BSAC Respiratory Resistance Surveillance Programme (2002–2003): comparative susceptibility of Streptococcus pneumoniae, cultured from patients in Great Britain and Ireland with community-acquired lower respiratory tract infection, to gemifloxacin

David Felmingham1,*, Jemma Shackcloth1 and Glenn Tillotson2

1 GR Micro Ltd, London, UK; 2 Oscient Pharmaceuticals, Waltham, MA, USA

Keywords: S. pneumoniae , RTIs , antibacterials , resistance

Sir,

Streptococcus pneumoniae is an important pathogen of the respiratory tract where it may be responsible for a wide range of infections including community-acquired pneumonia, acute exacerbations of chronic bronchitis and obstructive airways disease, sinusitis and otitis media.1

Therapeutic choice for infections which are likely to include S. pneumoniae among the causative bacteria is increasingly complicated by resistance to a range of otherwise suitable antimicrobials with the prevalence of resistance reaching alarming proportions in the Far East region, the USA and some countries within Europe.2 Global, national and local surveillance programmes are essential aids in defining rates and the evolution of antimicrobial resistance.3

The BSAC Respiratory Resistance Surveillance Programme began in 1999 and exists to provide long-term, large-scale antimicrobial susceptibility surveillance of the major pathogens causing community-acquired lower respiratory tract infections in Great Britain and Ireland, including S. pneumoniae.3

Gemifloxacin is a novel, fluorinated, naphthyridone antibacterial characterized by excellent activity against Gram-negative species typical of most fluoroquinolones, whilst possessing enhanced potency against Gram-positive bacterial pathogens, most notably S. pneumoniae, which exceeds that of other currently licensed members of this class of antimicrobials.4

During the 2002–2003 ‘cold season’, as part of the BSAC Resistance Surveillance Programme, the susceptibility of 772 isolates of S. pneumoniae to various antimicrobials, including gemifloxacin, was determined using BSAC procedures and interpretation of results.3 The results are presented in Table 1.


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Table 1. Comparative in vitro activity of gemifloxacin against 772 isolates of S. pneumoniae, cultured from patients in Great Britain and Ireland with community-acquired lower respiratory tract infection, examined in the BSAC Respiratory Resistance Surveillance Programme (2002–2003)

 
Non-susceptibility to penicillin (intermediate, MIC 0.12–1 mg/L, 8.3% + high-level resistance, MIC ≥2 mg/L, 0.3%) was found in a total of 8.6% of the isolates of S. pneumoniae. Erythromycin resistance was found in 10% of the isolates of S. pneumoniae with 4.7% resistant to clindamycin suggesting an approximately even distribution between strains exhibiting macrolide, lincosamide, streptogramin (MLSB) resistance mediated through the erm(B)-encoded methylase and those characterized by inducible mef(A)-mediated efflux. A small percentage (6.2%) of the isolates were resistant to tetracycline whilst the great majority (99.9%) were resistant to trimethoprim. Using BSAC breakpoints,3 96.2% of the 772 isolates of S. pneumoniae were of intermediate susceptibility to ciprofloxacin (MIC ≤2 mg/L) and 3.8% were resistant (MIC >2 mg/L). In contrast, 99.5% of the isolates were susceptible to moxifloxacin (MIC ≤1 mg/L) and to gemifloxacin (MIC ≤0.25 mg/L) reflecting the greater potency of these two fluoroquinolones with gemifloxacin being 4- to 8-fold more active than moxifloxacin.

Clinical trials of gemifloxacin have demonstrated good efficacy, and a safety and tolerance profile similar to that of comparator compounds including fluoroquinolones, ß-lactams and macrolides.5,6 On this evidence, gemifloxacin was approved by the United States Food and Drug Administration (FDA) in 2003 for the treatment of mild-to-moderate community-acquired pneumonia and acute exacerbation of chronic bronchitis including those infections caused by multidrug-resistant strains of S. pneumoniae (data accessed on http://www.fda.gov/cder/foi/appletter/2003/21158se1-001ltr.pdf).

The data presented herein confirm the enhanced activity of gemifloxacin against strains of S. pneumoniae collected from throughout Great Britain and Ireland regardless of their resistance to other, unrelated antimicrobials. Thus, gemifloxacin may be a useful additional therapeutic option for the treatment of respiratory tract infections, particularly those in which S. pneumoniae is implicated and especially in areas with a high prevalence of antimicrobial resistance among isolates of this important pathogen.

Footnotes

* Corresponding author. Tel: +44-207-3887320; Fax: +44-207-3887324; Email: d.felmingham{at}grmicro.co.uk

References

1 . Musher, D. M. (2000). Streptococcus pneumoniae. In Principles of Infectious Disease (Mandell, G. L., Bennett, J. E. & Dolin, R., Eds), pp. 2128–44. Churchill Livingstone, Edinburgh, UK.

2 . Felmingham, D., Reinert, R. R., Hirakata, Y. et al. (2002). Increasing prevalence of resistance among isolates of Streptococcus pneumoniae from the PROTEKT surveillance study, and comparative in vitro activity of the ketolide, telithromycin. Journal of Antimicrobial Chemotherapy 50, Suppl. S1, 25–37.[Abstract/Free Full Text]

3 . Reynolds, R., Shackcloth, J., Felmingham, D. et al. (2003). Antimicrobial susceptibility of lower respiratory tract pathogens in Great Britain and Ireland 1999–2001 related to demographic and geographical factors: the BSAC Respiratory Resistance Surveillance Programme. Journal of Antimicrobial Chemotherapy 52, 931–43.[Abstract/Free Full Text]

4 . King, A., May, J., French, G. et al. (2000). Comparative in vitro activity of gemifloxacin. Journal of Antimicrobial Chemotherapy 45, Suppl. S1, 1–12.[Abstract/Free Full Text]

5 . Ball, P., File, T. M., Twynholm, M. et al. (2001). Efficacy and safety of gemifloxacin 320 mg once-daily for 7 days in the treatment of adult lower respiratory tract infections. International Journal of Antimicrobial Agents 18, 19–27.[CrossRef][ISI][Medline]

6 . Ball, P., Mandell, L., Paton, G. et al. (2004). A new respiratory fluoroquinolone, oral gemifloxacin: a safety profile in context. International Journal of Antimicrobial Agents 23, 421–9.[CrossRef][ISI][Medline]





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