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Antimicrobial Agents and Chemotherapy, November 2001, p. 3001-3008, Vol. 45, No. 11
Department of Internal Medicine, Division of
Rheumatology, Medical School Hannover, Hannover, Germany
Received 18 April 2001/Returned for modification 21 June
2001/Accepted 9 August 2001
An in vitro cell culture model was used to investigate the
long-term effects of azithromycin, rifampin, and the combination of
azithromycin and rifampin on Chlamydia trachomatis
infection. Although standard in vitro susceptibility testing indicated
efficient inhibition by azithromycin, prolonged treatment did not
reveal a clear elimination of chlamydia from host cells. Chlamydia were temporarily arrested in a persistent state, characterized by
culture-negative, but viable, metabolically active chlamydia, as
demonstrated by the presence of short-lived rRNA transcripts.
Additionally, azithromycin induced generation of aberrant inclusions
and an altered steady-state level of chlamydial antigens, with the
predominance of Hsp60 protein compared to the level of the major
outer membrane protein. Treatment with azithromycin finally resulted in
suppression of rRNA synthesis. Chlamydial lipopolysaccharide and
processed, functional rRNA were detectable throughout the entire
incubation period. These in vitro data show a good correlation to those
from some recent clinical investigations that have reported on the
persistence of chlamydia, despite appropriate antibiotic treatment with
azithromycin. Rifampin was highly active by in vitro susceptibility
testing, but prolonged exposure to rifampin alone for up to 20 days
resulted in the emergence of resistance. No development of resistance
to rifampin was observed when chlamydia-infected cells were incubated
with a combination of azithromycin and rifampin. This combination was
shown to be more efficient than azithromycin alone, in that suppression
of rRNA synthesis occurred earlier. Thus, such a combination may prove
more useful than azithromycin alone.
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.11.3001-3008.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Effects of Azithromycin and Rifampin on
Chlamydia trachomatis Infection In Vitro

*
Corresponding author. Mailing address: Department of
Rheumatology, Medical School Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Phone: 49/511-5322319. Fax: 49/511-5325841. E-mail:
Koehler.Lars{at}mh-hannover.de.
Present address: Department of Immunology and Microbiology, Wayne
State University, School of Medicine, Detroit, MI 48201.
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