Nitrofurantoin exerts its antibacterial effect through a unique mechanism. It is a prodrug that is activated by bacterial enzymes to form reactive intermediates. These intermediates damage bacterial DNA, proteins, and other cellular components, leading to bacterial cell death. Nitrofurantoin is primarily bacteriostatic (inhibits bacterial growth) at low concentrations and bactericidal (kills bacteria) at higher concentrations.

Nitrofurantoin is particularly effective against common uropathogens, including:

• Gram-negative bacteria: Escherichia coli, Klebsiella species, Enterobacter species.
• Gram-positive bacteria: Staphylococcus saprophyticus, Enterococcus faecalis.

It is not effective against Proteus species, Pseudomonas aeruginosa, or most Serratia species due to intrinsic resistance.

Nitrofurantoin is primarily used for the treatment and prevention of uncomplicated lower urinary tract infections (UTIs). Its clinical applications include:

1. Acute Uncomplicated Cystitis:
   • First-line treatment for uncomplicated UTIs caused by susceptible organisms.
2. Prophylaxis of Recurrent UTIs:
   • Long-term low-dose nitrofurantoin is used to prevent recurrent UTIs in patients with frequent infections.
3. Other Uses:
   • Occasionally used for the treatment of asymptomatic bacteriuria in pregnancy (if specifically indicated).

Nitrofurantoin is available in oral formulations, including immediate-release (IR) tablets, macrocrystals, and sustained-release (SR) capsules. The dosage depends on the indication and formulation.

Adults:

1. Acute Uncomplicated Cystitis:
   • Immediate-release (IR): 50–100 mg every 6 hours for 7 days.
   • Macrocrystals or sustained-release (SR): 100 mg twice daily for 7 days.
2. Prophylaxis of Recurrent UTIs:
   • Immediate-release (IR): 50–100 mg once daily at bedtime.
   • Macrocrystals or sustained-release (SR): 100 mg once daily at bedtime.

Children:

• Acute Uncomplicated Cystitis:
  • Immediate-release (IR): 1.25–1.75 mg/kg every 6 hours for 7 days.
  • Macrocrystals or sustained-release (SR): 2–2.5 mg/kg twice daily for 7 days.
• Prophylaxis of Recurrent UTIs:
  • Immediate-release (IR): 1–2 mg/kg once daily at bedtime.

Renal Impairment:

• Nitrofurantoin is contraindicated in patients with a creatinine clearance (CrCl) <60 mL/min due to reduced efficacy and increased risk of toxicity.

Nitrofurantoin is generally well-tolerated, but it can cause several adverse effects, particularly with prolonged use:

1. Gastrointestinal Effects:
   • Nausea, vomiting, diarrhea, and abdominal pain are common.
2. Pulmonary Toxicity:
   • Acute pulmonary reactions (e.g., cough, dyspnea, fever) may occur within days of starting therapy.
   • Chronic pulmonary reactions (e.g., pulmonary fibrosis) may develop with long-term use.
3. Hepatotoxicity:
   • Rare cases of hepatitis, cholestatic jaundice, and hepatic necrosis have been reported.
4. Hematologic Effects:
   • Hemolytic anemia (especially in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency).
   • Megaloblastic anemia (due to interference with folate metabolism).
5. Neurologic Effects:
   • Peripheral neuropathy (more common with prolonged use or in patients with renal impairment).
6. Allergic Reactions:
   • Rash, pruritus, and, rarely, anaphylaxis.

1. Renal Impairment:
   • Contraindicated in patients with CrCl <60 mL/min due to reduced efficacy and increased risk of toxicity.
2. G6PD Deficiency:
   • Use with caution in patients with G6PD deficiency due to the risk of hemolytic anemia.
3. Pregnancy and Lactation:
   • Avoid use near term (38–42 weeks of gestation) and during labor due to the risk of hemolytic anemia in the newborn.
   • Safe to use during early pregnancy for the treatment of asymptomatic bacteriuria.
   • Excreted in breast milk; use with caution during lactation.
4. Elderly Patients:
   • Increased risk of pulmonary and hepatic toxicity. Monitor closely.
5. Long-Term Use:
   • Monitor for pulmonary, hepatic, and neurologic toxicity in patients on long-term prophylaxis.

Nitrofurantoin has several clinically significant drug interactions:

1. Antacids Containing Magnesium Trisilicate:
   • Reduce the absorption of nitrofurantoin. Administer nitrofurantoin 1 hour before or 2 hours after antacids.
2. Probenecid:
   • Inhibits the renal excretion of nitrofurantoin, increasing the risk of toxicity.
3. Uricosuric Drugs (e.g., sulfinpyrazone):
   • May reduce the efficacy of nitrofurantoin.
4. Other Antibiotics:
   • Concurrent use with quinolones (e.g., ciprofloxacin) may reduce the efficacy of nitrofurantoin.

Nitrofurantoin is available under various generic names, including:

• Nitrofurantoin
• Nitrofurantoin Macrocrystals
• Nitrofurantoin Monohydrate/Macrocrystals

It is marketed under several brand names, such as Macrobid, Macrodantin, and Furadantin.