/1,000 patient days was improved after implementation of the T2Candida panel; however, the use of micafungin continued to decline after the panel was removed. We found that the T2Candida panel is a highly specific diagnostic tool; however, the sensitivity and positive predictive value may be lower than previously reported when employed in clinical practice. Clinicians should use this panel as an adjunct to blood cultures when making a definitive diagnosis of candidemia.

Susceptibility Provision Enhances Effective De-escalation (SPEED): utilizing rapid phenotypic susceptibility testing in Gram-negative bloodstream infections and its potential clinical impact.

Objectives: We evaluated the performance and time to result for pathogen identification (ID) and antimicrobial susceptibility testing (AST) of the Accelerate Pheno™ system (AXDX) compared with standard of care (SOC) methods. We also assessed the hypothetical improvement in antibiotic utilization if AXDX had been implemented. Methods: Clinical samples from patients with monomicrobial Gram-negative bacteraemia were tested and compared between AXDX and the SOC methods of the VERIGENE® and Bruker MALDI Biotyper® systems for ID and the VITEK® 2 system for AST. Additionally, charts were reviewed to calculate theoretical times to antibiotic de-escalation, escalation and active and optimal therapy. Results: ID mean time was 21 h for MALDI-TOF MS, 4.4 h for VERIGENE® and 3.7 h for AXDX. AST mean time was 35 h for VITEK® 2 and 9.0 h for AXDX. For ID, positive percentage agreement was 95.9% and negative percentage agreement was 99.9%. For AST, essential agreement was 94.5% and categorical agreement was 93.5%. If AXDX results had been available to inform patient care, 25% of patients could have been put on active therapy sooner, while 78% of patients who had therapy optimized during hospitalization could have had therapy optimized sooner. Additionally, AXDX could have reduced time to de-escalation (16 versus 31 h) and escalation (19 versus 31 h) compared with SOC. Conclusions: By providing fast and reliable ID and AST results, AXDX has the potential to improve antimicrobial utilization and enhance antimicrobial stewardship.

Evaluation of the Impact of a Student Pharmacist-Supported Program to Improve Hospital-Based Quality Measures.

Background. Although previous studies have demonstrated positive impact of student pharmacists on clinical interventions, no published studies to date have demonstrated the specific impact of student pharmacists on improving National Hospital Inpatient Quality Measures (NHIQM). Objective. To evaluate the impact of a student pharmacist-supported program targeted at improving the venous thromboembolism (VTE) quality measures set forth by the NHIQM. Methods. Retrospective review of VTE quality measure compliance at a community nonteaching hospital. During this time, student pharmacists supported a VTE prophylaxis program that evaluated admitted patients for chemical or mechanical prophylaxis needs. Compliance to VTE quality measures were also evaluated by a trained medical data abstractor based on criteria given by the Joint Commission. Results. Four major NHIQM criteria for VTE were selected for evaluation. National and state averages were compared to the overall hospital averages across various timeframes. The student-supported program demonstrated consistently high performance for the VTE-1 and VTE-5 measures. Conclusion. Student pharmacists have opportunities in improving inpatient quality measures and can play a significant role in patient care through thorough evaluation and intervention.