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 multiple other beta-lactam agents. A total of 51 catheterized rabbits with aortic catheters in place were infected with this strain and then received no therapy (controls), ceftazidime (75 mg/kg per day), or ciprofloxacin (80 mg/kg per day). Ciprofloxacin sterilized all blood cultures and significantly lowered vegetation densities of P. aeruginosa by day 2 of treatment versus controls (P less than 0.0005) and animals receiving ceftazidime (P less than 0.0005). This beneficial effect of ciprofloxacin was also noted on therapy days 6 and 11. Ciprofloxacin rendered most vegetations (85%) culture negative over the 11-day treatment period and achieved bacteriologic cure in 73% of animals (P less than 0.0005 versus other therapy groups). Ciprofloxacin prevented bacteriologic relapse at 6 days posttherapy. No ciprofloxacin resistance was detected among Pseudomonas isolates from cardiac vegetations. Ciprofloxacin warrants further evaluation in vivo versus multi-drug-resistant gram-negative bacillary infections.
D000818:Animals; D001021:Aortic Valve; D002442:Ceftazidime / Q000097:blood / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000097:blood / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial; D004697:Endocarditis, Bacterial / Q000188:drug therapy*; D005260:Female; D006349:Heart Valve Diseases / Q000188:drug therapy; D011552:Pseudomonas Infections / Q000097:blood / Q000188:drug therapy*; D011817:Rabbits
D002939:Ciprofloxacin; D002442:Ceftazidime