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These medications exert antimicrobial activity in the urine but have little or no systemic antibacterial effect. Their usefulness is limited to therapy and prevention of UTIs.


Nitrofurantoin is active against the common gram-positive urinary pathogens E faecalis and Staphylococcus saprophyticus, but the medication inhibits only about 50% of E faecium. While nitrofurantoin is active against E coli and Citrobacter, susceptibility against Proteus, Serratia, and Pseudomonas is poor. Considering its reliable activity against E coli, nitrofurantoin is one of the primary options recommended by the IDSA for the treatment of UTI. Following oral administration, about 50% of the medication is absorbed, but serum concentrations are very low and tissue levels are undetectable. Levels in the urine reach concentrations of 200–400 mcg/mL, which are well above the MICs of susceptible organisms. In kidney disease, previously defined as eGFR less than 60 mL/min/1.73 m2, subtherapeutic urine levels are present and medication accumulation takes place in serum. However, data suggest that nitrofurantoin is effective down to an eGFR of 30 mL/min/1.73 m2. Given low serum levels, poor tissue penetration, and renal elimination, the use of nitrofurantoin is limited to therapy or prophylaxis of cystitis in patients with normal kidney function. Nitrofurantoin cannot be used to treat pyelonephritis or prostatitis.

Depending on the formulation, the average daily dose in UTIs is 100 mg orally two to four times daily, taken with food. The macrocrystal preparation can be given at a dosage of 100 mg twice daily. A single daily dose of 50–100 mg can prevent recurrent UTIs in women.

Oral nitrofurantoin often causes nausea and vomiting. The crystalline formulation is better tolerated than previous preparations. Hemolytic anemia may occur in G6PD deficiency. Other side effects are skin rashes and, uncommonly, peripheral neuropathy. Acute and chronic pulmonary hypersensitivity reactions may occur, and pulmonary fibrosis has occurred with prolonged use. Called “nitrofurantoin lung,” an increased rate of this complication may follow the increased use of the medication as now recommended by national guidelines.


Fosfomycin tromethamine is a phosphonic acid derivative useful in the treatment of uncomplicated UTI. The spectrum of activity includes E coli, including ESBL-producing isolates, E faecalis, and other gram-negative aerobic urinary pathogens, but not P aeruginosa. Considering the increased resistance associated with E coli in the treatment of UTI, fosfomycin has increased its utility in this disease state. Available as a 3-g sachet, fosfomycin may be useful for the single-dose treatment of the above organisms. Like nitrofurantoin, fosfomycin should not be used for systemic infection. Five days of nitrofurantoin are superior to single-dose fosfomycin in the treatment of uncomplicated lower UTI in healthy women. Although clinical experience is limited, the ability of fosfomycin to penetrate prostatic secretions may be sufficient to use in the treatment of bacterial prostatitis. Fosfomycin disodium is available in Europe ...

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