Effects of combination of benzylpenicillin and fosfomycin on penicillin-resistant Streptococcus pneumoniae.
The in vitro activity of benzylpenicillin in combination with fosfomycin against 51 clinical isolates of penicillin-resistant Streptococcus pneumoniae [minimal inhibitory concentrations (MICs) of benzylpenicillin > or = 0.5 mg/liter] was investigated. The fractional inhibitory concentration (FIC) index using the checkerboard method ranged from 0.38 to 0.75 (mean: 0.63). A synergy was also demonstrated in the killing curve on S. pneumoniae TW-1303 (MIC of benzylpenicillin, 2 mg/liter; MIC of fosfomycin, 32 mg/liter: FIC index, 0.38). Fosfomycin inhibited the production of all penicillin-binding proteins (PBP) except PBP 2B of S. pneumoniae TW-1303 and it decreased that of PBP 2B when it was combined with benzylpenicillin. These results suggest that the combination of benzylpenicillin and fosfomycin could be considered as the alternative treatment of penicillin-resistant pneumococcal infections.
Kikuchi
K
K
Department of Medicine, Tokyo Women's Medical College, Japan.
Totsuka
K
K
Shimizu
K
K
Ishii
T
T
Yoshida
T
T
Orikasa
Y
Y
D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D005578:Fosfomycin / Q000494:pharmacology*; D006602:Hexosyltransferases; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D010400:Penicillin G / Q000494:pharmacology*; D010403:Penicillin Resistance; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000494:pharmacology*; D010458:Peptidyl Transferases; D013296:Streptococcus pneumoniae / Q000187:drug effects*
D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D005578:Fosfomycin; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D010400:Penicillin G