In vitro and in vivo antibacterial activities of ME1207, a new oral cephalosporin

Abstract

ME1207 (pivaloyloxymethyl ester of ME1206) is a new oral cephalosporin. ME1206 is (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)- acetamido]-3-[(Z)-2-(4-methylthiazol-5-yl)-ethyl]-cephem-4-carboxy lic acid. The susceptibilities of about 1,600 clinical isolates to ME1206 were determined by the agar dilution method. ME1206 showed a broad spectrum of activity against gram-positive and gram-negative bacteria. ME1206 was more active than cefaclor, T-2525, and cefixime against Staphylococcus aureus and Staphylococcus epidermidis. Against gram-negative bacteria, the activity of ME1206 was comparable with that of T-2525, but ME1206 was less active than cefixime. Against Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae, ME1206 had high activity (MIC, less than or equal to 0.05 microgram/ml). ME1206 was stable against various beta-lactamases, except beta-lactamases from Providencia rettgeri, Pseudomonas cepacia, and Escherichia coli W3630 (Rms213). The 50% effective doses of ME1207 after oral administration against systemic infections in mice were comparable with those of T-2588 against gram-negative bacteria and about one-fourth that of T-2588 against Staphylococcus aureus Smith.

beta-Lactamase stability and in vitro activity of oral cephalosporins against strains possessing well-characterized mechanisms of resistance

“…Six of seven isolates of the Enterobacteriaceae expressing an inducible, class I cephalosporinase were susceptible to ce- DISCUSSION The greater resistance of the newer oral cephalosporins to hydrolysis by a broad array of 3-lactamases was clearly demonstrated in this study. This confirms and expands upon previous findings of other investigators (1,3,4,6,15,16,19,26,27,29). From these data on P-lactamase stability, drug permeation, and induction of 3-lactamases, it is possible to explain differences in antimicrobial spectrum and potency among these oral cephalosporins.…”

“…Rather, it appeared to result from the high affinity of the drug for target enzymes. There has recently been intense activity in the development of new orally absorbable cephalosporins. Some of these compounds are directly absorbable in their active forms (2,6,7,10,11,13,16,28,30), while others are esters which must be enzymatically cleaved to their active forms after absoi-ption (3,5,9,17,18,20,27,29). Many of these newer compounds possess expanded antimicrobial spectra compared with spectra of older oral cephalosporins, which is thought to be due in large part to a diminished susceptibility to hydrolysis by 1-lactamases (1-6, 8, 9, 15-17, 19-21, 26, 27, 29).…”

Increasing Prevalence of Ampicillin- Resistant, Non-Beta-Lactamase-Producing Strains of <i>Haemophilus influenzae</i> in Children in Japan

“…All ß-lactamase-producing strains thus were ampicillin resistant (ampicillin MICs of 14 Ìg/ml). Although 35 ß-lactamase-negative strains were ampicillin-susceptible (MICs, &0.5 Ìg/ml), 28 ß-lactamase-negative strains (44.4% of all ß-lactamase-negative isolates) Chemotherapy 1999;45: [15][16][17][18][19][20][21] Seki/Kasahara/Ohta/Ohta/Saikawa/ Sumita/Yachie/Fujita/Koizumi …”

In vitro activity of LJC10,627, a new carbapenem antibiotic with high stability to dehydropeptidase I

“…13-Lactamase assays. 1-Lactamases from various strains were prepared by a previously described method (10). The stability of each compound for various P-lactamases was determined by a spectrophotometric assay (11).…”