Gatifloxacin

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Abstract
Gatifloxacin is an 8-methoxy fluoroquinolone antibacterial agent. The drug has a broader spectrum of antibacterial activity than the older fluoroquinolones (e.g. ciprofloxacin) and shows good activity against many Gram-positive and Gram-negative pathogens, atypical organisms and some anaerobes. Notably, gatifloxacin is highly active against both penicillin-susceptible and -resistant strains of Streptococcus pneumoniae, a common causative pathogen in community-acquired pneumonia (CAP), acute sinusitis and acute bacterial exacerbations of bronchitis. Gatifloxacin is absorbed well from the gastrointestinal tract (oral bioavailability is almost 100%). Therefore, patients can be switched from intravenous to oral therapy without an adjustment in dosage. High concentrations of gatifloxacin are achieved in plasma and target tissues/fluids. Gatifloxacin has a long plasma elimination half-life, thus allowing once-daily administration. Few clinically significant interactions between gatifloxacin and other drugs have been reported. In patients with CAP, clinical response rates in recipients of intravenous/oral gatifloxacin 400 mg/day ranged from 86.8 to 98.0% and rates of bacterial eradication ranged from 83.1 to 100% (up to 28 days post-treatment). Gatifloxacin showed efficacy similar to that of amoxicillin/clavulanic acid, ceftriaxone (with or without erythromycin) with or without stepdown to clarithromycin, levo-floxacin or clarithromycin. Gatifloxacin was as effective as clarithromycin or amoxicillin/clavulanic acid, and was significantly more effective (in terms of clinical response; p < 0.035) than 7 to 10 days’ treatment with cefuroxime axetil in the treatment of acute exacerbations of chronic bronchitis. In acute sinusitis, gatifloxacin showed clinical efficacy similar to that of clarithromycin, trovafloxacin or amoxicillin/clavulanic acid. Genitourinary infections were also successfully treated with gatifloxacin. Gatifloxacin is generally well tolerated. Its tolerability profile was broadly similar to those of comparator agents in comparative trials. The most common adverse events are gastrointestinal symptoms (oral formulation) and injection site reactions. Conclusions: Gatifloxacin has an extended spectrum of antibacterial activity and provides better coverage of Gram-positive organisms (e.g. S. pneumoniae) than some older fluoroquinolones. The drug has favourable pharmacokinetic properties, is administered once daily and is at least as well tolerated as other fluoroquinolones. Gatifloxacin is a useful addition to the fluoroquinolones currently available for use in the clinical setting and has an important role in the management of adult patients with various bacterial infections. As with other fluoroquinolones, careful control of gatifloxacin usage in the community is important in order to prevent the emergence of bacterial resistance and thus preserve the clinical value of this agent. Gatifloxacin is an 8-methoxy fluoroquinolone with a 3-methylpiperazinyl substituent at C7. It has a dual site of action, inhibiting both bacterial DNA gyrase and topoisomerase IV. Gatifloxacin has a broader spectrum of antibacterial activity than those of the older fluoroquinolones, such as ciprofloxacin. The drug shows good in vitro activity against many Gram-positive and Gram-negative organisms. Atypical organisms, mycobacteria and some anaerobes are also susceptible to the drug. Gatifloxacin tended to be more active than ciprofloxacin against most Gram-positive organisms in in vitro investigations. Gatifloxacin showed good activity against a range of Gram-positive organisms according to SENTRY data (from various geographical areas including the US and Europe), with minimum concentrations inhibiting 90% of strains (MIC90) values ≤2 mg/L for S. epidermidis and 0.5 mg/L for S. pneumoniae (penicillin-susceptible or -resistant strains), viridans group and β-haemolytic streptococci. In a Canadian survey involving 4151 clinical isolates, gatifloxacin was active against most Gram-positive organisms tested (MIC90 values 0.25 to 16 mg/L) except Enterococcus faecalis (>16 mg/L) and vancomycin-resistant enterococci (32 mg/L). Gatifloxacin was more active than either ciprofloxacin or levofloxacin against 1128 Gram-positive isolates from patients with cancer. Gatifloxacin was also active against Mycoplasma hominis (MIC900.25 mg/L), Ureaplasma urealyticum (MIC900.5 mg/L), Chlamydia pneumoniae (MIC900.25 mg/L) and Mycobacterium tuberculosis (MIC90 values 0.03land 0.25 mg/L). The drug was active against a range of Enterobacteriaceae, including Escherichia coli, according to data from the SENTRY surveillance study, with MIC90 values of 0.06 to 4 mg/L. Gatifloxacin, ciprofloxacin and trovafloxacin were all very active against Haemophilus influenzae and Moraxella catarrhalis in the SENTRY survey, with 100% of organisms susceptible at breakpoint and MIC90 values ≤0.03 mg/L. In smaller in vitro studies, gatifloxacin was active against a range of other Gram-negative bacteria, including Campylobacter jejuni (MIC904 mg/L) and Legionella spp. (MIC90 0.016 to 0.03 mg/L). Gatifloxacin MIC90 values ranged from 0.25 to 4 mg/L against most anaerobes tested in four surveys (involving 92 to 351 clinical isolates), but other studies found higher MIC90 values for some Bacteroides spp. (8 to 32 mg/L). Resistance to fluoroquinolones is mediated either by changes in the target site (DNA gyrase or topoisomerase IV) or changes that reduce intracellular drug accumulation; highly fluoroquinolone-resistant bacteria require multiple mutations in several genes (including gyrA, parC and those encoding for efflux). As gatifloxacin targets both DNA gyrase and...

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