Fosfomycin tromethamine : A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy as a single-dose oral treatment for acute uncomplicated lower urinary tract infections

• Published in: Drugs (New York, N.Y.) Vol. 53; no. 4; pp. 637 - 656
• Main Authors: PATEL, S. S, BALFOUR, J. A, BRYSON, H. M
• Format: Journal Article
• Language: English
• Published: Auckland Adis International 01.04.1997
• Subjects: Acute Disease; Administration, Oral; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Drug Administration Schedule; Female; Fosfomycin - analogs & derivatives; Fosfomycin - pharmacokinetics; Fosfomycin - pharmacology; Fosfomycin - therapeutic use; Gram-Negative Bacterial Infections - drug therapy; Gram-Negative Bacterial Infections - metabolism; Gram-Positive Bacterial Infections - drug therapy; Gram-Positive Bacterial Infections - metabolism; Humans; Medical sciences; Pharmacology. Drug treatments; Pregnancy; Randomized Controlled Trials as Topic; Tromethamine - analogs & derivatives; Tromethamine - pharmacokinetics; Tromethamine - pharmacology; Tromethamine - therapeutic use; Urinary Tract Infections - drug therapy; Urinary Tract Infections - metabolism; Human; Urinary system disease; Toxicity; Acute; Treatment efficiency; Urinary tract disease; Review; Urinary tract; In vitro; Posology; Biological activity; Fosfomycin; Infection; Resistance; Chemotherapy; Trometamol; Treatment; Animal; Bacteriosis; Clinical trial; Antibacterial agent; Pharmacokinetics; Age
• ISSN: 0012-6667; 1179-1950
• DOI: 10.2165/00003495-199753040-00007

Fosfomycin tromethamine is a phosphonic acid bactericidal agent with in vitro activity against most urinary tract pathogens. It is particularly active against Escherichia coli, and Citrobacter, Enterobacter, Klebsiella, Serratia and Enterococcus spp. There appears to be little cross-resistance between fosfomycin and other antibacterial agents, possibly because it differs from other agents in its general chemical structure and site of action. In its new formulation as the oral tromethamine salt, fosfomycin has 34 to 41% oral bioavailability, has a mean elimination half-life of 5.7 hours, and is primarily excreted unchanged in the urine. Following a single 3 g oral dose, peak urinary concentrations occur within 4 hours and remain high (> 128 mg/L) for 24 to 48 hours, which is sufficient to inhibit most urinary tract pathogens. In clinical trials in patients with acute uncomplicated lower urinary tract 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 fluoroquinolone agents, cotrimoxazole (trimethoprim-sulfamethoxazole), nitrofurantoin and pipemidic acid]. Bacteriological eradication rates of 75 to 90% were achieved 5 to 11 days after therapy, with eradication rates of 62 to 93% 4 to 6 weeks after therapy. In 3 large double-blind comparisons with ciprofloxacin, cotrimoxazole and nitrofurantoin, 99% of fosfomycin tromethamine recipients and 100% of patients receiving comparator agents were considered clinically cured or improved after therapy. 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 achieves high clinical and bacteriological cure rates in patients with acute uncomplicated lower urinary tract infection and is well tolerated. The single-dose administration regimen and favourable US pregnancy category rating of fosfomycin tromethamine should also encourage its use in this indication.