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Antimicrobial Agents and Chemotherapy, January 2001, p. 23-29, Vol. 45, No. 1
Antibiotic Research Unit, Department of
Infectious Diseases and Clinical Microbiology, University Hospital,
Uppsala, Sweden
Received 28 February 2000/Returned for modification 14 May
2000/Accepted 3 September 2000
Telithromycin (HMR 3647) is a new ketolide that belongs to a new
class of semisynthetic 14-membered-ring macrolides which have expanded
activity against multidrug-resistant gram-positive bacteria. The aim of
the present study was to investigate different basic pharmacodynamic
properties of this new compound. The following studies of telithromycin
were performed: (i) studies of the rate and extent of killing of
respiratory tract pathogens with different susceptibilities to
erythromycin and penicillin exposed to a fixed concentration that
corresponds to a dose of 800 mg in humans, (ii) studies of the rate and
extent of killing of telithromycin at five different concentrations,
(iii) studies of the rate and extent of killing of the same pathogens
at three different inocula, (iv) studies of the postantibiotic effect
and the postantibiotic sub-MIC effect of telithromycin, and (v)
determination of the rate and extent of killing of telithromycin in an
in vitro kinetic model. In conclusion, telithromycin exerted an
extremely fast killing of all strains of Streptococcus
pneumoniae both with static concentrations and in the in vitro
kinetic model. A slower killing of the strains of Streptococcus
pyogenes was noted, with regrowth in the kinetic model of a
macrolide-lincosamide-streptogramin B-inducible strain. The strains of
Haemophilus influenzae were not killed at all at a
concentration of 0.6 mg/liter due to high MICs. A time-dependent
killing was seen for all strains. No inoculum effect was seen for the
strains of S. pneumoniae, with a 99.9% reduction in the
numbers of CFU for all inocula at both 8 h and 24 h. The
killing of the strains of S. pyogenes was reduced by 1 log10 CFU at 8 h and 2 to 3 log10 CFU at
24 h when the two lower inocula were used but not at all at 8 and
24 h when the highest inoculum was used. For both of the H. influenzae strains there was an inoculum effect, with 1 to 2 log10 CFU less killing for the inoculum of 108
CFU/ml in comparison to that for the inoculum of 106
CFU/ml. Overall, telithromycin exhibited long postantibiotic effects
and postantibiotic sub-MIC effects for all strains investigated.
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.1.23-29.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Pharmacodynamics of Telithromycin In Vitro against
Respiratory Tract Pathogens
*
Corresponding author. Mailing address: Department of
Infectious Diseases, University Hospital, MAS, S-20502 Malmö,
Sweden. Phone: (46)-40-331806. Fax: (46)-40-336279. E-mail:
inga.odenholt{at}inf.mas.lu.se.
Antimicrobial Agents and Chemotherapy, January 2001, p. 23-29, Vol. 45, No. 1
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.1.23-29.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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