JAC Advance Access published online on September 30, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg437
© 2003 by The British Society for Antimicrobial Chemotherapy
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Brief report
1 Department of Pathology,
Case Western Reserve University and University Hospitals of Cleveland,
11100 Euclid Ave., Cleveland, OH 44106
* Corresponding author. E-mail: mrj6{at}po.cwru.edu.
Received 24 February 2003
; revised 1 July 2003
; accepted 5 August 2003
Post-antibiotic effects (PAE) and post-antibiotic sub-MIC
effects (PA-SME) of the ketolide telithromycin (HMR 3647) were determined
for 10 Gram-positive cocci with various macrolide resistance mechanisms, including
inducible and constitutive ribosomal methylase and macrolide efflux
resistance genes. Strains tested included four Streptococcus
pneumoniae, three Streptococcus pyogenes and
three Staphylococcus aureus. Telithromycin MICs
were 0.008-0.015 mg/L for pneumococci, 0.015-4.0
mg/L for S. pyogenes and 0.03 mg/L for staphylococci.
PAE were determined after exposure of strains at 10 x MIC
for 1 h. PA-SME were determined in the presence of 0.12x,
0.25x and 0.5x MIC
of the agent after the initial 1 h exposure period. The PAE of telithromycin
varied from 0.3 to 3.8 h; the PA-SME varied from 0.8 to 4.6 h, with
maximal PA-SME varying from 1.5 to 4.6 h. PAE tended to be shortest
for S. pyogenes (0.4-2.7 h) and S.
aureus (0.3-2.4 h), compared to 1.5-3.8 h
for S. pneumoniae. The duration of the PA-SME was
similar for the three species tested. The low MICs for many strains
as well as the PAE and PA-SME demonstrated in this study for telithromycin
show promise for increasing the dosing interval of this ketolide,
but will need verification by pharmacokinetic/pharmacodynamic and
clinical studies.
Keywords: post-antibiotic effects, PAEs, ketolides, streptococci,
staphylococci
Telithromycin post-antibiotic and post-antibiotic
sub-MIC effects for
10 Gram-positive cocci
2 Department of Pathology, Hershey Medical Center,
Hershey, PA, USA
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