Ofloxacin

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Abstract
Ofloxacin is an established fluoroquinolone agent which achieves good concentrations in genitourinary tract tissues and fluids. It has good in vitro activity against most Enterobacteriaceae, Staphylococcus saprophyticus, methicillinsusceptible S. aureus, Neisseria gonorrhoeae, Chlamydia trachomatis and Haemophilus ducreyi, intermediate activity against Ureaplasma urealyticum and most enterococci, but limited or no in vitro activity against enterococci, Serratia marcescens, Pseudomonas aeruginosa and many anaerobes. However, high concentrations achieved in the urine ensure its activity against most urinary tract pathogens. Ofloxacin demonstrates consistent efficacy in a broad range of urinary tract infections, achieving bacteriological response rates in excess of 80% in uncomplicated and 70% in complicated infections. The efficacy of ofloxacin was similar to that of all comparators tested including other fluoroquinolones, cephalosporins and cotrimoxazole (trimethoprim/sulfamethoxazole). Ofloxacin is also effective as a single-dose regimen in the treatment of uncomplicated gonorrhoea, as a 7-day regimen in uncomplicated C. trachomatis infections, and as monotherapy in uncomplicated pelvic inflammatory disease (PID). Again, ofloxacin demonstrated similar efficacy to alternative treatments in each type of infection. The availability of an intravenous formulation and near-complete oral bioavailability allow ofloxacin to be administered as a sequential regimen without loss of activity. The tolerability and drug interaction profile of ofloxacin is consistent with that of other fluoroquinolones. The most commonly reported adverse events with ofloxacin are gastrointestinal, neurological and dermatological. It was associated with a lower incidence of photosensitivity and tendinitis and higher incidence of some neurological events than some other fluoroquinolones. Ofloxacin seems to have a lower propensity to interact with xanthines than other fluoroquinolones. Conclusion: Ofloxacin has established efficacy in the treatment of a wide variety of urinary tract infections, although, like other fluoroquinolones, it should be used rationally to preserve its activity. Currently, ofloxacin also holds an importantplace among fluoroquinolones in the treatment of C. trachomatis infections and uncomplicated PID, although its acceptance as monotherapy in PID is likely to depend on clarification of the causative role of anaerobic pathogens in this infection. Considering pathogens of the genitourinary tract, ofloxacin has good in vitro activity against most Enterobacteriaceae, S. saprophyticus, methicillin-susceptible S. aureus, N. gonorrhoeae, C. trachomatis and H. ducreyi [median minimum concentration required to inhibit 90% of strains (MIC90) ≤2 mg/L]. Although ofloxacin is active against Providencia spp., strains from some centres were intermediately susceptible or resistant to the agent. Ofloxacin has intermediate in vitro activity against most enterococci and Ureaplasma urealyticum (median MIC90 ≥4 mg/L) and limited or no in vitro activity against Serratia marcescens, Pseudomonas aeruginosa, Bacteroides fragilis and many other anaerobes (median MIC90 ≥8 mg/L). However, ofloxacin achieves high urinary concentrations (282 to 547 mg/L) and therefore is clinically active against most urinary tract pathogens. Ofloxacin has 2 main metabolites (desmethyl ofloxacin and ofloxacin N-oxide) with antibacterial activity, but they are generally less active than ofloxacin. Compared with other fluoroquinolones, ofloxacin has similar or better in vitro activity against urinary tract pathogens, N. gonorrhoeae and H. ducreyi but less activity than trovafloxacin against C. trachomatis. The superior absorption profile of ofloxacin versus ciprofloxacin means that ofloxacin may have a comparative advantage against some pathogens (e.g. C. trachomatis and some Grampositive bacteria). In humans, ofloxacin causes significant suppression of the aerobic intestinal flora but has little effect on the anaerobic intestinal microflora. Microflora had almost returned to normal 1 week after treatment and had completely normalised 4 weeks after treatment. Ofloxacin is almost completely absorbed after oral administration, with tablet formulations having almost 100% bioavailability. Maximum plasma concentrations (Cmax) are attained within 1 to 2 hours of oral administration and are linearly related to dose. A 200mg oral dose produces serum concentrations of 2.6 mg/L in healthy volunteers. The rate, but not the extent, of absorption may be reduced by food intake. Intravenous administration may produce Cmax values up to 50% higher than the oral route, but these are followed by a rapid decline, so subsequent plasma concentrations are similar for both routes. As with most other fluoroquinolones, ofloxacin exhibits low plasma protein binding (20 to 25%) and extensive penetration into body tissues and fluids. After therapeutic doses, concentrations of ofloxacin in female genitourinary tissues and fluids and prostatic and kidney tissue are similar to, or greater than, those in plasma. Concentrations in prostatic fluid were only one-third of plasma...