Microbiological properties of sulbactam combined with ampicillin

Several in vitro parameters of sulbactam combined with ampicillin (Sbt/Amp) were studied in order to evaluate and compare its microbiological properties with those of beta-lactamase stable beta-lactams (ceftriaxone, cefamandole, cefoxitin). The intrinsic activity of Sbt/Amp was satisfactory and comparable to that of other beta-lactams and no significant difference was observed against beta-lactamase producing or non-producing bacteria. Besides, it was determined that sulbactam, when combined with ampicillin at different ratios (1:2, 5:1), with and without preincubation (60 min) reduces the hydrolysis of ampicillin determined by ten different standard beta-lactamases. The hydrolysis rates of ampicillin become as low as those of cefoxitin, cefamandole and ceftriaxone, which are beta-lactamase stable cephalosporins. In fact, all the antibiotics under examination were slightly hydrolyzed by several beta-lactamases, but such slight hydrolysis did not affect the antibacterial activity against beta-lactamase producing bacteria. About 50% of non-beta-lactamase producing bacteria (18 strains of different bacterial species) produced an inducible beta-lactamase after ten daily subcultures with sub-inhibitory concentrations of each antibiotic, but minimum inhibitory concentrations (MICs) of Sbt/Amp never increased after stimulation in contrast with other drugs whose MICs were much higher in consequence of this procedure. Finally, no spontaneous resistant mutant to Sbt/Amp was detected, but several mutants appeared in response to the other drugs. Sulbactam makes ampicillin as effective as beta-lactamase stable cephalosporins and its use does not determine an increase of resistance or selection of resistant mutants.