Fosfomycin microbiology
Fosfomycin (the active component of fosfomycin tromethamine) hasin vitroactivity against a broad range of gram-positive and gram-negative aerobic microorganisms which are associated with uncomplicated urinary tract infections. Fosfomycin is bactericidal in urine at therapeutic doses. The bactericidal action of fosfomycin is due to its inactivation of the enzyme enolpyruvyl transferase, thereby irreversibly blocking the condensation of uridine diphosphate-N-acetylglucosamine with p-enolpyruvate, one of the first steps in bacterial cell wall synthesis. It also reduces adherence of bacteria to uroepithelial cells.
There is generally no cross-resistance between fosfomycin and other classes of antibacterial agents such as beta-lactams and aminoglycosides.
Fosfomycin has been shown to be active against most strains of the following microorganisms, bothin vitroand in clinical infections as described in theINDICATIONS AND USAGEsection:
Aerobic gram-positive microorganisms
Enterococcus faecalis
Aerobic gram-negative microorganisms
Escherichia coli
The followingin vitrodata are available,but their clinical significance is unknown.
Fosfomycin exhibitsin vitrominimum inhibitory concentrations (MIC's) of 64 g/mL or less against most ( 90%) strains of the following microorganisms; however, the safety and effectiveness of fosfomycin in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials:
Aerobic gram-positive microorganisms
Enterococcus faecium
Aerobic gram-negative microorganisms
Citrobacter diversus
Citrobacter freundii
Enterobacter aerogenes
Klebsiella oxytoca
Klebsiella pneuomoniae
Proteus mirabilis
Proteus vulgaris
Serratia marcescens

# SUSCEPTIBILITY TESTING
Dilution Techniques:
Quantitative methods are used to determine minimum inhibitory concentrations (MIC's). These MIC's provide estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure uses a standardized agar dilution method1or equivalent with standardized inoculum concentrations and standardized concentrations of fosfomycin tromethamine (in terms of fosfomycin base content) powder supplemented with 25 g/mL of glucose-6-phosphate.BROTH DILUTION METHODS SHOULD NOT BE USED TO TEST SUSCEPTIBILITY TO FOSFOMYCIN.The MIC values obtained should be interpreted according to the following criteria:
A report of "susceptible" indicates that the pathogen is likely to be inhibited by usually achievable concentrations of the antimicrobial compound in the urine. A report of "intermediate" indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "resistant" indicates that usually achievable concentrations of the antimicrobial compound in the urine are unlikely to be inhibitory and that other therapy should be selected.
Standardized susceptibility test procedures require the use of laboratory control microorganisms. Standard fosfomycin tromethamine powder should provide the following MIC values for agar dilution testing in media containing 25 g/mL of glucose-6-phosphate..
Diffusion Techniques:
Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial agents. One such standardized procedure2requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 200-g fosfomycin and 50-g of glucose-6-phosphate to test the susceptibility of microorganisms to fosfomycin.
Reports from the laboratory providing results of the standard single-disk susceptibility tests with disks containing 200 g of fosfomycin and 50 g of glucose-6-phosphate should be interpreted according to the following criteria:
Interpretation should be stated as above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for fosfomycin.
As with standardized dilution techniques, diffusion methods require use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 200-g fosfomycin disk with the 50-g of glucose-6-phosphate should provide the following zone diameters in these laboratory quality control strains: