Ceftazidime-Avibactam Activity against Aerobic Gram Negative Organisms Isolated from Intra-Abdominal Infections in United States Hospitals, 2012-2014.
BACKGROUND
Ceftazidime-avibactam is ceftazidime combined with the novel non-β-lactam β-lactamase inhibitor avibactam, which inhibits Ambler class A (e.g., extended-spectrum β-lactamase [ESBL] and KPC), class C, and some class D enzymes. We evaluated the activity of ceftazidime-avibactam against aerobic gram negative bacteria causing intra-abdominal infections (IAI).


METHODS
A total of 1,540 isolates were collected, one each from patient, with IAI in 57 United States hospitals in 2012-2014. Susceptibility testing was performed by reference broth microdilution methods, and Enterobacteriaceae isolates with an ESBL phenotype were evaluated by a microarray-based assay for the presence of genes encoding the CTX-M, TEM, SHV, KPC, NDM, and transferable AmpC enzymes.


RESULTS
All Escherichia coli isolates were susceptible to ceftazidime-avibactam, whereas the susceptibility rates for meropenem, piperacillin-tazobactam, and gentamicin were 99.8%, 93.6%, and 85.5%, respectively. Among Klebsiella pneumoniae isolates, the highest ceftazidime-avibactam minimum inhibitory concentration (MIC) value was only 2 mcg/mL (MIC50/90 0.12/0.25 mcg/mL; 100% susceptible), whereas susceptibility rates to meropenem and gentamicin were 94.5% and 91.9%, respectively. The ESBL-phenotype rates among E. coli and K. pneumoniae were 15.8% and 13.3%, respectively. Overall, only one Enterobacteriaceae isolate (Enterobacter cloacae) was not susceptible to ceftazidime-avibactam and had negative results for all β-lactamases tested. Against Pseudomonas aeruginosa, ceftazidime-avibactam (MIC50/90 2/4 mcg/mL; 97.1% susceptible) and amikacin (MIC50/90 2/8 mcg/mL; 99.0% susceptible) were the most active compounds, and ceftazidime-avibactam retained activity against many meropenem-non-susceptible (88.6% susceptible) and piperacillin-tazobactam-non-susceptible (82.9% susceptible) strains.


CONCLUSIONS
Ceftazidime-avibactam coverage (98.7% inhibited at ≤8 mcg/mL) of intra-abdominal infection pathogens was greater than that observed for meropenem (95.7% susceptible) and piperacillin-tazobactam (88.4% susceptible).
JMI Laboratories , North Liberty, Iowa.
Helio S
HS
Sader
JMI Laboratories , North Liberty, Iowa.
Mariana
M
Castanheira
JMI Laboratories , North Liberty, Iowa.
Robert K
RK
Flamm
JMI Laboratories , North Liberty, Iowa.
Michael D
MD
Huband
JMI Laboratories , North Liberty, Iowa.
Ronald N
RN
Jones
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D053961:Azabicyclo Compounds / Q000627:therapeutic use*; D002442:Ceftazidime / Q000627:therapeutic use*; D004338:Drug Combinations; D006088:Gram-Negative Aerobic Bacteria / Q000187:drug effects / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D059413:Intraabdominal Infections / Q000188:drug therapy* / Q000453:epidemiology; D008826:Microbial Sensitivity Tests; D014481:United States / Q000453:epidemiology
D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D004338:Drug Combinations; C000595613:avibactam, ceftazidime drug combination; D002442:Ceftazidime