Pharmacokinetics of fosfomycin: a study in patients with prolonged treatment for urinary tract infection

Multi-drug resistant bacteria (MDRB) are an increasing worldwide problem as
recognized by the WHO. In clinical practice this leads to limited oral
antibiotic treatment options for patients with urinary tract infection (UTI).
Fosfomycin is one of the older antibiotics discovered in 1969 and is a broad
spectrum antibiotic that includes effectivity against uropathogenic
Enterobacteriaceae. As the majority of Enterobacteriaceae are still susceptible
to fosfomycin, it is a potential drug to treat UTIs with MDRB.

There are two different administration variants available of fosfomycin,
fosfomycin disodium for intravenous use and fosfomycin tromethamine and calcium
for oral use. In the Netherlands, fosfomycin tromethamine is only registered as
single dose treatment for uncomplicated urinary tract infections. Fosfomycin
disodium is recently approved in the Netherlands for treatment of systemic
infections.

Because of the potential of fosfomycin in treating MDRB, studies are conducted
to investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of
fosfomycin, especially with intravenous administration. However, robust data
upon the PK of fosfomycin is lacking (the oral formulation in particular), due
to difficulties in measuring fosfomycin levels. This leaves uncertainty about
its potency to treat systemic infections with MRDB. Recently new methods to
measure fosfomycin, including liquid chromatography * mass spectrometry, became
avalaible.

The aim of this study is to evaluate and describe the PK of fosfomycin in
individuals receiving oral treatment with multiple dosages of fosfomycin for
recurrent and/or complicatedurinary tract infection. The results of this study
will be used to validate a recently published simulation model upon the PK of
fosfomycin. In addition, the clinical and microbiological effectiveness of
prolonged treatment with fosfomycin will be evaluated in this study.

Prospective open label, cohort study

With this study we can obtain data on the pharmacokinetics of fosfomycin. In
our opinion this study provides us with the most information on the
pharmacokinetics of fosfomycin with the least possible burden for the
participants. The burden for participants are a day of visit to our clinic for
drawing blood during the day. In case participants choose to also receive an
intravenous dose of fosfomycin will this drug be the normale dose equivalent to
the oral dose they already take as prescribed. The burden for the intravenous
dose is the same as for oral except the fact that they receive the medication
intravenously. Allergic reactions are not expected because they already take
the drug.