Reply

Joseph M. Blondeau*

Department of Clinical Microbiology, Saskatoon and District Health and St Paul's Hospital, Saskatoon, Saskatchewan, Canada

Sir,

Recently Legg & Bint1 asked, "Whether the quinolones would be put in their place by the pneumococcus?" Since this article, two new fluoroquinolones have been released in the USA, with another under review. We examined >1000 recent clinical isolates of Streptococcus pneumoniae for their susceptibility to two of these fluoroquinolones, moxifloxacin and gatifloxacin.

Using the microbroth dilution method,2 we tested 1037 strains isolated from sputum, CSF and blood. The TableGo shows the MIC90s of the two drugs: gatifloxacin 0.5 mg/L and moxifloxacin 0.25 mg/L. These data corroborate those of studies in which the agents were tested separately against S. pneumoniae.


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Table. MIC50, MIC90 and range of gatifloxacin and moxifloxacin for Streptococcus pneumoniae
 
Furthermore, other data indicate that moxifloxacin is at least 2- to 4-fold more potent than other fluoroquinolones in vitro when assessed by the mutation prevention concentration (MPC) method3 and pharmacodynamic data suggest that moxifloxacin should not only be clinically effective but also maintain low levels of resistance, unlike levofloxacin which from in vitro, MPC and PK/PD analyses is predicted to compromise long-term susceptibility of S. pneumoniae if used at once-daily dosing. Quinolones with borderline (near breakpoint) activity against the pneumococcus clearly need to be used at higher doses (where possible) and/or with more frequent dosing in order to minimize the selection of resistance. We need to insist on this strategy now.

Clearly, MICs tell us only so much; future fluoroquinolones may be more active in the test tube but their tissue/serum levels may not permit adequate therapeutic indices over the entire dosing period in order to minimize the selection of resistance.

Legg & Bint were right to ask the question, but the answer as always is ‘it depends’.

Notes

J Antimicrob Chemother 2000; 46: 323

* Correspondence address. Royal University Hospital, 103 Hospital Drive, Saskatoon, SK, Canada SN7 4PI. Tel: +1-306-655-6943; Fax: +1-306-655-6947; E-mail: blondeauj{at}sdh.sk.ca Back

References

1 . Legg, J. M. & Bint, A. J. (1999). Will pneumococci put quinolones in their place? Journal of Antimicrobial Chemotherapy 44, 425–7.[Free Full Text]

2 . National Committee for Clinical Laboratory Standards. (1999). Performance Standards for Antimicrobial Susceptibility Testing: M7-S9. NCCLS, Vilanova, PA.

3 . Blondeau, J. M., Borsos, S. & Drlica, K. (1999). Mutation prevention concentration of moxifloxacin and levofloxacin against clinical isolates of S. pneumoniae and S. aureus. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, California, September 26–29, 1999. Abstract 032.E. American Society for Microbiology, Washington, DC.