Comparable evaluation of orally active beta-lactam compounds in ampicillin-resistant gram-positive and gram-negative rods: role of beta-lactamases on resistance

The antibacterial activity of the recently developed cephems cefixime and cefetamet-pivoxyl was evaluated in 408 gram-positive and gram-negative rods, all isolated recently from clinical specimens, and compared to that of other orally active agents such as ampicillin, amoxycillin + clavulanic acid, cefaclor, cefuroxime-axetil and to ceftriaxone. With regard to ampicillin-resistant Enterobacteriaceae ceftriaxone proved to be the most active agent, followed by cefixime and cefetamet, whereas cefuroxime was less active. Cefaclor and amoxycillin + claculanic acid were active against ampicillin-resistant Escherichia coli, Klebsiella pneumoniae, and Proteus ssp. isolates. All beta-lactam compounds exhibited poor activity against Acinetobacter anitratus isolates, but were highly active against Haemophilus influenzae with the exception of cefaclor. Both cefixime and cefetamet were poorly active against Staphylococcus aureus, but highly active against beta-hemolytic streptococci. Moreover, both compounds remained unaffected by the production of plasmid-mediated beta-lactamases such as the TEM or OXA enzymes. Resistance to both agents was observed in Enterobacteriaceae that produced large amounts of chromosomally mediated enzymes; their affinity to the class I enzyme from Enterobacter cloacae was somewhat lower than that of other third-generation cephalosporins. However, in contrast with these agents breakdown of cefixime and cefetamet by a class IIIa enzyme form Proteus vulgaris was marginal. In methicillin-resistant S. aureus isolates there was a complete cross-resistance between all beta-lactam compounds included in this study.