In-vitro activity of Sch 34343 against Gram-negative bacteria producing characterized beta-lactamases

The activity of Sch 34343 against 13 strains producing large amounts of characterized beta-lactamases was compared with that of imipenem, latamoxef (moxalactam), aztreonam and other third-generation cephalosporins. Sch 34343, like imipenem, was active against all strains, including many resistant to all other beta-lactams. MICs of Sch 34343 determined for 16 different inocula were rarely increased even at very high inocula. Sch 34343 was rapidly bactericidal against Escherichia coli TEM-2, Enterobacter agglomerans (with an induced beta-lactamase) and two strains of Bacteroides fragilis with highly active cephalosporinases. Like cefoxitin, Sch 34343 was only slowly inactivated by concentrated crude penicillinases which inactivated cefotaxime within 1 h. Sch 34343 was even more stable to cephalosporinases than was cefoxitin. Stability of the antibiotics to the different beta-lactamases was also determined by pre-incubating them with dilutions of the beta-lactamases before determination of MICs against E. coli 25922. Very large amounts of all enzymes were required to increase the MICs significantly for Sch 34343 and imipenem. These results indicate the good stability of Sch 34343 to beta-lactamases.