The in vitro activity of a new fluoroquinolone, ABT-492, against recent clinical isolates of Chlamydia pneumoniae

Margaret R. Hammerschlag* and Patricia M. Roblin

Chlamydia Research Laboratory, Division of Infectious Diseases, Department of Pediatrics, State University of New York, Downstate Medical Center, Brooklyn, NY 11203-2098, USA

Keywords: fluoroquinolones , C. pneumoniae , community-acquired pneumonia

Sir,

As part of our research into the diagnosis and treatment of infection due to Chlamydia spp., we have had the opportunity to test a number of new compounds against these organisms. Harnett et al.1 recently reported a comparative study of the in vitro activity of a new fluoroquinolone, ABT-492, against a wide range of bacteria, including three strains of Chlamydia trachomatis and one isolate of Chlamydia pneumoniae. We recently tested ABT-492 against 13 recent clinical isolates of C. pneumonia from patients with community-acquired pneumonia enrolled in a multicentre treatment study.

Isolates and comparator antibiotics used in the study are presented in Table 1. Antibiotics were provided by the manufacturers. Antibiotic susceptibility testing was performed in cycloheximide-treated HEp-2 cells grown in 96-well microtitre plates, as previously described.2 MICs and MBCs are summarized in Table 1. The MIC90 and MBC90 of ABT-492 were 0.125 mg/L (range 0.06–0.125 mg/L) compared with 0.125 mg/L for azithromycin and 0.5 mg/L for levofloxacin. The activity of ABT-492 against C. pneumoniae was similar to those we have previously reported for gatifloxacin, moxifloxacin and gemifloxacin.3 However, these results were four-fold higher than the MIC of 0.03 mg/L Harnett et al.1 reported for the one isolate of C. pneumoniae (TW-183) tested in their study. Harnett et al. used McCoy cells, which are 10–100-fold less susceptible to C. pneumoniae than the HEp-2 cells used in the present study, which may lead to lower endpoints.


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Table 1. Activities of ABT-492, levofloxacin and azithromycin against 13 isolates of C. pneumoniae

 
The discrepancy of MICs between these studies illustrates the problems of in vitro susceptibility testing of Chlamydia spp. in general and C. pneumoniae specifically. The methods are not standardized and the number of isolates available for testing are limited. Wide isolate-to-isolate variation in MICs has been seen with some antibiotics, most notably telithromycin.4 Data on the actual microbiological efficacy of quinolones for eradication of C. pneumoniae from patients with respiratory infection are limited; most treatment studies that have been published in the literature have used serology alone. The limited data that are available suggest that in vitro activity does not necessarily predict in vivo efficacy. Indeed, there are no data that demonstrate that an antibiotic with an MIC of 0.1 mg/L is more effective in eradication of C. pneumoniae than one with an MIC of 1 mg/L.

Footnotes

* Corresponding author. Tel: +1-718-270-3097; Fax: +1-718-270-1985; Email: mhammerschlag{at}pol.net

References

1 . Harnett, S. J., Fraise, A. P., Andrews, J. M. et al. (2004). Comparative study of the in vitro activity of a new fluoroquinolone, ABT-492. Journal of Antimicrobial Chemotherapy 53, 783–92.[Abstract/Free Full Text]

2 . Hammerschlag, M. R., Reznik, T., Roblin, P. M. et al. (2003). Microbiological efficacy of ABT-773 (cethromycin) for treatment of community acquired pneumonia due to Chlamydia pneumoniae. Journal of Antimicrobial Chemotherapy 51, 1025–8.[Abstract/Free Full Text]

3 . Hammerschlag, M. R. (2000). Activity of gemifloxacin and other new quinolones against Chlamydia pneumoniae: a review. Journal of Antimicrobial Chemotherapy 45, Suppl. S1, 35–9.[Abstract/Free Full Text]

4 . Roblin, P. M. & Hammerschlag, M. R. (1998). In vitro activity of a new ketolide antibiotic, HMR 3647, against Chlamydia pneumoniae. Antimicrobial Agents and Chemotherapy 42, 1515–6.[Abstract/Free Full Text]





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