Telithromycin in vitro

Transcription

1 in vitro Telithromycin in vitro MBCMIC Staphylococcus aureus Enterococcus faecalis0 Streptococcus pneumoniae Haemophilus influenzae telithromycin MIC MBC erythromycin Aclarithromycin azithromycin josamycin S. aureus E. faecalis MBC0MIC0 MBC0MIC0 S. pneumoniae H. influenzae MBC0MIC0 MBC0MIC0 S. aureus E. faecalis S. pneumoniae H. influenzae S. aureuss. pneumoniae H. influenzae S. aureus Smith MICMIC S. pneumoniae DP MIC MIC H. influenzae ATCC MICMIC S. pneumoniae DP H. influenzae ATCC S. aureus Smith H. influenzae ATCC Key words: telithromycinmbc Telithromycin Streptococcus pneumoniae Haemophilus influenzae Mollaxella catarrhalis Staphylococcus aureus Enterococcus faecalis S. pneumoniae H. influenzae MIC MBC MIC MBC S. aureuss. pneumoniae H. influenzae erythromycin Aclarithromycin azithromycin josamycin I.... mgml MIC MBC MIC MIC0 S. aureus S. pneumoniae E. faecalis 0 H. influenzae S. aureus SmithS. pneumoniae DP H. influenzae

2 Table Bactericidal activity of telithromycin and other macrolides against clinical isolates Antibi- Range otics MIC MBC MIC0MBC0 MIC0MBC0 Staphylococcus aureus [] Streptococcus pneumoniae [] Enterococcus faecalis [0] Haemophilus influenzae [] 0 0 MIC: minimum inhibitory concentrationµgml, MBC: minimun bactericidal concentrationµgml The MIC was determined by the broth microdilution method. For MBC determination, µl aliquot of each of bacterial suspensions for MIC determination was applied to an antibioticfree agar plate, which was incubated for 0 h. The lowest concentration of antibiotic giving none colonies was recorded as the MBC. : telithromycin, : erythromycin A, : clarithromycin, : azithromycin, : josamycin ATCC S. aureus Ca Mg MullerHintonMHDifcoHB S. pneumoniae E. faecalis HB H. influenzae ml DifcomgmL HB S. aureus Smith MH S. pneumoniae DP MH H. influenzae ATCC Difco Brain heart infusion brothbhidifco MIC MBC MIC. mgml 0.00 ml U Corning 00L S. aureus S. pneumoniae, E. faecalis H. influenzae MH 0. McFarland 0 L 0 CFUmL 0 MIC MBC MIC 0 L Nunc 0 MBC. MIC0 MIC0 MBC0 MBC0 MBC0MIC0 MBC0MIC0 0 L 0 CFUmL.

3 in vitro ml MIC 0. ml 0 0 L BSGbuffered saline with gelatin; NaCl. g KHPO 0. gnahpo 0. ggelatin 0. g ml 0 ml CFUmL logcfuml logcfuml log CFUmL log CFUmL II S. aureus MBC0 MIC0 MBC0 MIC0 S. aureus MIC MBC ml Table S. pneumoniae MBC0 MBC0 MIC0 MIC0 S. pneumoniae MIC MBC ml Table E. faecalis MBC0 MIC0 MBC0 MIC0 E. faecalis MIC MBC Telithromycin 0 Erythromycin A /MIC /MIC MIC0.g/mL /MIC /MIC MICg/mL Viable bacterial countlog CFU/mL 0 MIC MIC Clarithromycin /MIC 0 MIC MIC Azithromycin /MIC /MIC MIC /MIC MICg/mL MIC MICg/mL MIC MIC 0 0 Incubation timeh Fig Killing curves of telithromycin and other macrolides against Staphylococcus aureus Smith.

