Sparfloxacin

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Abstract
Sparfloxacin is a fluoroquinolone antibacterial agent with activity against a broad range of Gram-negative and Gram-positive organisms including Streptococcus pneumoniae, one of the main pathogens in community-acquired pneumonia. In this infection, sparfloxacin has shown efficacy similar to that of amoxicillin, erythromycin, roxithromycin, amoxicillin/clavulanic acid and amoxicillin plus ofloxacin, producing clinical cure rates of 80 to 84% assessed by intention-to-treat analyses in European or multinational trials. US studies showed similar results for sparfloxacin to those for erythromycin and cefaclor. Sparfloxacin was also as effective as all other comparator drugs in patients with other lower respiratory tract infections, usually acute exacerbations of chronic obstructive pulmonary disease (COPD). The profile of adverse effects for sparfloxacin is generally similar to that of other quinolones: gastrointestinal discomfort and CNS effects are the most common in clinical trials. Sparfloxacin causes fewer gastrointestinal disturbances than agents such as amoxicillin and erythromycin and does not interact with theophylline, an important consideration when treating patients with respiratory disease. Its long elimination half-life permits once-daily dosage regimens. On the other hand, there are infrequent reports of prolonged QTc interval (3% increase) during sparfloxacin therapy. Photo sensitivity occurs more frequently than with the other fluoroquinolones (2% of patients in an ongoing postmarketing study and 7.9% of those in US trials), and requires ongoing surveillance. In summary, the good activity of sparfloxacin against S. pneumoniae and other respiratory pathogens supports its use in lower respiratory tract infections, particularly community-acquired pneumonia. Its profile of good efficacy, once-daily dosage, good gastrointestinal tolerability and lack of interaction with theophylline are advantageous, but clinicians and patients must be alert to the possibility of photosensitivity reactions. On this basis, sparfloxacin, when appropriately prescribed, can provide the clinician with a useful alternative treatment option for these common infections. Sparfloxacin, like other fluoroquinolones, prevents bacterial growth primarily by inhibiting the action of DNA gyrase. Resistance to fluoroquinolones is thought to be mediated mainly via structural changes to DNA gyrase. Resistance to sparfloxacin and cross-resistance to other fluoroquinolones has been observed in vitro and in clinical studies but as yet at a low frequency. As with other quinolones, sparfloxacin displays a postantibiotic effect in vitro and is bactericidal at concentrations similar to or twice that of the minimum inhibitory concentrations (MICs) for susceptible pathogens. Sparfloxacin is active against virtually all common respiratory pathogens. It shows good activity against Gram-positive organisms while retaining activity against Gram-negative bacteria. S. pneumoniae, including penicillin- and erythromycin-resistant strains, are susceptible to sparfloxacin, as are ciprofloxacin-sensitive Staphylococcus aureus. Ciprofloxacin- and methicillin-resistant S. aureus strains are generally not susceptible to sparfloxacin. Gram-negative respiratory pathogens (e.g. β-lactamase positive and negative Haemophilus influenzae and Moraxella catarrhalis) are susceptible to sparfloxacin, as are Enterobacteriaceae. The drug is very active against Mycoplasma pneumoniae. Chlamydia pneumoniae is also inhibited by low concentrations of sparfloxacin, which is more active than ofloxacin against this organism and against M. pneumoniae. MIC90S are 4-fold lower for sparfloxacin than for ciprofloxacin against Mycobacterium tuberculosis, including multidrug-resistant strains. Most other Mycobacterium spp. are also susceptible to sparfloxacin. Interestingly, Legionella spp., including L. pneumophila, are at least as susceptible to sparfloxacin as to erythromycin; these findings correlate with results indicating activity for sparfloxacin in experimental murine models of Legionella pneumonia. Sparfloxacin is more active than ofloxacin in experimental models of Chlamydia and Mycoplasma pneumonia. Sparfloxacin penetrates extensively into tissues, as shown by its high volume of distribution (3.6 L/kg). It is about 40% bound to plasma proteins. The drug has a long elimination half-life of about 15 to 20 hours and is excreted mainly by nonrenal mechanisms. Plasma sparfloxacin concentrations are maximal within 2 to 6 hours. Peak concentrations in bronchopulmonary tissues, alveolar macrophages and sputum exceed plasma concentrations and MIC values for susceptible pathogens. Elimination of the drug is mainly via metabolism to its inactive acylglucuronide derivative and subsequent faecal excretion. Renal clearance of the parent drug and its glucuronide metabolite accounts for about 30 to 40% of total clearance. The finding that patients with moderate to severe renal failure demonstrate reduced sparfloxacin clearance has necessitated recommendations for dosage reduction in this group (see Dosage and Administration, below). In contrast, sparfloxacin pharmacokinetic s are unchanged in the elderly and in the presence of hepatic dysfunction. Sparfloxacin is effective in pneumococcal and nonpneumococcal community-acquired pneumonia, producing clinical cure in 80 to 84% of patients in several large European or multinational trials. These rates are similar to those achieved with amoxicillin, amoxicillin/clavulanic acid, erythromycin, roxithromycin, and amoxicillin plus ofloxacin in direct comparisons. Sparfloxacin has yielded clinical cure rates of 79 to 86.7% among patients with documented S. pneumoniae infections and up to 98% in patients with nonpneumococcal infection. Success rates are...