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Proteus mirabilis | 2nd line |
Proteus vulgaris | 2nd line |
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Aerobic gram-positive cocci | |
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PHARMACOLOGY![[Top]](images/m/top.gif)
MECHANISM
Fosfomycin interferes with bacterial wall synthesis by inhibiting the enzyme enolpyruvyl transferase (this enzyme catalyzes the formation of uridine diphosphate N-acetylmuramic acid which is the first step of bacterial cell wall synthesis).
PHARMACOKINETIC PARAMETERS
Absorption
30% absorbed with food; 37% absorbed without food.
Metabolism and Excretion
Converted to free acid fosfomycin. Excreted primarily in the urine. 18% excreted in the feces.
Protein Binding
No protein binding.
Cmax, Cmin, and AUC
64-128 mcg/ml; 3000 mcg/ml with a 3-g oral dose achieved in the urine.
T1/2
5.7 hrs
Distribution
Distributed into bladder wall, kidneys, prostate and seminal vesicles.
PREGNANCY RISK
B-Animal data shows no teratogenic effects. Several published reports studied the efficacy and safety of oral fosfomycin in all stages of pregnancy. In these studies fosfomycin did not cause harm to the fetus.
BREAST FEEDING COMPATIBILITY
No data, but expect excretion into breast milk due to low molecular weight of fosfomycin.
COMMENTS
Oral agent FDA approved only for uncomplicated UTI. Broad spectrum of activity includes all common uropathogenic bacteria. Single dose therapy (3 gram) was equivalent to 7-day course of norfloxacin in randomized, blinded study. May be used for VRE in UTIs if renal function is good. Due to limited systemic absorption, fosfomycin should not be used for severe pyelonephritis and urosepsis.
References
- Minassian MA et al: A comparison between single-dose fosfomycin trometamol (Monuril) and a 5-day course of trimethoprim in the treatment of uncomplicated lower urinary tract infection in women. Int J Antimicrob Agents 10:39, 1998 [PMID:9624542]
Comment: Fosfomycin is a relatively expensive (AWP=$35/3gm sachet) alternative to TMP-SMX for the treatment of acute cystitis in women. An advantage is the single dose versus a 3 day treatment regimen
- Patel SS, Balfour JA, Bryson HM: 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. Drugs 53:637, 1997 [PMID:9098664]
Comment: Comprehensive review of drug relative to treatment of UTI.
- Russell PJ et al: Growth and metastasis of human bladder cancer xenografts in the bladder of nude rats. A model for intravesical radioimmunotherapy. Urol Res 19:207, 1991 [PMID:1926654]
Comment: Single dose fosfomycin was equivalent to norfloxacin in females with uncomplicated UTI.
- Naber KG, Thyroff-Friesinger U: Fosfomycin trometamol versus ofloxacin/co-trimoxazole as single dose therapy of acute uncomplicated urinary tract infection in females: a multicentre study. Infection 18 Suppl 2:S70, 1990 [PMID:2286465]
Comment: Fosfomycin as single-dose therapy was compared with ofloxacin and trimethoprim-sulfamethoxazole, each also given as single-dose therapy; fosfomycin was significantly less effective in eradicating initial bacteriuria than was ofloxacin (135 [70%] of 194 vs. 92 [86%] of 107; P , .001). IDSA guidelines recommends fosfomycin as an alternative therapy for the treatment of uncomplicated urinary tract infection resistant to TMP/SMX.
- Bayrak O, Cimentepe E, Inegöl I, et al.; Is single-dose fosfomycin trometamol a good alternative for asymptomatic bacteriuria in the second trimester of pregnancy?; Int Urogynecol J Pelvic Floor Dysfunct.; Vol. 18; pp. 525-529; ISSN: 16941068;
Comment: Fosfomycin x1 was as safe and effective as cefuroxime x 5d in 2nd trimester pregnant women with asymptomatic bacteriuria.
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