Fosfomycin dosing

Fosfomycin comes in dry fonn as a one-dose packet to be dissolved in 90 to 120 mL water (not hot water). Drink immediately after mixing and take with food to prevent gastric upset. 

Fosfomycin (Monurol) [Antibiotic] Uses Uncomplicated UTl Action -1- CeU w l synth Dose 3 g PO in 90-120 mL of H2O single dose X in renal impair Caution [B, ] -t Absorption w/ antacids/Ca salts Contra Component sensitivity Disp Granules SE HA, GI upset Interactions X Effects W/ antacids, metoclopramide EMS Monitor ECG and BP for signs of hypovolemia and electrolyte disturbances d/t D OD May cause impaired coordination, hearing loss and bitt taste in mouth symptomatic and supportive... 

Symptoms should improve 2-3 days after the initial dose of fosfomycin... 

Fosfomycin trometamol is available in both oral and parenteral formulations, although only the oral preparation is approved for use in the USA. Oral bioavailability is approximately 40%. Peak serum concentrations are 10 mcg/mL and 30 mcg/mL following a 2-g or 4-g oral dose, respectively. The half-life is approximately 4 hours. The active drug is excreted by the kidney, with urinary concentrations exceeding MICs for most urinary tract pathogens. 

Fosfomycin is approved for use as a single 3-g dose for treatment of uncomplicated lower urinary tract infections in women. The drug appears to be safe for use in pregnancy. 

Fosfomycin has relatively low toxicity. Its penetration into tissues, including bones and joints, and into the cerebrospinal fluid is good. When given orally (2-3 g/day), it can produce gastrointestinal distress when injected intramuscularly, it can cause local pain. Fosfomycin is recommended in daily doses of 4-16 g intravenously for the treatment of severe infections resistant to other commonly used antibiotics. Fosfomycin diffuses moderately well into bone tissue (2). 

In a multicenter trial in 749 ambulatory women aged at least 12 years with an acute uncomplicated urinary tract infection, a single dose of fosfomycin tromethamine 3 g had an equivalent bacteriological and clinical cure rate as a 7-day course of nitrofurantoin (4). Adverse events were reported by 5.3% of fosfomycin-treated patients (versus 5.6%). The most common adverse effects were diarrhea (2.4%), vaginitis (1.8%), and nausea (0.8%), and 1.9% of fosfomycin-treated patients were withdrawn owing to adverse events (versus 4.3%). 

Stein GE. Comparison of single-dose fosfomycin and a 7-day conrse of nitrofurantoin in female patients with uncomplicated urinary tract infection. Clin Ther 1999 21(ll) 1864-72. 

A unique and peculiar adverse reaction related to the rapid infusion of large doses is the so-caUed red neck or red man sjmdrome. It is the most common adverse reaction to vancomycin, characterized by fever, chills, paresthesia, and eiythema at the base of the neck and the upper back, and can be followed by a hypotensive episode (12). It is not a true allergic reaction. It seems to be due to vancomycin-induced release of histamine and possibly other vasoactive substances without the involvement of preformed antibodies (13,14). In rat peritoneal mast cells vancomycin provoked histamine release dose-dependently fosfomycin inhibited this effect (15). 

Fosfomycin is a broad-spectrum, bactericidal antibacterial that inhibits the growth of E. coli. S. aureii.s, and Sernttia, Klebsiella, Cilmhucler, Enleroaiccus. and Enterohacter spp. at a concentration less than 64 mg/L. Currently fosfo-niycin i.s recommended as single-dose therapy for uncomplicated urinary tract infections. It possesses in vitro efficacy similar to that of norfloxacin and trimcthoprim-sulfamethox-a/.ole. 

Fosfomycin Parenteral Therapy Aminoglycosides Gentamicin Tobramycin Amikacin Netilmicin Single-dose therapy for uncomplicated infections. Gentamicin and tobramycin are equally effective gentamicin is less expensive. Tobramycin has better pseudomonal activity, which may be important in serious systemic infections. Amikacin generally is reserved for multiresistant bacteria. 

Many urinary tract infections are caused by sulfonamide-resistant microorganisms. Trimethoprim-sulfamethoxazole, a quinolone, trimethoprim, fosfomycin, or ampicillin are the preferred agents. Sulfisoxazole may be used in areas where the prevalence of resistance is not high or when the organism is known to be sensitive. The usual dose is 2-4 g initially, followed by 1-2 g, orally four times a day for 5—10 days. Patients with acute pyelonephritis should not be treated with a sulfonamide. 

Fosfomycin is excreted by the kidney, with urinary levels exceeding the minimal inhibitory concentrations (MiCs) for many urinaiy tract pathogens. In a single dose, the drug is less effective than a 7-day course of treatment with fluoroquinolones. With multiple dosing, resistance emerges rapidly and diarrhea is common. Fosfomycin may be synergistic with beta-lactam and quinolone antibiotics in specific infections. 

Immunofluorescent microscopic examination of fluid expressed from the penile chancre of this patient revealed treponemes. Since he appears to be infected with T pallidu))i, the best course of action would be to (A) Treat with spectinomycin Treat with oral tetracycline Inject intramuscular benzathine penicillin G Give a single oral dose of fosfomycin... 

In a study in 9 healthy subjects the pharmacokinetics of a 50-mg dose of fosfomycin were not significantly altered by two 400 mg doses of cimetidine, given both the night before and 30 minutes before the fosfomycin. ... 

Metoclopramide 20 mg given to 9 healthy subjects 30 minutes before fosfomycin 50 mg/kg reduced the peak serum levels of fosfomycin by 42% and reduced the AUC by 27%. These changes appear to occur because metoclopramide speeds the transit through the gut, so that less time is available for good absorption. However, despite these reductions, the urinary concentrations of fosfomycin remained above the minimum levels required for common urinary pathogens for at least 36 hours after the dose. This suggests that the interaction is unlikely to be clinically important. 

Among the side effects reported from oral treatment with fosfomycin in these doses have been diarrhoea and other disturbances of the gastrointestinal tract, transient increases of serum GOT, GPT and LDH, exanthemata and rash, eosinophilia (in one case) and derangement of vision (59 ). 

Parenteral administration of fosfomycin (as sodium salt) has also been practised, in amounts of as much as 4—8 g im. daily, and 148-410 mg/kg/day iv. for 6 days (58, 60 ). The tolerance for fosfomycin was acceptable when it was given intramuscularly in patients with osteomyelitis, though the injection was on the whole somewhat painful (58 ). On the other hand, intravenous administration of high doses to 21 seriously ill paediatric patients caused pain in 7 of them, and occasionally also vomiting, itching of the skin and transient increases of serum transaminases. The efficacy of the treatment from the clinical viewpoint was low (60 -). 

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