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[Pseudomonas aeruginosa: acquired in vitro resistance to beta-lactams]
Abstract:
The development of resistance acquired in vitro to 5 semi-synthetic penicillins: carbenicillin, ticarcillin, azlocillin, mezlocillin, piperacillin and to 5 cephalosporins: cefotaxime, cefoperazone, moxalactam, cefsulodin and ceftazidime, was compared in 6 strains of Pseudomonas aeruginosa. The strains were selected on the basis of their phenotypic resistance: 3 were susceptible to all the betalactam antibiotics tested, 1 was resistant to carbenicillin and ticarcillin but remained susceptible to the others, 2 were susceptible to cefsulodin and ceftazidime but resistant to the others. The development of resistance was investigated by subsequent passages in liquid medium: up to 15 passages or up to an MIC of 4 096 mg/l for a penicillin or 512 mg/l for the cephalosporins. Irrespectively of the phenotypic resistance, for all cephalosorins the MIC became greater than or equal to 64 mg/l and very often greater than or equal to 512 mg/l after 1 to 3 passages. For the penicillin susceptible strains very high MICs were obtained more rapidly with azlocillin and piperacillin (1-2 passages) than with carbenicillin or ticarcillin (5-9 passages). These results are not in favour of a monotherapy with betalactam antibiotics, especially cephalosporins, in the treatment of Pseudomonas aeruginosa infections, but suggest the preferential use of carbenicillin and especially ticarcillin for sensitive isolates.
Insights
Pseudomonas aeruginosa rapidly develops resistance to cephalosporins and newer penicillins in vitro. Carbenicillin and ticarcillin showed slower resistance development, suggesting their preferential use for sensitive Pseudomonas aeruginosa infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen known for developing antimicrobial resistance.
- Beta-lactam antibiotics, including penicillins and cephalosporins, are crucial for treating P. aeruginosa infections.
- Understanding the in vitro resistance development is vital for guiding effective therapeutic strategies.
Purpose of the Study:
- To compare the in vitro acquired resistance development to semi-synthetic penicillins and cephalosporins in Pseudomonas aeruginosa.
- To evaluate resistance patterns across P. aeruginosa strains with varying initial phenotypic resistance.
- To inform optimal antibiotic selection for P. aeruginosa infections.
Main Methods:
- Six strains of Pseudomonas aeruginosa with diverse resistance profiles were selected.
- In vitro resistance was assessed through serial passages in liquid medium.
- Minimum Inhibitory Concentrations (MICs) were determined for tested beta-lactam antibiotics.
Main Results:
- All tested cephalosporins induced rapid resistance (MIC ≥ 64 mg/l) within 1-3 passages, regardless of initial susceptibility.
- Penicillin-susceptible strains developed high-level resistance to azlocillin and piperacillin faster (1-2 passages) than to carbenicillin or ticarcillin (5-9 passages).
- Resistance development varied based on the specific beta-lactam antibiotic and P. aeruginosa strain characteristics.
Conclusions:
- Monotherapy with beta-lactam antibiotics, particularly cephalosporins, is not recommended for P. aeruginosa infections due to rapid resistance.
- Carbenicillin and especially ticarcillin may be preferred for treating P. aeruginosa infections in isolates sensitive to these agents.
- Further research into resistance mechanisms and combination therapies is warranted.