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

Antimicrob Agents Chemother 2017 04 24;61(4). Epub 2017 Mar 24.

Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA

Based upon knowledge of the hydrolytic profile of major β-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-β-lactamases (MBLs). Disk diffusion and agar-based antimicrobial susceptibility testing were initially performed to determine the efficacy of a unique combination of CAZ-AVI and ATM against 21 representative isolates with a complex molecular background that included , , , , , and combinations thereof. Time-kill assays were conducted, and the 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 activity of CAZ-AVI in combination with ATM against diverse 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-log-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-log-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 .

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02243-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365724PMC
April 2017
47 Reads

Publication Analysis

Top Keywords

caz-avi
9
infection model
8
time-kill assays
8
mg/kg q8h
8
disk diffusion
8
murine neutropenic
8
caz-avi atm
8
reduction caz-avi
8
caz-avi mg/kg
8
neutropenic thigh
8
thigh infection
8
efficacy combination
8
atm
7
combination
5
addition atm
4
background included
4
included combinations
4
agar dilution
4
combinations time-kill
4
dilution mics
4

References

(Supplied by CrossRef)
Vital signs: carbapenem-resistant Enterobacteriaceae
Centers for Disease Control and Prevention et al.
MMWR Morb Mortal Wkly Rep 2013
Performance standards for antimicrobial susceptibility testing
CLSI et al.
2015

Similar Publications