Development of beta-lactam resistance and increased quinolone MICs during therapy of experimental Pseudomonas aeruginosa endocarditis.
نویسندگان
چکیده
The in vivo efficacies of pefloxacin, a new fluoroquinolone, and amikacin-ceftazidime were compared in 50 rabbits with experimental aortic endocarditis caused by Pseudomonas aeruginosa. Animals were randomly chosen to receive 4 or 10 days of no therapy (controls), pefloxacin (40 mg/kg [body weight] per day, intramuscularly [i.m.]), or amikacin (30 or 80 mg/kg per day, i.m.)-ceftazidime (150 mg/kg per day, i.m.). Pefloxacin and both amikacin regimens significantly reduced vegetation bacterial densities compared with controls at days 4 and 10 of treatment (P less than 0.0005). By day 10 of therapy, between 33 and 40% of vegetations from amikacin-ceftazidime recipients contained ceftazidime-resistant bacteria (MICs, greater than 25 micrograms/ml); nitrocefin agar overlay confirmed that these ceftazidime-resistant variants were constitutive overproducers of beta-lactamase. At therapy days 4 and 10, approximately 30% of vegetations sampled from pefloxacin recipients contained bacteria for which pefloxacin MICs were four- to eightfold higher than the MIC for the parental strain used to initially induce endocarditis (MIC, 0.19 microgram/ml). These variants also exhibited increases in ciprofloxacin and ticarcillin MICs, as well as pleotropic resistance to chloramphenicol (but not to amikacin, ceftazidime, or tetracycline). Amikacin-ceftazidime, as well as pefloxacin, was effective in this model of aortic pseudomonal endocarditis. However, in vivo development of ceftazidime resistance and step-ups in pefloxacin MICs among intravegetation isolates were associated with inability to completely eradicate P. aeruginosa from aortic vegetations.
منابع مشابه
Efficacy of ciprofloxacin in experimental aortic valve endocarditis caused by a multiply beta-lactam-resistant variant of Pseudomonas aeruginosa stably derepressed for beta-lactamase production.
The emergence of multi-beta-lactam resistance is a limiting factor in treating invasive Pseudomonas infections with newer cephalosporins. The in vivo efficacy of ciprofloxacin, a new carboxy-quinolone, was evaluated in experimental aortic valve endocarditis caused by a strain of Pseudomonas aeruginosa which is stably derepressed for beta-lactamase production and is resistant to ceftazidime and ...
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The in vivo efficacies of amikacin, ceftazidime, and their combination were evaluated in experimental aortic valve endocarditis due to Pseudomonas aeruginosa. Eighty catheterized rabbits were infected with a P. aeruginosa strain susceptible to both amikacin and ceftazidime and then received no therapy (controls), amikacin (15 mg/kg per day), ceftazidime (100 mg/kg per day), or amikacin-ceftazid...
متن کاملRole of beta-lactamase in in vivo development of ceftazidime resistance in experimental Pseudomonas aeruginosa endocarditis.
Two ceftazidime-resistant variants of Pseudomonas aeruginosa (PA-48, PA-60), obtained from cardiac vegetations of rabbits with endocarditis receiving ceftazidime therapy, were studied for mechanisms of resistance. Both resistant variants were stably derepressed for the type Id beta-lactamase, which was ceftazidime inducible in the parental strain (PA-96) used to initially infect the rabbits. Th...
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ورودعنوان ژورنال:
- Antimicrobial agents and chemotherapy
دوره 32 2 شماره
صفحات -
تاریخ انتشار 1988