Mecillinam Activity Compared to Ampicillin, Trimethoprim/Sulfamethoxazole, Ciprofloxacin and Nitrofurantoin against Urinary Tract Isolates of Gram-Negative Bacilli

Abstract

Recent Canadian, American and European studies have reported increased ampicillin and trimethoprim/sulfamethoxazole resistance among urinary tract isolates of Escherichia coli. This trend suggests that a reevaluation of first- and second-line therapies for the treatment of community-acquired urinary tract infections is necessary. Mecillinam, a β-lactam with preferential activity against gram-negative penicillin binding protein 2 (unlike other β-lactams which preferentially bind gram-negative penicillin binding proteins 1a, 1b or 3), may offer clinically significant activity against ampicillin-resistant and trimethoprim/sulfamethoxazole-resistant E. coli. To test this assertion, the activity of mecillinam was compared with ampicillin, trimethoprim/sulfamethoxazole, nitrofurantoin and ciprofloxacin against 258 consecutive gram-negative urinary tract isolates collected at a Canadian tertiary care hospital. Mecillinam demonstrated significantly better activity than ampicillin and trimethoprim/sulfamethoxazole and significantly less activity than ciprofloxacin and nitrofurantoin against the 258 isolates tested. Against E. coli isolates specifically, mecillinam was significantly more active than ampicillin and trimethoprim/sulfamethoxazole (p < 0.001) and as active as ciprofloxacin and nitrofurantoin. Mecillinam was active against 91.9% of ampicillin-resistant E. coli and 95.9% of trimethoprim/sulfamethoxazole-resistant E. coli. We conclude that mecillinam should be reevaluated for potential use in the treatment of community-acquired urinary tract infections.