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Comparative in vitro activity of piribenicillin, ticarcillin, and carbenicillin against Pseudomonas aeruginosa
Abstract:
Pirbenicillin, a semisynthetic penicillin, showed greater in vitro activity against 68 recent isolates of Pseudomonas aeruginosa than did ticarcillin or carbenicillin. The median minimum inhibitory concentration of each of these three compounds, respectively, was 3.1, 12.5, and 25 mug/ml when a 10(-4) dilution of an overnight culture (about 10(5) colony-forming units [CFU]/ml) was used as inoculum, but these differences were less striking when larger inocula were used: at 10(7) CFU/ml these values were 6.25, 12.5, and 50 mug/ml, and at 10(8) to 10(9) CFU/ml these values were 50, 50, and 100 mug/ml. All three compounds showed greater inhibitory activity at pH 6 than at pH 8. This pH effect was greatest with pirbenicillin, for 6.25 mug of pirbenicillin per ml inhibited 7, 11, and 57% of the strains at pH 6, 7, and 8, respectively; these values were 4, 4, and 11% with ticarcillin and 0, 0, and 7% with carbenicillin. At sufficient inhibitory concentrations, the rates of bacterial killing of the three compounds were similar. The observed differences in anti-pseudomonad activity were not due to differences in stability to pseudomonad beta-lactamases, but all three compounds were more stable than were cefazolin, cephaloridine, and benzylpenicillin.
Insights
Pirbenicillin demonstrates superior in vitro activity against Pseudomonas aeruginosa compared to ticarcillin and carbenicillin, particularly at lower bacterial concentrations and acidic pH levels. This enhanced efficacy is not linked to beta-lactamase stability.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Pseudomonas aeruginosa is a significant opportunistic pathogen.
- Penicillins are crucial antibiotics for treating bacterial infections.
- Understanding the comparative efficacy of different penicillins against P. aeruginosa is clinically important.
Purpose of the Study:
- To compare the in vitro activity of pirbenicillin, ticarcillin, and carbenicillin against Pseudomonas aeruginosa isolates.
- To evaluate the influence of inoculum size and pH on the activity of these antibiotics.
- To assess the stability of these penicillins against Pseudomonas aeruginosa beta-lactamases.
Main Methods:
- In vitro susceptibility testing of 68 Pseudomonas aeruginosa isolates.
- Determination of minimum inhibitory concentrations (MICs) using varying inoculum sizes (10^5 to 10^9 CFU/ml).
- Evaluation of antibiotic activity at different pH values (pH 6 and pH 8).
Main Results:
- Pirbenicillin exhibited lower median MICs than ticarcillin and carbenicillin across different inoculum sizes.
- Antibacterial activity for all three penicillins was greater at pH 6 than pH 8, with pirbenicillin showing the most pronounced pH-dependent effect.
- Bacterial killing rates were similar for all three compounds at inhibitory concentrations.
- Pirbenicillin, ticarcillin, and carbenicillin demonstrated greater stability against Pseudomonas aeruginosa beta-lactamases compared to cefazolin, cephaloridine, and benzylpenicillin.
Conclusions:
- Pirbenicillin shows enhanced in vitro activity against Pseudomonas aeruginosa compared to ticarcillin and carbenicillin.
- The efficacy of these penicillins is influenced by inoculum size and pH.
- Pirbenicillin's improved activity is not attributed to increased stability against Pseudomonas beta-lactamases.
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