FOSFOMYCIN TROMETHAMINE - A REVIEW OF ITS ANTIBACTERIAL ACTIVITY, PHARMACOKINETIC PROPERTIES AND THERAPEUTIC EFFICACY AS A SINGLE-DOSE ORALTREATMENT FOR ACUTE UNCOMPLICATED LOWER URINARY-TRACT INFECTIONS

Fosfomycin tromethamine is a phosphonic acid bactericidal agent with i n vitro activity against most urinary tract pathogens. It is particula rly active against Escherichia coli, and Citrobacter, Enterobacter, Kl ebsiella, Serratia and Enterococcus spp. There appears to be little cr oss-resistance between fosfomycin and other antibacterial agents, poss ibly because it differs from other agents in its general chemical stru cture and site of action. In its new formulation as the oral trometham ine salt, fosfomycin has 34 to 41% oral bioavailability, has a mean el imination half-life of 5.7 hours, and is primarily excreted unchanged in the urine. Following a single 3 g oral dose, peak urinary concentra tions occur within 4 hours and remain high (>128 mg/L) for 24 to 48 ho urs, which is sufficient to inhibit most urinary tract pathogens. In c linical trials in patients,vith acute uncomplicated lower urinary trac t infection, single-dose fosfomycin tromethamine therapy was effective , and comparable with several other antibacterial agents given either as single-dose or multiple-dose treatments [e.g. beta-lactam and fluor oquinolone agents, cotrimoxazole (trimethoprim-sulfamethoxazole), nitr ofurantoin and pipemidic acid]. Bacteriological eradication rates of 7 5 to 90% were achieved 5 to 11 days after therapy, with eradication ra tes of 62 to 93% 4 to 6 weeks after therapy. In 3 large double-blind c omparisons with ciprafloxacin, cotrimoxazole and nitrofurantoin, 99% o f fosfomycin tromethamine recipients and 100% of patients receiving co mparator agents were considered clinically cured or improved after the rapy Fosfomycin tromethamine is well tolerated with a low incidence of adverse events. These comprise mainly gastrointestinal symptoms that are transient, mild and self-limiting. Thus, fosfomycin tromethamine a chieves high clinical and bacteriological cure rates in patients with acute uncomplicated lower urinary tract infection and is well tolerate d. The single-dose administration regimen and favourable US pregnancy category raring of fosfomycin tromethamine should also encourage its u se in this indication.