Patients with cancer develop bacterial infections often, especially during periods of neutropenia. Increasing problems with older agents (reduced susceptibility, overt resistance, and toxicity) has highlighted the need to develop newer agents. Ceftazidime-avibactam is a novel agent and is bactericidal against β-lactamase-producing Gram-negative bacilli that might be useful in this setting.
Clinical bacterial isolates were collected from the patient with blood stream infection at University of Texas MD Anderson Cancer Center. The minimum inhibitory concentration (MIC) of 511 gram negative isolates were determined for different antibiotics CAZ-AVI, meropenem (MEM), ceftazidime (CAZ), piperacillin-tazobactam (TZP) and cefepime (FEP) using the broth microdilution method in accordance with CLSI guidelines. All samples were tested in duplicate. Isolates were stratified by species and resistance profile, including extended spectrum B-lactamase (ESBL +, ESBL -) and carbapenemase production. . MIC50 and MIC90analyses were conducted to examine antibiotic resistance.
CAZ-AVI was active against (ESBL- , ESBL+ Phenotype Escherichia coli and K. pneumoniae including ESBL+ strains. MIC50/MIC90 of 0.6/1 ug/ml; Among non MDR P. aeruginosa strains the MIC50/MIC90 were 2/4 ug/ml ; for MDR P. aeruginosa strains the MIC50/MIC90 were 4/>32 ug/ml ,However the MIC90 for MEM, CAZ, TZP and FEP were >32, 64,256 and 64 respectively. Ceftazidime-avibactam was highly active against carbapenem resistant Enterobacteriaciae (CRE) MIC50/MIC90, 1/4 ug/ml. Compared to CAZ, TZP, and FEP.
CAZ-AVI demonstrated potent activity against a large collection of gram-negative organisms identified in our cancer patients. CAZ-AVI was more active than currently available B- lactams, including towards organisms that are resistant to most currently available agents, such as CRE and MDR P. aeruginosa strains.
K. Rolston, None
I. Raad, UT MD Anderson Cancer Center: Shareholder , Licensing agreement or royalty
Novel Anti-Infective Technologies LLC: Shareholder , Licensing agreement or royalty