<I>In vitro</I> and <I>in vivo</I> antibacterial activity of S-1108, a new oral cephem antibiotic

In this study we tested the in vitro antibacterial activity of S-1006, the parent compound of S-1108, and the in vivo therapeutic efficacy of S-1108, a new orally active ester derivative of S- 1006, against experimental mouse infections in comparison with cefaclor (CCL), cefuroxime (CXM), cefixime (CFIX), cefteram (CFTM), FK-482 and BMY-28100.<BR>S-1006 had a broad antibacterial spectrum against gram-positive and gram-negative bacteria and it's antibacterial activity was almost equal to that of CXM against gram-positive bacteria, and superior to those of CCL and BMY-28100 and equal to that of CFTM against gram-negative bacteria.<BR>In the sensitivity distribution of clinically isolated strains, S-1006 showed weak activity against MRSA and Enterococcus spp. of gram-posittive bacteria, while being similar to CFTM and CXM and superior to CCL and CFIX against Streptococcus spp. The activity of S-1006 against gram-negative bacteria was equal to that of CFTM and superior to that of CCL.<BR>The activity of S-1006 was largely unaffected by the type of culture medium, inoculum size or addition of horse serum, but its activity against S. aureus was enhanced in acidic media.<BR>S-1006 showed dose-related bactericidal activity against all the bacteria tested.<BR>In morphological examinations by phase-contrast microscopy, S-1006 induced the formation of filamentous cells in E. coli KC-14, K. pneumoniae KC-1 and S. marcescens T-55. In one strain of the three P. mirabilis strains tested, S-1006 induced spheroplastlike structures, but did not result in the production of filamentous forms of the bacteria. On the other hand, CFTM and CCL gave rise to filamentous infections in mice, and the therapeutic effects of S-1108 were superior to those of CFTM-PI against gram-positive bacteria and almost equal to those of CCL and BMY-28100 against E. coli and K. pneumoniae of gramnegative bacteria. In S. marcescens T-55 infections in mice, S-1108 was similar to CFTM and FK-482 and superior to CCL and CXM-AX. S-1108 and CXM-AX showed good therapeutic efficacies against A. caloaceticus AC-54, but no other antibiotics tested showed any effects.<BR>In an experimental pulmonary infection with K. pneumoniae B-54 in mice, the therapeutic efficacy of S-1108 was inferior to that of CFIX and similar to that of CFTM-PI.