Efficacy of a novel tetracycline derivative, glycylcycline, against penicillin-resistant Streptococcus pneumoniae in a mouse model of pneumonia.
The MIC90 of glycylcycline (< or =0.06 mg/L) against 55 strains of Streptococcus pneumoniae was 100-fold lower than that of minocycline or tetracycline. In a mouse model of penicillin-resistant S. pneumoniae (PRSP) pneumonia, glycylcycline (10 mg/kg) decreased bacterial counts in the lungs from 10(6) cfu to <10(2) cfu, whereas no apparent reduction of bacterial numbers was observed with minocycline or penicillin G. Pharmacokinetic studies showed that the half-life and area under the curve of glycylcycline were superior to those of minocycline and penicillin G in the lungs. These results show a preferential distribution of glycylcycline in the lungs and potent in vivo bactericidal activity in PRSP pneumonia.
Murakami
K
K
Department of Microbiology, Toho University School of Medicine, 5-21-16 Ohmori-nishi, Ohta-ku, Tokyo 143-8540, Japan.
Tateda
K
K
Matsumoto
T
T
Miyazaki
S
S
Yamaguchi
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D008826:Microbial Sensitivity Tests / Q000379:methods; D008911:Minocycline / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D010400:Penicillin G / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D010406:Penicillins / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D013752:Tetracycline / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D010406:Penicillins; D013752:Tetracycline; D008911:Minocycline; D010400:Penicillin G