Synergy of Mecillinam, a Beta-Amidinopenicillanic Acid Derivative, Combined with Beta-Lactam Antibiotics

Abstract

Mecillinam, a β-amidinopenicillanic acid derivative, was combined with ampicillin, amoxicillin, carbenicillin, cephalothin, cefamandole, and cefoxitin and tested against most members of the Enterobacteriaceae and Pseudomonas . Synergy was demonstrated with selected isolates of most of the organisms tested. Isolates highly susceptible to mecillinam (minimum inhibitory concentration, <0.8 μg/ml) were not synergistically inhibited by addition of another β-lactam antibiotic. Synergy of mecillinam and a β-lactamase-resistant penicillin, cloxacillin, was demonstrated. In media of osmolality >10 mOsm or of conductivity >6 mS, mecillinam and β-lactam antibiotics showed synergy in most instances, whereas at low osmolality and conductivity the activity of mecillinam is so great that synergy cannot be demonstrated. The proportion of mecillinam to β-lactam antibiotic that will be synergistic ranged from 100:1 to 1:1 to 1:100. Mecillinam did not increase the activity, minimum inhibitory concentration or minimum bactericidal concentration values, of β-lactam compounds against streptococci, staphylococci, clostridia, listeria, or bacteroides. Synergy was not demonstrated with combinations of mecillinam and aminoglycosides (kanamycin, gentamicin, tobramycin, amikacin), chloramphenicol, tetracycline, or polymyxins.