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Comparative in vitro interactions of ceftazidime, meropenem, and imipenem with amikacin on multiresistant Pseudomonas
E J Giamarellos-Bourboulis1, P Grecka, H Giamarellou
11st Department of Propedeutic Medicine, Athens University, Medical School, Greece.
Abstract:
To evaluate the possibility of an enhanced killing effect by ceftazidime, meropenem, or imipenem with amikacin 26 multiresistant Pseudomonas aeruginosa isolates, to nine anti-pseudomonal antimicrobials of diverse chemical classes were studied. A modified time-kill curve procedure was used with a 16 micrograms/ml concentration of each antimicrobial, i.e. within the range of their serum level; a total of 248 killing-curves were performed. Any > or = 2 log10 decrease of viable cell counts by a combination compared to the most active single agent was considered an adequate enhanced killing effect. The latter was found to be mainly expressed at 24 h of growth and involved 30-50% of the tested isolates. The above findings were independent of the MIC level to any individual beta-lactam or to amikacin. It is concluded that there is no difference between the activity of the ceftazidime and amikacin combination and those of meropenem or imipenem with amikacin on multiresistant P. aeruginosa.
Insights
Combining amikacin with ceftazidime, meropenem, or imipenem showed similar enhanced killing effects against multiresistant Pseudomonas aeruginosa. This combination therapy demonstrated effectiveness in 30-50% of tested isolates after 24 hours.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Multiresistant Pseudomonas aeruginosa poses a significant threat due to limited treatment options.
- Combination antibiotic therapy is explored to overcome antimicrobial resistance.
- Amikacin, ceftazidime, meropenem, and imipenem are critical agents for treating Pseudomonas aeruginosa infections.
Purpose of the Study:
- To assess the synergistic killing effect of amikacin combined with beta-lactam antibiotics (ceftazidime, meropenem, imipenem) against multiresistant Pseudomonas aeruginosa.
- To determine if specific beta-lactam and amikacin combinations offer enhanced antimicrobial activity.
- To evaluate the efficacy of these combinations at clinically relevant concentrations.
Main Methods:
- Utilized a modified time-kill curve assay to evaluate antimicrobial activity.
- Tested 26 multiresistant Pseudomonas aeruginosa isolates against nine anti-pseudomonal antimicrobials.
- Assessed combinations at a concentration of 16 µg/ml, simulating serum levels, performing 248 killing curves.
Main Results:
- Enhanced killing effect, defined as a ≥2 log10 decrease in viable cell counts compared to the most active single agent, was observed in 30-50% of isolates.
- This enhanced activity was primarily evident at 24 hours of incubation.
- The observed efficacy was independent of the minimum inhibitory concentration (MIC) of individual beta-lactams or amikacin.
Conclusions:
- Ceftazidime, meropenem, and imipenem combined with amikacin exhibit comparable enhanced killing effects against multiresistant Pseudomonas aeruginosa.
- No significant difference in activity was found between the ceftazidime-amikacin combination and the meropenem-amikacin or imipenem-amikacin combinations.
- These findings suggest that combinations of amikacin with different beta-lactams can be considered for treating infections caused by these challenging pathogens.
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