Nitrofurantoin

Common indications

• Uncomplicated lower urinary tract infection (UTI), as a first-line antibiotic (alternatives are trimethoprim, amoxicillin). Nitrofurantoin is particularly suited to the treatment of UTI as it is effective against the common causative organisms, reaches therapeutic concentrations in urine through renal excretion, and is most bactericidal in acidic environments such as urine.

 

Mechanisms of action

• Nitrofurantoin is metabolised (reduced) in bacterial cells by nitrofuran reductase. 
• Its active metabolite damages bacterial DNA and causes cell death (bactericidal effect). 
• Nitrofurantoin is active against the Gram-negative (e.g. Escherichia coli) and Gram-positive (Staphylococcus saprophyticus) organisms that commonly cause urinary tract infections. 
• Bacteria with reduced nitrofuran reductase activity are resistant to nitrofurantoin. 
• Some organisms that are less common causes of urinary tract infection (such as klebsiella and proteus species) have intrinsic resistance to nitrofurantoin. 
• It is relatively rare for E. coli to acquire nitrofurantoin resistance.

 

Important adverse effects

• As with many antibiotics, nitrofurantoin can cause gastrointestinal upset (including nausea and diarrhoea) and immediate and delayed hypersensitivity reactions (see Penicillins, broad-spectrum). 
• Nitrofurantoin specifically can turn urine dark yellow or brown. 
• Less commonly, it may cause chronic pulmonary reactions (including inflammation [pneumonitis] and fibrosis), hepatitis and peripheral neuropathy, which all are more likely with prolonged administration. 
• In neonates, haemolytic anaemia may occur because immature red blood cells are unable to mop up nitrofurantoin-stimulated superoxides, which damage red blood cells.

 

Warnings

• Nitrofurantoin should not be prescribed for pregnant women towards term or for babies in the first 3 months of life. 
• It is contraindicated in patients with renal impairment, as impaired excretion increases toxicity and reduces efficacy due to lower urinary drug concentrations. 
• Caution is required when using nitrofurantoin for long-term prevention of UTIs, as chronic use increases the risk of adverse effects, particularly in elderly patients.

 

Important interactions

• There are no significant interactions between nitrofurantoin and other commonly prescribed drugs.