Utility of fosfomycin as antibacterial prophylaxis in patients with hematologic malignancies.

PURPOSE: Prolonged and profound neutropenia is common among hematology and hematopoietic stem cell transplant (HSCT) patients as a result of chemotherapy. The National Comprehensive Cancer Network (NCCN) and Infectious Diseases Society of America (IDSA) currently recommend antibacterial prophylaxis in patients who are deemed at intermediate or high risk for infection. Specifically, fluoroquinolone prophylaxis should be considered for high-risk neutropenic patients. However, with prolonged and frequent exposure to fluoroquinolones, these high-risk patients may develop resistance to these agents. Patients may also have allergies or other contraindications which prohibit the use of fluoroquinolones for antibacterial prophylaxis. Unfortunately, there is no standard recommendation for alternative antimicrobial therapy in this patient population, as well as there is a lack of data to support the use of potential alternative agents. METHODS: Currently, Yale-New Haven Hospital utilizes fosfomycin for antibacterial prophylaxis in patients who are not eligible for fluoroquinolone therapy. The primary objective of this study was to assess the incidence of breakthrough infections in this population receiving fosfomycin. Secondary objectives included organisms identified, types of breakthrough infections, resistance patterns, and time from initiation to onset of fever. RESULTS: Of the 42 patients who received fosfomycin, 25 patients with 42 admissions met inclusion criteria. A total of 8 (19%) breakthrough infections occurred during the 42 admissions. Organisms included Klebsiella spp. (5), Streptococcus mitis/viridans (2), Pseudomonas aeruginosa (1), and coagulase-negative staphylococcus (1). Infections included the following: bacteremia (7), cellulitis (1), and urine (1). CONCLUSION: Given the low rate of breakthrough infections, fosfomycin may be a potential alternative option for antibacterial prophylaxis.

Comparison of Rates of Nephrotoxicity Associated with Vancomycin in Combination with Piperacillin-Tazobactam Administered as an Extended versus Standard Infusion.

STUDY OBJECTIVE: Despite recent reports of relatively high rates (16-37%) of acute kidney injury (AKI) in patients receiving the combination of intravenous piperacillin-tazobactam (PTZ) and vancomycin, data are limited evaluating the impact of PTZ infusion strategy on the occurrence of nephrotoxicity. The objective of this study was to compare the rates of nephrotoxicity in patients receiving vancomycin in combination with PTZ administered as an extended infusion (EI) versus a standard infusion (SI). DESIGN: Single-center, retrospective, matched-cohort study. SETTING: Large academic tertiary care hospital. PATIENTS: Two hundred eighty adults with a creatinine clearance (CrCl) of 40 ml/minute or higher who received at least 96 hours of vancomycin plus PTZ EI (140 patients) or vancomycin plus PTZ SI (140 patients) between January 1, 2009, and December 31, 2011, and between January 1, 2013, and December 31, 2014 (year 2012 was skipped due the closure of inpatient units following Superstorm Sandy); 48 patients in each group were admitted to the intensive care unit. MEASUREMENTS AND MAIN RESULTS: The median age of all patients was 67 (interquartile range [IQR] 54-77) years, and CrCl was 75 (IQR 55-107) ml/minute. Nephrotoxicity was assessed by the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN) criteria. Rates of AKI, according to these criteria, were similar between groups: 17.9% versus 17.1% (p=1) and 32.9% versus 29.3% (p=0.596) for the PTZ EI and PTZ SI groups, respectively. When controlling for residual differences between groups in a conditional logistic regression analysis, no association was observed between receipt of PTZ EI and RIFLE-defined AKI (odds ratio 0.522, 95% confidence interval 0.043-6.295, p=0.609). Time to onset of nephrotoxicity was 4 (IQR 3-6) days, with no significant difference noted between groups (p=0.887). CONCLUSION: Our findings suggest a similar rate of nephrotoxicity between patients who received vancomycin in combination with PTZ EI versus PTZ SI. These results need to be further validated in a prospective randomized controlled study.