title: Respiratory pathogens: assessing resistance patterns in Europe and the potential role of grepafloxacin as treatment of patients with infections caused by these organisms.
abstract: Although most respiratory tract infections (RTI) are caused by viruses, various bacteria, particularly Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, are common causes of community-acquired pneumonia, acute exacerbations of chronic bronchitis, otitis media and sinusitis. Empirical antibiotic therapy of patients with RTI must take account of the increasing prevalence of resistance among the predominant pathogens. Europe-wide susceptibility surveillance studies have revealed that resistance to penicillin and macrolides is highly prevalent among isolates of S. pneumoniae from France and Spain. Uniquely, in Italy, macrolide resistance is highly prevalent while the prevalence of penicillin resistance is low. Resistance to other antibiotic classes, including chloramphenicol, doxycycline and, in particular, co-trimoxazole, is associated with penicillin resistance in pneumococci, but resistance to the fluoroquinolones is rare. beta-Lactamase production is the principal mechanism of resistance in isolates of H. influenzae and M. catarrhalis, with fluoroquinolone resistance being detected rarely in these pathogens. In 1998 a surveillance study involving 15 European countries determined the susceptibilities of many respiratory pathogens to a range of antimicrobials, including grepafloxacin. The MIC(90) of grepafloxacin for 1251 isolates of S. pneumoniae was 0.25 mg/L, the MICs for only five strains being >2 mg/L, and 99.4% of all of the isolates tested were inhibited by concentrations </=0.5 mg/L. The MIC(90)s of grepafloxacin for 587 isolates of H. influenzae and 323 of Haemophilus parainfluenzae were 0.015 and 0.06 mg/L, respectively, while that for 509 isolates of M. catarrhalis was 0.03 mg/L. The MIC(90)s for 1164 isolates of methicillin-susceptible Staphylococcus aureus and 435 isolates of Klebsiella pneumoniae were 0.12 and 0.25 mg/L, respectively. Other studies have shown grepafloxacin to be highly active against clinical isolates of Legionella pneumophila (MIC(90) 0.015 mg/L), Mycoplasma pneumoniae (MIC(90) 0.5 mg/L) and Chlamydia pneumoniae (MICs 0.06-0.12 mg/L). Current susceptibility data indicate that fluoroquinolone resistance rates among bacterial respiratory tract pathogens are low in European countries. The enhanced potency and activity of grepafloxacin against isolates of S. pneumoniae, including those exhibiting resistance to unrelated classes of antibiotics, together with its activity against other respiratory tract pathogens, suggest that this drug has considerable potential as empirical therapy of patients with a wide range of RTI.
authors.affiliation: GR Micro Ltd, 7-9 William Road, London NW1 3ER, UK. d.felmingham@grmicro.uk
authors.forename: D
authors.initials: D
authors.lastname: Felmingham
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D003625:Data Collection; D004352:Drug Resistance, Microbial; D005060:Europe / Q000453:epidemiology; D024841:Fluoroquinolones; D006801:Humans; D008826:Microbial Sensitivity Tests; D010879:Piperazines / Q000494:pharmacology*; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology*
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D010879:Piperazines; C075375:grepafloxacin