2022 Volume 80 Issue 7 Pages 676-690
Antimicrobial resistance (AMR) raises a difficult challenge in achieving universal health coverage. Antibiotic-resistant Streptococcus pneumoniae strains may cause infections that fail to respond to antimicrobial therapy. Clindamycin, an orally active derivative of natural lincomycin, is effective against Gram-positive bacteria including S. pneumoniae, but is not active enough against resistant bacteria of S. pneumoniae possessing constitutive erm gene. Novel chemical modifications of lincomycin at the C-6 and C-7 positions were exhaustively performed to explore useful derivatives which are effective against resistant S. pneumoniae with erm gene. Two groups among them exhibited potent activities against resistant S. pneumoniae with erm gene. The first group was 7(S)-S-1,3,4-thiadiazole derivatives and the second group was 7(S)-S-phenyl derivatives. Several derivatives in the second group exhibited potent in vitro activities against 60 clinical isolates of S. pneumoniae including susceptible strains and resistant strains with erm and/or mef genes, and two of them exhibited strong therapeutic effects in rat in vivo models.
