Fosfomycin trometamol: activity in vitro against urinary tract pathogens
1Department of Microbiology, Queen's Medical Centre, Nottingham, United Kingdom.
Abstract:
The spectrum of activity of fosfomycin embraces all the common causes of uncomplicated urinary tract infection. The activity is greatly affected by the conditions of the test. Glucose, phosphates and NaCl all interfere with the activity of the drug, whereas glucose-6-phosphate has a marked potentiating effect against many strains. The activity of fosfomycin is greater at acid than at alkaline pH; inoculum density also has an effect, but this is less marked at acid pH values. Fosfomycin is rapidly bactericidal to susceptible bacteria, causing lysis within 30 min. In contrast, fosmidomycin, which also has a narrower spectrum of activity than fosfomycin, is much more slowly bactericidal. In the form of its trometamol salt, fosfomycin is well absorbed after oral administration, and is excreted in high concentration in the urine. Experiments in an in-vitro model of the treatment of bacterial cystitis suggest that concentrations of fosfomycin achievable in urine after oral administration of high doses of the trometamol salt have a marked suppressive effect on bacterial growth without favouring the emergence of resistant mutants.
Insights
Fosfomycin effectively treats uncomplicated urinary tract infections by rapidly killing bacteria. Oral administration of its trometamol salt results in high urinary concentrations, suppressing bacterial growth without promoting resistance.
Area of Science:
- Pharmacology and Microbiology
- Antimicrobial Agents
Background:
- Fosfomycin exhibits broad-spectrum activity against common urinary tract infection pathogens.
- Antimicrobial activity is influenced by various in vitro conditions, including pH and the presence of specific substances.
Purpose of the Study:
- To evaluate the activity spectrum and influencing factors of fosfomycin.
- To assess the pharmacokinetic profile and efficacy of fosfomycin trometamol in treating bacterial cystitis.
Main Methods:
- In vitro testing of fosfomycin against common urinary tract pathogens under varying conditions (pH, glucose, phosphates, NaCl, glucose-6-phosphate).
- Assessment of bactericidal kinetics and comparison with fosmidomycin.
- In vitro model of bacterial cystitis using fosfomycin trometamol after oral administration.
Main Results:
- Fosfomycin's activity is affected by test conditions; glucose-6-phosphate potentiates its effect.
- Activity is greater at acidic pH and with lower inoculum density.
- Fosfomycin is rapidly bactericidal; fosmidomycin is slower.
- Fosfomycin trometamol is well-absorbed orally and excreted in high urinary concentrations.
- Achieved urinary concentrations suppressed bacterial growth in an in vitro cystitis model without resistance emergence.
Conclusions:
- Fosfomycin is a potent antimicrobial for uncomplicated urinary tract infections, with its efficacy influenced by environmental factors.
- Fosfomycin trometamol demonstrates favorable pharmacokinetics and in vitro efficacy for treating bacterial cystitis, suggesting potential for managing urinary tract infections without promoting resistance.
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