a GR Micro Ltd, 79 William Road, London NW1 3ER; b Hoechst Marion Roussel, Broadwater Park, Denham, Uxbridge UB9 5HP; c Department of Clinical Microbiology, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
Sir,
We read with interest the recent leading article by Legg & Bint1 but cannot agree with all of the authors' conclusions. During the 19971998 winter season, an antimicrobial susceptibility surveillance study of community-acquired lower respiratory tract isolates of Streptococcus pneumoniae was conducted. The isolates were collected from 27 centres in the United Kingdom and Republic of Ireland. All isolates were sent to a central testing laboratory (GR Micro Ltd, London, UK) where their identity was confirmed using a combination of Gram's stain morphology, lack of catalase activity, susceptibility to ethylhydrocupreine and solubility in bile salts. MICs of a range of antimicrobials were determined using the NCCLS broth microdilution method with interpretation of the data undertaken for all compounds, except ciprofloxacin, using NCCLS breakpoint MIC.2,3 Interpretation breakpoints for use when testing the activity of ciprofloxacin against S. pneumoniae are not provided by the NCCLS. Therefore, those published for non-fastidious species (S 1, I = 2, R
4 mg/L), which correspond to those suggested by the BSAC, were used.4 The results, and their interpretation, are presented in the Table
. Penicillin resistance amongst isolates of S. pneumoniae is following a different pattern of evolution in the geographically separated areas of Great Britain and Ireland. During the study period, 90.9% of 663 combined isolates of S. pneumoniae collected from 21 centres in Great Britain were fully susceptible to penicillin, 3.5% exhibited low-level resistance (MIC 0.121 mg/L) and 5.6% high-level resistance (MIC
2 mg/L). In the same period, only 72.1% of 154 combined isolates collected from six centres in Ireland were fully susceptible to penicillin, with 4.5% exhibiting low-level resistance and 23.4% high-level resistance. Whatever the source, more of the isolates were classified as susceptible to amoxycillin/ clavulanate than to penicillin as a result of the higher breakpoints for amoxycillin (± clavulanate), which reflect the greater activity of the compound against strains of S. pneumoniae exhibiting low-level penicillin resistance (Table
).5 Whatever the geographical location, susceptibility to cefotaxime was similar to or better than that to amoxycillinclavulanate. Furthermore, a large proportion of the isolates of S. pneumoniae exhibiting high-level resistance to penicillin were interpreted as being of intermediate susceptibility (MIC 1 mg/L) to cefotaxime with the possibility of a clinical response to higher dosage of this parenteral cephalosporin. Overall, resistance to the macrolides (clarithromycin MIC
1 mg/L) was seen in 10.7% of isolates from Great Britain and 7.1% of those from Ireland. With regard to the fluoroquinolones, 64% of isolates from Great Britain and 63.6% from Ireland were susceptible (MIC
1 mg/L) to ciprofloxacin whereas 99.8% and 100%, respectively, were susceptible to levofloxacin (MIC
2 mg/L) (Table
). However, MICs of both ciprofloxacin and levofloxacin showed an essentially unimodal distribution for all isolates of S. pneumoniae, with mode values of 1 mg/L for both compounds. Only six isolates (0.7%) had ciprofloxacin MICs and two isolates (0.2%) had ofloxacin MICs of
8 mg/L. Legg & Bint1 draw attention to the fact that levofloxacin has shown efficacy in treating a variety of respiratory tract infections, which has been confirmed in a number of published clinical studies.6 Our study shows that despite the selective pressure brought about by the use of ciprofloxacin and ofloxacin for the treatment of respiratory tract and other infections during the past decade, there is no evidence of widespread evolution of quinolone resistance amongst isolates of S. pneumoniae. Therefore, we cannot agree with the conclusion drawn by Legg & Bint1 either of the likelihood of the short- to medium-term evolution of resistance as a result of the acquisition of sequential mutational events, or of the wisdom of reserving the fluoroquinolones, with improved activity against S. pneumoniae, for use in the empirical therapy of lower respiratory tract infections caused by isolates of the organism already exhibiting resistance to penicillin or other antimicrobials. Far better, in our opinion, that these new compounds be used generally for the treatment of lower respiratory tract infection, so as to increase the diversity of bacterial targets attacked and thus to reduce any pressure for the selection and maintenance of multiply-resistant isolates.
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Acknowledgments
We wish to express our gratitude to all those microbiologists, and their staff, who collaborated in this study. The study was funded by Hoechst Marion Roussel, Denham, UK.
Notes
J Antimicrob Chemother 2000; 45: 710711
* Corresponding author. Tel: +44-171-388-7320; Fax: +44-171-388-7324; E-mail: d.felmingham{at}grmicro.co.uk
References
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Legg, J. M. & Bint, A. J. (1999). Will pneumococci put quinolones in their place? Journal of Antimicrobial Chemotherapy 44, 4257.
2 . NCCLS. (1997). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow AerobicallyFourth Edition; Approved Standard. NCCLS Document M7-A4. NCCLS, Wayne, USA.
3 . NCCLS. (1998). Performance Standards for Antimicrobial Susceptibility Testing; Eighth Informational Supplement. NCCLS document M100-S8. NCCLS, Wayne, USA.
4 . Report of the Working Party on Antibiotic Sensitivity Testing of the British Society for Antimicrobial Chemotherapy. (1991). A guide to sensitivity testing. Journal of Antimicrobial Chemotherapy 27, Suppl. D, 150.[ISI][Medline]
5
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Butler, D. L., Gagnon, R. C., Miller, L. A., Poupard, J. A., Felmingham, D. & Grüneberg, R. N. (1999). Difference between the activity of penicillin, amoxycillin and co-amoxyclav against 5,252 Streptococcus pneumoniae isolates tested in the Alexander Project 19921996. Journal of Antimicrobial Chemotherapy 43, 77782.
6 . Zhanel, G. G., Walkty, A., Vercaigne, L., Karlowsky, J. A., Embil, J., Gin, A. S. et al. (1999). The new fluoroquinolones: a critical review. Canadian Journal of Infectious Disease 10, 20738.