Bactericidal Activity, Absence of Serum Effect, and Time-Kill Kinetics of Ceftazidime-Avibactam against β-Lactamase-Producing Enterobacteriaceae and Pseudomonas aeruginosa
Autor: | Chris Celeri, Wright W. Nichols, M. A. Gómez, Tiffany R. Keepers, Kevin M. Krause |
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Rok vydání: | 2014 |
Předmět: |
Avibactam
Serum albumin Ceftazidime Microbial Sensitivity Tests medicine.disease_cause beta-Lactam Resistance Microbiology chemistry.chemical_compound Enterobacteriaceae medicine Humans Experimental Therapeutics Pharmacology (medical) Serum Albumin Pharmacology Minimum bactericidal concentration Dose-Response Relationship Drug biology Pseudomonas aeruginosa Ceftazidime/avibactam biology.organism_classification Anti-Bacterial Agents Drug Combinations Kinetics Infectious Diseases chemistry biology.protein Antibacterial activity Azabicyclo Compounds medicine.drug |
Zdroj: | Antimicrobial Agents and Chemotherapy. 58:5297-5305 |
ISSN: | 1098-6596 0066-4804 |
Popis: | Avibactam, a non-β-lactam β-lactamase inhibitor with activity against extended-spectrum β-lactamases (ESBLs), KPC, AmpC, and some OXA enzymes, extends the antibacterial activity of ceftazidime against most ceftazidime-resistant organisms producing these enzymes. In this study, the bactericidal activity of ceftazidime-avibactam against 18 Pseudomonas aeruginosa isolates and 15 Enterobacteriaceae isolates, including wild-type isolates and ESBL, KPC, and/or AmpC producers, was evaluated. Ceftazidime-avibactam MICs (0.016 to 32 μg/ml) were lower than those for ceftazidime alone (0.06 to ≥256 μg/ml) against all isolates except for 2 P. aeruginosa isolates (1 bla VIM -positive isolate and 1 bla OXA-23 -positive isolate). The minimum bactericidal concentration/MIC ratios of ceftazidime-avibactam were ≤4 for all isolates, indicating bactericidal activity. Human serum and human serum albumin had a minimal effect on ceftazidime-avibactam MICs. Ceftazidime-avibactam time-kill kinetics were evaluated at low MIC multiples and showed time-dependent reductions in the number of CFU/ml from 0 to 6 h for all strains tested. A ≥3-log 10 decrease in the number of CFU/ml was observed at 6 h for all Enterobacteriaceae , and a 2-log 10 reduction in the number of CFU/ml was observed at 6 h for 3 of the 6 P. aeruginosa isolates. Regrowth was noted at 24 h for some of the isolates tested in time-kill assays. These data demonstrate the potent bactericidal activity of ceftazidime-avibactam and support the continued clinical development of ceftazidime-avibactam as a new treatment option for infections caused by Enterobacteriaceae and P. aeruginosa , including isolates resistant to ceftazidime by mechanisms dependent on avibactam-sensitive β-lactamases. |
Databáze: | OpenAIRE |
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