The pharmacokinetics of fosfomycin trometamol has been assessed in 12 healthy volunteers given oral doses of 2, 3, and 4 g of fosfomycin and 3 g intravenously of fosfomycin as fosfomycin sodium, all in the fasting state. The assay was microbiological (Proteus mirabilis ATCC 21100). There was a gradual rise in both peak serum concentrations and total area under the curve by rising oral doses, from 16.0 mg/l and 106.7 mg x h/1, after 2 g to 30.9 mg/l and 189.7 mg x h/1 after 4 g respectively. The serum half-life was 4 h after the oral doses and 2.1 h after the intravenous dose. After the oral doses, the amounts excreted in urine in the active form ranged from 36 to 40% compared to 93% after the intravenous dose. The bioavailability was slightly below 40%. Concentrations in urine covers the usual urinary tract pathogens after oral doses of 2, 3, and 4 g.

Escherichia coli (E. coli) is the most commonly isolated microorganism in uncomplicated lower urinary tract infections (UTI). Due to the increased isolation of E. coli strains resistant to quinolones, it is important to have available alternative drugs to this class of antibiotics as therapy for UTIs caused by this pathogen. Among the large number of currently available antimicrobial agents, fosfomycin trometamol is a useful alternative due to its peculiar microbiological and pharmacokinetic properties. Therefore, we tested the in vitro susceptibility of 79 quinolone-resistant clinical urinary isolates of E. coli to fosfomycin trometamol in comparison with amoxicillin, chloramphenicol, cotrimoxazole, netilmicin, nitrofurantoin and tetracycline. Fosfomycin trometamol showed high activity with a MIC90 of 4 mg/l. While no strains were resistant to fosfomycin trometamol, 83.5%, 63.3%, 58.2%, and 48.1% of the isolates were resistant to tetracycline, amoxicillin, chloramphenicol and cotrimoxazole, respectively. Nitrofurantoin and netilmicin resistance was present only in 12.7% and 6.3% of the strains, respectively. In conclusion, fosfomycin trometamol has retained its activity against quinolone-resistant strains of E. coli and cross-resistance with other classes of antimicrobial agents is not presently a problem. The strains tested did present high levels of resistance to other classes of antibiotics.

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