Emergence of resistance to rifampin and rifalazil in Chlamydophila pneumoniae and Chlamydia trachomatis.
Although rifamycins have excellent activity against Chlamydophila pneumoniae and Chlamydia trachomatis in vitro, concerns about the possible development of resistance during therapy have discouraged their use for treatment of chlamydial infections. Rifalazil, a new semisynthetic rifamycin with a long half-life, is the most active antimicrobial against C. pneumoniae and C. trachomatis in vitro, indicating its potential for treatment of acute and chronic C. pneumoniae and C. trachomatis infections. We investigated the effect of serial passage of two C. pneumoniae isolates and two serotypes of C. trachomatis in subinhibitory concentrations of rifalazil and rifampin on the development of phenotypic and genotypic resistance. C. trachomatis developed resistance to both antimicrobials within six passages, with higher level resistance to rifampin (128 to 256 microg/ml) and lower level resistance to rifalazil (0.5 to 1 microg/ml). C. pneumoniae TW-183 developed only low-level resistance to rifampin (0.25 microg/ml) and rifalazil (0.016 microg/ml) after 12 passages. C. pneumoniae CWL-029 failed to develop resistance to either drug. Two unique mutations emerged in the rpoB gene of rifampin (L456I) and rifalazil (D461E)-resistant C. pneumoniae TW-183. A single mutation (H471Y) was detected in both rifampin- and rifalazil-resistant C. trachomatis UW-3/Cx/D, and a unique mutation (V136F) was found in rifalazil-resistant BU-434/L(2). No mutations were detected in the entire rpoB gene of rifampin-resistant BU-434/L(2). This is the first description of antibiotic resistance-associated mutations in C. pneumoniae and of rifampin resistance in C. trachomatis not associated with mutations in the rpoB gene.
Kutlin
Andrei
A
Department of Pediatrics, SUNY Downstate Medical Center, 450 Clarkson Avenue, Box 49, Brooklyn, NY 11203, USA. kutlin@downstate.edu
Kohlhoff
Stephan
S
Roblin
Patricia
P
Hammerschlag
Margaret R
MR
Riska
Paul
P
D001483:Base Sequence; D002692:Chlamydia trachomatis / Q000187:drug effects* / Q000235:genetics; D016993:Chlamydophila pneumoniae / Q000187:drug effects* / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D024881:Drug Resistance, Bacterial; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D012293:Rifampin / Q000494:pharmacology*; D012294:Rifamycins / Q000494:pharmacology*
D012294:Rifamycins; C068980:KRM 1648; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit; D012293:Rifampin
Antimicrob Agents Chemother. 2001 Jul;45(7):1972-6
11408210
J Clin Microbiol. 1999 Sep;37(9):2913-9
10449475
Antimicrob Agents Chemother. 2001 Nov;45(11):3001-8
11600348
Chest. 2002 Jun;121(6):1782-8
12065339
Expert Opin Investig Drugs. 2003 Feb;12(2):255-71
12556219
Antimicrob Agents Chemother. 2003 Mar;47(3):1135-6
12604555
Antimicrob Agents Chemother. 2003 Jul;47(7):2316-8
12821487
Cell Microbiol. 2004 Feb;6(2):117-27
14706098
Andrologia. 2004 Feb;36(1):1-23
14871260
J Am Geriatr Soc. 2004 Mar;52(3):381-7
14962152
Antimicrob Agents Chemother. 2004 Apr;48(4):1347-9
15047540
Curr Opin Infect Dis. 2004 Feb;17(1):49-52
15090891
Rev Infect Dis. 1983 Jul-Aug;5 Suppl 3:S556-61
6635445
Rev Infect Dis. 1983 Jul-Aug;5 Suppl 3:S562-4
6635446
Mol Gen Genet. 1984;196(1):173-4
6384726
J Mol Biol. 1988 Jul 5;202(1):45-58
3050121
Antimicrob Agents Chemother. 1989 Aug;33(8):1393-4
2552911
Antimicrob Agents Chemother. 1994 Jun;38(6):1256-61
8092823
Antimicrob Agents Chemother. 1995 Apr;39(4):1007-9
7785970
J Antimicrob Chemother. 1996 Feb;37(2):357-9
8707747
Antimicrob Agents Chemother. 1996 Mar;40(3):646-51
8851587
Antimicrob Agents Chemother. 1996 Dec;40(12):2749-55
9124834
J Med Microbiol. 1998 Mar;47(3):197-200
9511824
Nature. 1998 Jun 11;393(6685):537-44
9634230
Antimicrob Agents Chemother. 1998 Oct;42(10):2590-4
9756760
J Antimicrob Chemother. 1998 Nov;42(5):621-8
9848446
Antimicrob Agents Chemother. 1999 Apr;43(4):960-2
10103210
Antimicrob Agents Chemother. 1999 Jul;43(7):1808-10
10390251
Antimicrob Agents Chemother. 2001 Aug;45(8):2198-203
11451674