Bactericidal activity of levofloxacin against Mycoplasma pneumoniae

Lynn B. Duffy1, Donna M. Crabb1, Xue Bing1 and Ken B. Waites1,2,*

Departments of 1 Microbiology and 2 Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

Keywords: M. pneumoniae, levofloxacin, fluoroquinolones, bactericidal activity, respiratory tract infections

Sir,

Mycoplasma pneumoniae infects persons of all age groups and is responsible for as much as 25–50% of community-acquired pneumonias.1 It is also a common cause of tracheobronchitis. Fatal pneumonias and disseminated infections involving the central nervous system, joints and other organs sometimes occur.1 Disease may be especially severe and prolonged in persons who are immunosuppressed.1 Cost and limited availability of diagnostic tests mandate that treatment for M. pneumoniae infections must be given empirically in most settings. Macrolides and tetracyclines possess bacteriostatic activity, but fluoroquinolones represent the only drugs likely to be bactericidal against this organism.2

Levofloxacin has been shown to be active in vitro against M. pneumoniae.26 This study was undertaken to evaluate the in vitro activity of levofloxacin against a large number of recent clinical isolates of M. pneumoniae recovered from patients with proven respiratory tract disease and to assess its bactericidal activities against a subgroup of these organisms by determining MBCs and carrying out time–kill assays.

One-hundred and two M. pneumoniae isolates were tested. These organisms were isolated from the respiratory tract of individuals with proven respiratory disease from six different countries between 1992 and 2000. Several of the isolates were obtained from outbreaks in the United States within the past 5 years. Some of these organisms have been evaluated in vitro against various fluoroquinolones in earlier studies.2,4 A microbroth dilution method was used to determine MICs. A subgroup of 12 randomly chosen isolates was tested to determine MBCs of levofloxacin directly from microtitre plates used to determine MICs. Two of these isolates were chosen for time–kill assays. Methods for each of these assays have been described in detail elsewhere.2

All 102 M. pneumoniae isolates were inhibited by levofloxacin within clinically achievable concentrations ranging from 0.063 to 2 mg/L with MIC50 = 0.5 mg/L and MIC90 = 2.0 mg/L. MBCs for 10 of 12 (83%) isolates were 2–4 times the MIC, indicating bactericidal effect.

Plots of time–kill assays for two isolates with levofloxacin MICs = 0.5 mg/L and MBCs = 2 mg/L (4x MIC) are shown in Figure 1. Bactericidal effect for time–kill assays (99.9% killing) or reduction in inoculum by >=3 log10 dilutions occurred after 24 h at 8x MIC in one isolate and after 48 h in both isolates at concentrations >=2x MIC. No regrowth exceeding 102 cfu/mL was observed.



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Figure 1. Time–kill plots for two M. pneumoniae isolates (MICs = 0.5 mg/L) in which levofloxacin was tested at concentrations of 0.5 to 8 times the corresponding MICs.

 
This is the first report describing MICs, MBCs and time–kill assays to assess bactericidal activity of levofloxacin against M. pneumoniae in the largest collection of clinical isolates reported to date. In 10 out of 12 randomly selected isolates, a bactericidal effect was demonstrated, supporting the use of levofloxacin against M. pneumoniae infections, including serious infections in which killing the organism may be of importance.

Acknowledgements

This work was presented at the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, USA, September, 2002.

Footnotes

* Corresponding author. Tel: +1-205-934-0578; Fax: +1-205-975-4468; E-mail: waites{at}path.uab.edu Back

References

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2 . Waites, K. B., Crabb, D. M., Bing, X. et al. (2003). In vitro susceptibilities to and bactericidal activities of garenoxacin (BMS-284756) and other antimicrobial agents against human mycoplasmas and ureaplasmas. Antimicrobial Agents and Chemotherapy 47, 161–5.[Abstract/Free Full Text]

3 . Bébéar, C. M., Renaudin, H., Bryskier, A. et al. (2000). Comparative activities of telithromycin (HMR 3647), levofloxacin, and other antimicrobial agents against human mycoplasmas. Antimicrobial Agents and Chemotherapy 44, 1980–2.[Abstract/Free Full Text]

4 . Duffy, L. B., Crabb, D., Searcey, K. et al. (2000). Comparative potency of gemifloxacin, new quinolones, macrolides, tetracycline and clindamycin against Mycoplasma spp. Journal of Antimicrobial Chemotherapy 45, Suppl. S1, 29–33.[Abstract/Free Full Text]

5 . Hamamoto, K., Shimizu, T., Fujimoto, N. et al. (2001). In vitro activities of moxifloxacin and other fluoroquinolones against Mycoplasma pneumoniae. Antimicrobial Agents and Chemotherapy 45, 1908–10.[Abstract/Free Full Text]

6 . Kenny, G. E. & Cartwright, F. D. (2001). Susceptibilities of Mycoplasma hominis, M. pneumoniae, and Ureaplasma urealyticum to GAR-936, dalfopristin, dirithromycin, evernimicin, gatifloxacin, linezolid, moxifloxacin, quinupristin–dalfopristin, and telithromycin compared to their susceptibilities to reference macrolides, tetracyclines, and quinolones. Antimicrobial Agents and Chemotherapy 45, 2604–8.[Abstract/Free Full Text]