Nitrofurantoin

Nitrofurantoin is an antibacterial agent used primarily for the treatment of uncomplicated lower urinary tract infections. It achieves high concentrations in urine, but tissue penetration is limited, so it is not suitable for systemic or upper urinary tract infections.

Mechanism of action: Nitrofurantoin is a prodrug that is reduced by bacterial nitroreductases to reactive intermediates. These products damage multiple cellular targets, including ribosomal proteins and other macromolecules, thereby inhibiting essential bacterial processes. The antimicrobial effect is largely concentration-dependent in urine, and activity can vary by organism, being bacteriostatic for many pathogens and bactericidal against some.

Spectrum and indications: It is active mainly against common urinary pathogens such as Escherichia coli, Staphylococcus saprophyticus, and Enterococcus faecalis, with variable activity against Klebsiella. It has limited activity against Proteus species and is not used for kidney infections (pyelonephritis), bacteremia, or other systemic infections.

Pharmacokinetics and cautions: After oral dosing, nitrofurantoin is rapidly absorbed and concentrates in the urine, with limited systemic exposure. Renal function strongly influences urinary levels; it is generally avoided in significant renal impairment (creatinine clearance below about 60 mL/min). It is not recommended in infants under one month or in late-stage pregnancy.

Dosing and forms: Common regimens include nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days or macrocrystals 50–100 mg four times daily for 7 days, depending on the product and guidelines.

Safety and interactions: Adverse effects include nausea, vomiting, and diarrhea; dark urine is common. Rare pulmonary, hepatic, neuropathic, or hematologic toxicity can occur. Avoid in G6PD deficiency due to hemolysis risk. Absorption can be reduced by certain antacids; probenecid increases nitrofurantoin levels.