Comparative pharmacodynamics of telithromycin and clarithromycin with Streptococcus pneumoniae and Staphylococcus aureus in an in vitro dynamic model: focus on clinically achievable antibiotic concentrations.
To compare the pharmacodynamics of telithromycin and clarithromycin, killing kinetics of differentially susceptible Streptococcus pneumoniae and Staphylococcus aureus exposed to clinical doses of telithromycin and clarithromycin were studied in an in vitro dynamic model that simulates human pharmacokinetics. With S. pneumoniae, a bacterial strain-independent and antibiotic-independent relationship was delineated for the area between the control growth curve and the time-kill curve (ABBC) and the simulated ratio of the area under the curve (AUC) to minimum inhibitory concentration (MIC). Based on the ABBC-AUC/MIC relationship, a greater anti-pneumococcal effect of 800mg telithromycin compared with 2x500 mg clarithromycin was predicted for a hypothetical strain with MICs equal to the respective MIC50 values. Although telithromycin was less efficient against S. aureus, treatment for 3 days with telithromycin was not accompanied by a loss in susceptibility, whereas the enrichment of resistant staphylococci occurred with one of the two clarithromycin-treated strains.
Alferova
Irene V
IV
Department of Pharmacokinetics & Pharmacodynamics, Gause Institute of New Antibiotics, Russian Academy of Medical Sciences, 11 Bolshaya Pirogovskaya Street, Moscow 119021, Russia.
Vostrov
Sergey N
SN
Portnoy
Yury A
YA
Lubenko
Irene Y
IY
Zinner
Stephen H
SH
Firsov
Alexander A
AA
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D017291:Clarithromycin / Q000493:pharmacokinetics / Q000494:pharmacology*; D015169:Colony Count, Microbial; D024881:Drug Resistance, Bacterial; D048628:Ketolides / Q000493:pharmacokinetics / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000254:growth & development
D000900:Anti-Bacterial Agents; D048628:Ketolides; D017291:Clarithromycin; C106791:telithromycin