last updated 21-12-2024

Nitrofurantoin

Nitrofurantoin

Nitrofurantoin is a bactericidal antibiotic which is drug of choice for the treatment of urinary tract infections. It covers E. coli species and enterococci.

The mechanism of action of nitrofurantoin is unique and complex. Nitrofurantoin is reduced by bacterial flavoproteins (nitrofuran reductase) to reactive intermediates, which inactivate or alter bacterial ribosomal proteins, DNA and enzymes. These inactivations or alterations cause the inhibition of vital biochemical processes of aerobic energy metabolism (pyruvate metabolism) and the syntheses of bacterial DNA, RNA, cell wall, and protein. It is not known which of the actions of nitrofurantoin is primarily responsible for its bactericidal activity.

The fact that nitrofurantoin interferes with a variety of bacterial processes may explain the lack of acquired bacterial resistance to nitrofurantoin. The multiple and simultaneous mutations of the target macromolecules that would be required to achieve resistance would probably be lethal to the bacteria. Nitrofurantoin has some interesting pharmacokinetic characteristics: oral absorption is slow (because of bad dissolution in water), while it’s renal elimination is rather rapid. This results in low plasma concentrations and high urine concentrations, exactly where the drug is needed.

Gastrointestinal complaints (nausea and vomiting), however, are the most common adverse effects. Rare, but dangerous are the acute pulmonary syndrome, acute liver failure and peripheral neuropathy. Patients should be informed that nitrofurantoin colours urine a dark orange-brown. Neonates should not be treated with nitrofurantoin, because of their immature enzyme systems in red blood cells and risk of haemolytic anaemia.

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