Activity of gemifloxacin against invasive and multi-resistant Streptococcus pneumoniae isolates collected in the UK

A. P. Johnson1,*, M. Warner1, J. S. Nguyen-Van-Tam2,§ and D. M. Livermore1

1 Antibiotic Resistance Monitoring and Reference Laboratory, Central Public Health Laboratory, Colindale, London NW9 5HT; 2 SmithKline Beecham Pharmaceuticals plc (now part of GlaxoSmithKline plc), Welwyn Garden City AL7 3AY, UK

Keywords: gemifloxacin, Streptococcus pneumoniae

Sir,

Although anti-pneumococcal antibiotics have been available for 60 years, Streptococcus pneumoniae remains an important cause of morbidity and mortality, causing pneumonia, bacteraemia and meningitis, as well as less severe infections such as sinusitis and otitis media. The therapy of pneumococcal infections is often problematic, as strains resistant to first- and second-line agents are increasingly prevalent worldwide. For this reason there is an ongoing need for new agents, particularly those suitable for oral use. One increasingly favoured option is provided by new fluoroquinolones, many of which have improved anti-pneumococcal activity compared with ciprofloxacin.

This study was undertaken to assess the activity of the novel fluoroquinolone gemifloxacin against clinical isolates of S. pneumoniae obtained in the UK, and investigated 1082 isolates. These comprised 881 consecutive isolates received during the first 3 months of 2001 as part of a long term, ongoing programme that seeks all pneumococci from blood, CSF and other normally sterile sites, and 201 consecutive isolates submitted to the Reference Laboratory during the same time period, primarily for confirmation of resistance to first-line agents.

The surveillance and referred isolates were subjected to MIC determination with penicillin, cefotaxime, erythromycin, tetracycline, chloramphenicol, rifampicin, vancomycin, teicoplanin, ciprofloxacin, moxifloxacin and gemifloxacin. MICs were determined on Diagnostic Sensitivity Test agar (Oxoid, Basingstoke, UK) containing 5% lysed horse blood (TCS Microbiology, Buckingham, UK). The inocula comprised 104–105 cfu/spot, delivered with a multipoint inoculator. Incubation was for 18 h at 37°C in air and susceptibility was categorized using British Society for Antimicrobial Chemotherapy (BSAC) criteria.1

Resistance rates to established agents were low among the unselected invasive isolates, being as follows: penicillin 5.1% (3.4% intermediate, 1.7% fully resistant), cefotaxime 2.6%, erythromycin 14.4%, tetracycline 5.8% and chloramphenicol 1.1%. These figures are consistent with results from other UK surveys2,3 and are in contrast to the higher resistance rates often seen for invasive isolates from many other parts of the world.4 Unsurprisingly, higher resistance rates were seen among referred isolates, which comprised a biased sample, being representative of those pneumococci that UK laboratories perceive as warranting Reference Laboratory investigation. The proportions resistant to penicillin, cefotaxime, erythromycin, tetracycline and chloramphenicol were 87.1% (42.3% intermediate, 44.8% fully resistant), 12.4%, 48.8%, 40.8% and 21.4%, respectively. Resistance to rifampicin or glycopeptides was not seen in either the surveillance or referred isolates.

Although the referred isolates were more resistant than surveillance isolates to most agents, this behaviour did not extend to the fluoroquinolones. MICs of gemifloxacin ranged from 0.03 to 0.25 mg/L for the surveillance isolates and, with one exception, ranged from 0.03 to 0.125 mg/L for the referred isolates. The modal MICs were 0.06 mg/L for both groups. Using the gemifloxacin breakpoint of 0.25 mg/L recommended by the BSAC,1 99.9% of the isolates were susceptible. Moxifloxacin also had identical modal MICs (0.25 mg/L) for both the surveillance and referred isolates, with most MICs ranging between 0.125 and 1 mg/L for each group (Figure 1). Using the moxifloxacin breakpoint of 1 mg/L recommended by the BSAC, 99.8% of the isolates were susceptible. One exceptional referred isolate required gemifloxacin, moxifloxacin and ciprofloxacin MICs of 1, 8 and >8 mg/L, respectively.



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Figure 1. Distribution of quinolone MICs for surveillance and referred isolates of S. pneumoniae.

 
These data indicate that the novel fluoroquinolones gemifloxacin and moxifloxacin had excellent activity against pneumococci isolated in the UK during the first 3 months of 2001. Although the prevalence of quinolone resistance in pneumococci was low in the present series, trends towards increasing resistance have recently been noted in several other countries,5,6 suggesting the need for cautious use of these drugs. In this context, it seems preferable to use those fluoroquinolones with the most potent anti-pneumococcal activity, as these are the least likely to select for first step resistance mutants that are primed to achieve full resistance via further mutation.

Acknowledgements

We thank SmithKline Beecham Pharmaceuticals (now part of GlaxoSmithKline) for financial support.

Footnotes

* Corresponding author. Tel: +44-208-200-4400, ext. 4237; Fax: +44-208-358-3292; E-mail: ajohnson{at}phls.org.uk Back

§ Present address. Aventis Pasteur MSD Ltd, Maidenhead, Berks SL6 1QP, UK. Back

References

1 . Andrews, J. M. (2001). BSAC standardized disc susceptibility testing method. Journal of Antimicrobial Chemotherapy 48, Suppl. S1, S43–57.[CrossRef]

2 . Reacher, M. H., Shah, A., Livermore, D. M., Wale, C. J., Graham, C., Johnson, A. P. et al. (1999). Bacteraemia and antibiotic resistance of its pathogens reported in England and Wales between 1990 and 1998: trend analysis. British Medical Journal 320, 213–6.[Abstract/Free Full Text]

3 . Henwood, C. J., Livermore, D. M., Johnson, A. P., James, D., Warner, M., Gardiner A. et al. (2000). Susceptibility of Gram-positive cocci from 25 UK hospitals to antimicrobial agents including linezolid. Journal of Antimicrobial Chemotherapy 46, 931–40.[Abstract/Free Full Text]

4 . Hoban, D. J., Doern, G. V., Fluit, A. C., Roussel-Delvallez, M. & Jones, R. N. (2001). Worldwide prevalence of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the SENTRY Antimicrobial Surveillance Program, 1997–1999. Clinical Infectious Diseases 32, Suppl. 2, S81–93.[CrossRef][ISI][Medline]

5 . Chen, D. K., McGreer, A., De Azavedo, J. C. & Low, D. E. (1999). Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. New England Journal of Medicine 341, 223–9.[CrossRef]

6 . Ho, P.-K., Que, T.-L., Tsang, D. N.-C., Ng, T.-K., Chow, K.-H. & Seto, W.-H. (1999). Emergence of fluoroquinolone resistance among multiply resistant strains of Streptococcus pneumoniae in Hong Kong. Antimicrobial Agents and Chemotherapy 43, 1310–3.[Abstract/Free Full Text]





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