Activities of Ciprofloxacin and Sparfloxacin against

Abstract

Bacterial pneumonia remains an infection with substantial mortality, irrespective of whether the pneumonia is hospitalor community-acquired. Streptococcus pneumoniae is one of the pathogens in the wide range of bacteria causing nosocomial pneumonia, and it is still the leading organism implicated in community-acquired pneumonia. Because of borderline minimum inhibitory concentrations (MICs) against S. pneumoniae, fluoroquinolones such as ciprofloxacin were not regarded as drugs of choice in the treatment of lower respiratory tract infections, whereas sparfloxacin, for example, appears to be potentially useful because of its improved in vitro activity. On the other hand, clinical studies have proven that ciprofloxacin is clinically and bacteriologically highly effective in the treatment of communityacquired[1,2l and severe pneumonia in hospitalised patients,[3l with clinical success rates and eradication of S. pneumoniae ranging from 93 to 100%. It is tempting to speculate that the marked penetration of ciprofloxacin into the respiratory tract is one of the factors contributing to the clinical efficacy of this agent against S. pneumoniae. Irrespective of the route of administration and dose administered' ciprofloxacin concentrations in human lung tissue and bronchial mucosa exceed the corresponding serum concentrations, and thus the ciprofloxacin MICs against S. pneumoniae, by 3to 20-fold.[4-8l In particular, multiple doses of oral or IV ciprofloxacin resulted in mean maximal concentrations at the site of infection (i.e. human lung tissue) of approximately 20 mg/kg. Penetration of sparfloxacin into the bronchial mucosa is less marked, and sparfloxacin concentrations in bronchial mucosa exceed the corresponding serum concentrations by 3.0to 3.7-foldP,lOl However, sparfloxacin is more effectively taken up by macrophages than ciprofloxacin. Whether, compared with ciprofloxacin, the high intracellular sparfloxacin concentrations in phagocytic cells compensate for the lower tissue concentrations is a yet unanswered question. The aim of this study was to compare the in vitro bactericidal activities of sparfloxacin and ciprofloxacin by simulating the quinolone concentrations at the site of infection (the bronchial mucosa), either in the absence or presence of macrophages.