Chemical and Physical Stability of an Admixture Containing Cefepime and Vancomycin in Lactated Ringer Solution.

Purpose: To evaluate the chemical and physical stability of an admixture containing cefepime and vancomycin in a single volume of lactated Ringer solution at refrigerated temperatures. Methods: Cefepime 2000 mg and vancomycin 1000 mg were, respectively, reconstituted with 10 and 20 mL of sterile water for injection (SWFI) per manufacturer instructions. This resulted in cefepime and vancomycin concentrations of 200 and 50 mg/mL, respectively. The resulting cefepime and vancomycin solutions at 10 and 20 mL, respectively, were drawn up and injected into 1000 mL lactated Ringer solution. Aliquot samples were obtained on days 0 to 9, visually inspected for gross incompatibility, and then stored at -80°C. Samples were thawed on the day of the analysis and run through ultraperformance liquid chromatography. Area under the concentration-time curve (AUC) on each day was compared with baseline AUC values. Chemical stability was defined as an AUC more than 93% of the baseline value. Results: No evidence of gross physical incompatibility was observed by visual inspection. Cefepime and vancomycin replicants were more than 94.5% and 98% of baseline AUC values. Therefore, all sample replicants were found to be more than 93% of their baseline AUC value. Conclusion: An admixture containing cefepime 2000 mg and vancomycin 1000 mg in 1000 mL lactated Ringer solution appears to be chemically and physically stable at refrigerated temperatures for up to 9 days.

Cefiderocol for treatment of an empyema due to extensively drug-resistant Pseudomonas aeruginosa: Clinical observations and susceptibility testing considerations.

Cefiderocol is a novel siderophore cephalosporin antibacterial with activity against carbapenem-resistant Gram-negative bacteria including Pseudomonas aeruginosa. We report a medically complex patient treated with compassionate use cefiderocol for an empyema caused by extensively drug-resistant P. aeruginosa as well as clinical considerations for cefiderocol use based on our findings. We observed a potential discordance in cefiderocol susceptibility testing results depending if disk diffusion or iron-depleted cation-adjusted Mueller Hinton Broth dilution is used. Furthermore, interpretative criteria differ between the Clinical Laboratory Standards Institute and United States Food and Drug Administration for P. aeruginosa, which makes cefiderocol interpretation potentially challenging for clinicians. We may have also observed selective pressure from prior cefiderocol exposure given the respective increases and decreases in MIC values and zone diameters for P. aeruginosa isolates following cefiderocol treatment. Additional data are needed to further describe cefiderocol use, susceptibility testing, and resistance development as real-world clinical use expands.

Nephrotoxicity Risk and Clinical Effectiveness of Continuous versus Intermittent Infusion Vancomycin Among Patients in an Outpatient Parenteral Antimicrobial Therapy Program.

STUDY OBJECTIVE: To compare rates of nephrotoxicity, time to nephrotoxicity onset, and clinical failure among patients who received continuous infusion (C-I) or intermittent infusion (I-I) vancomycin in an outpatient parenteral antimicrobial therapy (OPAT) program. Nephrotoxicity was defined as an increase in serum creatinine greater than 0.5 mg/dl or a 50% increase from baseline for two consecutive measurements while receiving vancomycin during OPAT. Clinical failure was defined as unplanned readmission, extension of therapy, or change in antibiotics. DESIGN: Single-center propensity score-matched retrospective cohort study. SETTING: OPAT clinic affiliated with two nearby hospitals. PATIENTS: We identified 300 patients who received C-I or I-I vancomycin for at least 1 week in the OPAT program between October 1, 2017, and March 31, 2019. Propensity score matching based on age, sex, and infection was performed to minimize differences in patient characteristics between groups. MEASUREMENTS AND MAIN RESULTS: After propensity score matching and exclusion criteria, 74 patients were included in each cohort. Continuous infusion vancomycin was associated with a 3.22-fold decrease in nephrotoxicity risk (C-I 6.8% [5/74 patients] vs I-I 18.9% [14/74 patients]; odds ratio 3.22, 95% confidence interval 1.10-9.46, p=0.027) and a significantly slower onset to nephrotoxicity compared with I-I (p=0.035). No statistically significant difference in clinical failure rates was observed between the C-I and I-I groups (13.5% [10/74 patients] vs 23.0% [17/74 patients], p=0.147). CONCLUSION: In an OPAT setting, C-I vancomycin was associated with a lower risk of and slower onset to nephrotoxicity than I-I vancomycin; however, no statistically significant difference in clinical failure rates was observed with C-I versus I-I vancomycin.