Abstract:
:The susceptibility of a group of beta-lactamase-producing and drug-resistant Gram-positive and Gram-negative organisms was tested against a novel cephalosporin (Ro 48-8391) alone and in combination with two bridged carbacephem beta-lactamase inhibitors (Ro 48-5545 or Ro 48-8724) and compared with that of ceftriaxone, ceftazidime, and cefepime (representative "third- and fourth-generation" cephalosporins), imipenem, and a combination of piperacillin and tazobactam. Five hundred and one selected clinical isolates were tested using the reference broth microdilution method (National Committee for Clinical Laboratory Standards). Ro 48-8391 has a spectrum of activity and potency most similar to ceftriaxone but with improved activity against Gram-positive species. The two beta-lactamase inhibitors, Ro 48-5545 and Ro 48-8724, have modest antimicrobial activity. When combined with Ro 48-8391, the beta-lactamase inhibitor Ro 48-8724 was superior to the combination of Ro 48-8391 and Ro 48-5545 in spectrum and enzyme inhibition against extended spectrum beta-lactamase enzyme-producing Escherichia coli and Klebsiella pneumoniae, and against Enterobacteriaceae with "stably derepressed" Bush-Jacoby-Medeiros gr 1 enzymes (ceftazidime-resistant Enterobacter and Citrobacter). Ro 48-5545 and Ro 48-8724 appear to be promising beta-lactamase inhibitors with potential application against chromosomal- and plasmid-mediated enzymes. Ro 48-8391, although superior to some currently available "third-generation" cephems, was not a well-matched active codrug because of limited activity against several commonly isolated species of clinically important bacteria. Further efforts are necessary to find a penicillin or cephem with activity more complementary to that of the tested beta-lactamase inhibitors and the Ro 48-8391 compound could be focused for therapeutic use in serious streptococcal infections.
journal_name
Diagn Microbiol Infect Disjournal_title
Diagnostic microbiology and infectious diseaseauthors
Jones RN,Marshall SA,Varnam DJdoi
10.1016/s0732-8893(98)00045-5subject
Has Abstractpub_date
1998-10-01 00:00:00pages
85-94issue
2eissn
0732-8893issn
1879-0070pii
S0732-8893(98)00045-5journal_volume
32pub_type
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