Uncomplicated UTI Agents

GENERAL PRINCIPLES

Nitrofurantoin and oral fosfomycin are unique in their pharmacokinetic profiles, which result in high urinary, but minimal blood concentrations. These agents should only be used in the treatment of uncomplicated UTIs and should not be used for pyelonephritis or other systemic infections.

TREATMENT

• Nitrofurantoin (50-100 mg PO macrocrystals q6h or 100 mg PO dual-release formulation q12h for 5 d) is metabolized by bacteria into toxic intermediates that inhibit multiple bacterial processes, resulting in bactericidal activity. The agent is indicated for the treatment of uncomplicated UTIs except those caused by Proteus, P. aeruginosa, Morganella, or Serratia. Notably, nitrofurantoin can also be effective for uncomplicated VRE UTIs. Nitrofurantoin should be avoided in patients with renal dysfunction due to increased adverse events (outlined below).

• Fosfomycin (3 g sachet dissolved in cold water PO once) is a bactericidal oral antibiotic that kills bacteria by inhibiting an early step in cell wall synthesis. It has a spectrum of activity that includes most urinary tract pathogens, including P. aeruginosa, enterococci (including VRE), and some MDR Enterobacterales. Oral fosfomycin is most useful for treating uncomplicated UTIs caused by susceptible strains of E. coli or E. faecalis.

SPECIAL CONSIDERATIONS

• Adverse events for nitrofurantoin consist primarily of nausea, which can be mitigated by taking with food. Rarely, neurotoxicity, hepatotoxicity, and pulmonary fibrosis, especially with prolonged use in the setting of renal dysfunction. Thus, it should not be used in patients with CrCl lt;30 mL/min. Patients should be warned that their urine may become brown secondary to the medication. Probenecid decreases the concentration of nitrofurantoin in the urine and should be avoided.

• Adverse events for fosfomycin include diarrhea. It should not be taken with metoclopramide, which interferes with fosfomycin absorption.