Nitrofurantoin, sold under the brand name Macrobid among others, is an antibacterial medication of the nitrofuran class used to treat urinary tract infections (UTIs), although it is not as effective for pyelonephritis.[
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Common include nausea, loss of appetite, diarrhea, and .[ Rarely numbness, lung problems, or liver toxicity may occur.][ While it appears to be generally safe during pregnancy its use is not recommended near time of parturition.][
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Nitrofurantoin was first sold in 1953.[ In 2022, it was the 158th most commonly prescribed medication in the United States, with more than 3million prescriptions.]
Medical uses
Urinary tract infections
Uses of nitrofurantoin include the treatment of uncomplicated urinary tract infections (UTIs) and prophylaxis against UTIs in people prone to recurrent UTIs.
Increasing bacterial antibiotic resistance to other commonly used agents, such as trimethoprim/sulfamethoxazole and fluoroquinolones, has led to increased interest in using nitrofurantoin in the contemporary treatment of UTIs.
In meta-analysis of , nitrofurantoin has shown clinical UTI cure rates of 79 to 92% and bacterial eradication rates of 80 to 92%.
As a prophylactic against UTIs, nitrofurantoin was similarly effective to other antibiotics, with a UTI risk ratio of 0.38.
Other bacterial infections
Nitrofurantoin is not recommended for the treatment of pyelonephritis (kidney infection),
Nitrofurantoin appears likely to minimally penetrate the prostate gland.
Antibacterial activity
Nitrofurantoin has been shown to have good activity against:
It is used in the treatment of infections caused by these organisms.
Many or all strains of the following genera are resistant to nitrofurantoin:
Special populations
Pregnancy
Nitrofurantoin is pregnancy category A in Australia.[ It is one of the few drugs commonly used in pregnancy to treat UTIs.]
Evidence of safety in early pregnancy is mixed as of 2017.[ The American College of Obstetricians and Gynecologists states that while they can be used in the first trimester other options may be preferred.][ They remain a first line treatment in the second trimester.]
Contraindications
Nitrofurantoin is contraindicated in patients with decreased renal function (CrCl < ) due to systemic accumulation and subtherapeutic levels reached in the urinary tract.
Nitrofurantoin is also contraindicated in babies up to the age of one month, as they have immature enzyme systems in their erythrocyte (glutathione instability), so nitrofurantoin must not be used because it can cause haemolytic anaemia. Nitrofurantoin is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD) because of risk of intravascular hemolysis resulting in anemia.
Adverse effects
The most common side effects of nitrofurantoin are nausea, headache, and flatulence. Less common adverse events (occurring in less than 1% of those taking the drug) include:
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Gastrointestinal: diarrhea, dyspepsia, abdominal pain, constipation, emesis
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Neurologic: dizziness, drowsiness, amblyopia
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Respiratory: acute pulmonary hypersensitivity reaction
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Allergic: pruritus, urticaria
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Dermatologic: hair loss
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Miscellaneous: fever, chills, malaise
Taken daily long-term as a prophylactic, side effects of nitrofurantoin occur at rates of 0 to 29%.
Lung toxicity
The pulmonary toxicity caused by nitrofurantoin can be categorized into acute, subacute, and chronic pulmonary reactions. The acute and subacute reactions are thought to be due to a hypersensitivity reaction and often resolve when the drug is discontinued. Acute reactions have been estimated to occur in about one in 5000 women who take the drug.
Chronic pulmonary reactions caused by nitrofurantoin include diffuse interstitial pneumonitis, pulmonary fibrosis, or both.
Liver toxicity
Liver reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely.
Neuropathy
Neuropathy is a rare side effect of taking nitrofurantoin. Patients may experience numbness and tingling in a stocking-glove pattern, which may or may not improve upon discontinuation of the drug.
Gut microflora
Nitrofurantoin has been found to modify the gut microbiota composition.
Interactions
Nitrofurantoin has historically been reported to be a disulfiram-like drug and to produce alcohol intolerance-type reactions when combined with alcohol.
Pharmacology
Organisms are said to be susceptible to nitrofurantoin if their minimum inhibitory concentration is 32 /mL or less. The peak blood concentration of nitrofurantoin following an oral dose of nitrofurantoin 100mg is less than 1μg/mL and may be undetectable. Its bioavailability is about 90% and the urinary excretion is 40%
At the concentrations achieved in urine (>100μg/mL), nitrofurantoin is a bactericide. It is bacteriostatic against most susceptible organisms at concentrations less than 32μg/mL.
Nitrofurantoin and the quinolone antibiotics are mutually antagonistic in vitro. It is not known whether this is of clinical significance.
Resistance to nitrofurantoin may be chromosomal or plasmid-mediated and involves inhibition of nitrofuran reductase.
Nitrofurantoin and its metabolites are excreted mainly by the kidneys. In renal impairment, the concentration achieved in urine may be subtherapeutic.
Mechanism of action
Nitrofurantoin is concentrated in the urine, leading to higher and more effective levels in the urinary system than in other tissues or compartments.
The drug works by damaging bacterial DNA, since its reduced form is highly reactive.
History
Nitrofurantoin has been available for the treatment of lower UTIs since 1953.[
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Society and culture
Brand names
Nitrofurantoin is marketed under many names in countries worldwide.
Animal feed
Residues from the breakdown of nitrofuran veterinary antibiotics, including nitrofurantoin, have been found in chicken in Vietnam, China, Brazil, and Thailand.
