Can Ceftazidime-Avibactam and Aztreonam Overcome ß-Lactam Resistance Conferred by Metallo-ß-Lactamases in Enterobacteriaceae?

Based upon knowledge of the hydrolytic profile of major ß-lactamases found in Gram-negative bacteria, we tested the efficacy of the combination of ceftazidime-avibactam (CAZ-AVI) with aztreonam (ATM) against carbapenem-resistant enteric bacteria possessing metallo-ß-lactamases (MBLs). Disk diffusion and agar-based antimicrobial susceptibility testing were initially performed to determine the in vitro efficacy of a unique combination of CAZ-AVI and ATM against 21 representative Enterobacteriaceae isolates with a complex molecular background that included blaIMP, blaNDM, blaOXA-48, blaCTX-M, blaAmpC, and combinations thereof. Time-kill assays were conducted, and the in vivo efficacy of this combination was assessed in a murine neutropenic thigh infection model. By disk diffusion assay, all 21 isolates were resistant to CAZ-AVI alone, and 19/21 were resistant to ATM. The in vitro activity of CAZ-AVI in combination with ATM against diverse Enterobacteriaceae possessing MBLs was demonstrated in 17/21 isolates, where the zone of inhibition was ≥21 mm. All isolates demonstrated a reduction in CAZ-AVI agar dilution MICs with the addition of ATM. At 2 h, time-kill assays demonstrated a ≥4-log10-CFU decrease for all groups that had CAZ-AVI with ATM (8 µg/ml) added, compared to the group treated with CAZ-AVI alone. In the murine neutropenic thigh infection model, an almost 4-log10-CFU reduction was noted at 24 h for CAZ-AVI (32 mg/kg every 8 h [q8h]) plus ATM (32 mg/kg q8h) versus CAZ-AVI (32 mg/kg q8h) alone. The data presented herein require us to carefully consider this new therapeutic combination to treat infections caused by MBL-producing Enterobacteriaceae.

Seizures during pegylated interferon and ribavirin therapy for chronic Hepatitis C: observations from the WIN-R trial.

BACKGROUND: Seizures are reported as an uncommon side effect of interferon therapy. AIM: To determine the frequency and presentation of seizures occurring during pegylated interferon-α (PEG-IFNα) and ribavirin therapy for chronic hepatitis C. METHODS: Patients were identified using data from the WIN-R trial database, a US multicenter study comparing fixed (800 mg) versus weight-based (800 to 1400 mg) daily dosing of ribavirin in combination with PEG-IFNα-2b (1.5 µg/kg/wk). RESULTS: Of the 4913 enrolled patients, 8 (0.16%) had a seizure. Three patients had a grand mal seizure and the seizure type was unknown in 5 patients. At the time of seizure, 6 patients were taking antidepressants (including 3 on bupropion), 1 was hyponatremic, and 1 had consumed a significant amount of alcohol. One patient had a history of seizures. Neuroimaging and electroencephalographic studies were negative. Antiepileptic medications were continued in the patient with a history of seizures and initiated in 1 patient. PEG-IFNα-2b plus ribavirin therapy was continued in 2 patients following seizure and neither experienced a recurrent seizure. CONCLUSIONS: Seizures occur infrequently in patients receiving PEG-IFNα-2b plus ribavirin, and appear to be associated with other risk factors including antidepressant use.

The value of infectious diseases specialists: non-patient care activities.

Recent developments in health care have focused efforts on both the national and local levels to reduce unnecessary health care costs and the number of hospital stays while increasing the quality of care, particularly in the context of hospital-associated infections. Infectious diseases specialists who contract to oversee infection-control and antibiotic-stewardship programs are uniquely positioned to play a pivotal role in helping hospitals to prosper in this new environment. This article will detail the available data supporting the value of infectious diseases specialists in their roles of directing antimicrobial-management and infection-control programs, maintaining health care workers' well-being, and minimizing exposure. The evidence in support of the influence of infectious diseases specialists to achieve cost-savings, decrease the length of hospital stays, and improve outcomes is robust and can be used as the framework for negotiating appropriate compensation from hospital management for these activities. Presenting this information in an amicable but definitive framework may be the linchpin to the overall success of the movement to improve quality of care while minimizing hospital costs and antimicrobial use. Developing this ability is critical to infectious diseases specialists' success as they redefine their role in the quality-of-care and risk-management arenas.