4 0 Telithromycin 0 Erythromycin A /MIC /MIC /MIC /MIC MIC0.0g/mL Viable bacterial countlog CFU/mL 0 MIC0.0g/mL MIC MIC Clarithromycin 0 /MIC /MIC MIC0.0g/mL MIC MIC MIC Azithromycin /MIC /MIC MIC0.g/mL MIC 0 MIC MIC 0 Incubation timeh Fig Killing curves of telithromycin and other macrolides against Streptococcus pneumoniae DP. ml Table H. influenzae MBC0 MIC0 MBC0 MIC0 H. influenzae MIC MBC ml Table S. aureus Smith MICMIC logcfuml MIC MIC. log CFUmL Fig S. pneumoniaedp MIC MIC logcfuml MIC logcfuml logcfu ml MIC Fig H. influenzae ATCC MIC MIC MIC MIC MIC MIC MIC Fig III MIC MBC S. aureus E. faecalis S. pneumoniae H. influenzae S. aureus E. faecalis MBC0 MIC0 MBC0 MIC0 MBC0 MIC0 MBC0

5 in vitro 0 Telithromycin 0 Erythromycin A /MIC /MIC /MIC /MIC Viable bacterial countlog CFU/mL 0 MIC MICg/mL MIC Clarithromycin /MIC /MIC MICg/mL MIC MIC 0 MICg/mL MIC MIC Azithromycin /MIC /MIC MICg/mL MIC MIC 0 0 Incubation timeh Fig Killing curves of telithromycin and other macrolides against Haemophilus influenzae ATCC. MIC0 S. pneumoniae H. influenzae MBC0 MBC0 MIC0 MIC0 S. aureus E. faecalis S. pneumoniae H. influenzae S. aureus E. faecalis MBC ml ml S. aureuss. pneumoniae H. influenzae S. aureus Smith MIC S. pneumoniae DP H. influenzae ATCC MIC MBCMIC S. aureus S. pneumoniae H. influenzae S. pneumoniae H. influenzae S. aureus Smith H. influenzae ATCC logcfuml S. pneumoniae H. influenzae MIC S. pneumoniae H. influenzae

6 Bryskier A: New research macrolides and ketolides since. Expert Opinion on Investigational Drugs : Jones R NBiedenbach D J: Antimicrobial activity of RUanewketolide. Diagn Microbiol Infect Dis : Biedenbach D JBarrett M SJones R N: Comparative antimicrobial activity and killcurve investigations of novel ketolide antimicrobial agents HMR 00 and HMR tested against Haemophilus influenzae and Moraxella catarrhalis strains. Diagn Microbiol Infect Dis : Pankuch G AVisalli M AJacobs M Ret al.: Susceptibilities of penicillin and erythromycin susceptible and resistant pneumococci to HMR RU a newketolidecompared with susceptibilities to other agents. Antimicrob Agents Chemother : 0 Reinert R RBryskier ALutticken R: In vitro actibities of the new ketolide antibiotics HMR 00 and MHR against Streptococcus pneumoniae in Germany. Antimicrob Agents Chemother : 0 : Telithromycin in vitro in vitro S : 00 : MIC Chemotherapy : 00 0 : MIC Chemotherapy : In vitro bactericidal activity of telithromycin MBCMIC ratio and killing curve Susumu AraiHiroki OkamotoKeiko Noguchi Kaoru Ushiba and Masafumi Yaguchi PharmacologyLead OptimizationDrug Innovation & Approval DivisionAventis Pharma Ltd., MinamidaiKawagoeSaitamaJapan MBCMIC ratio of telithromycinfor clinical isolates of Staphylococcus aureus strains Enterococcus faecalis0 strainsstreptococcus pneumoniae strainsand Haemophilus influenzae isolatesin Japan was compared with those of erythromycin Aclarithromycin azithromycinand josamycinexisting macrolide antibiotics. As a resultmbc0mic0 and MBC0MIC0 ratios of all compounds tested for S. aureus and E. faecalis were more than but the ratios for S. pneumoniae and H. influenzae were less than. Thereforethis study suggested that had bacteriostatic effects against S. aureus and E. faecalisbut bactericidal effect against S. pneumoniae and H. influenzaein additionthe bactericidal activity of against standard strains of S. aureuss. pneumoniae and H. influenzae was compared with those of and on the basis of their killing curves. Against S. aureus Smith was slightly less potent than. Howeveras in the case of and inhibited the proliferation at MIC and showed mild bactericidal activity at MIC. Against S. pneumoniae DP inhibited the growth at the concentration lower than MIC and showed bactericidal activity at the MIC or concentration higher than MIC as observed in other reference drugs. Against H. influenzae ATCC inhibited the growth at the MIC and showed bactericidal activity at the concentration higher than MIC. showed strong shortterm bactericidal activity in comparison with and especially against S. pneumoniae DP and H. influenzae ATCC. Furthermoremarked regrowth as observed in S. aureus and H. influenzae ATCC in case of and was not observed in.