Nitrofurantoin, sold under the brand name Macrobid among others, is an antibacterial medication of the nitrofuran class. It is used primarily to treat lower urinary tract infections (UTIs) but it is also used in bladder infections. It is not indicated for kidney infections nor is it as effective for them. It is taken by mouth. Common side effects include nausea, loss of appetite, diarrhea, and headaches. Rarely numbness, lung problems, or liver problems may occur. While it appears to be generally safe during pregnancy its use is not recommended near time of delivery. While it usually works by slowing bacterial growth, it may result in bacterial death at the high concentrations found in urine, provided forced fluid dilution of urine is avoided. As the name or branding suggests, nitrofurantoin (due to the brand name macrobid) should be taken twice per day, or bis in die (B.I.D.). Nitrofurantoin was first sold in 1953. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2023, it was the 143rd most commonly prescribed medication in the United States, with more than 3 million 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. It is a first-line therapy for acute uncomplicated cystitis. It is not recommended for empiric treatment of hospital-acquired 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. The efficacy of nitrofurantoin in treating UTIs combined with a low rate of bacterial resistance to this agent makes it one of the first-line agents for treating uncomplicated UTIs as recommended by the Infectious Diseases Society of America and the European Society of Clinical Microbiology and Infectious Diseases. In meta-analyses of clinical trials, nitrofurantoin has shown clinical UTI cure rates of 79 to 92% and bacterial eradication rates of 80 to 92%. Treatment with nitrofurantoin for 7 days was not more effective than treatment for 5 days, whereas treatment for 5 days was superior to treatment for 3 days (which showed clinical cure rates of 61–70%). The effectiveness of nitrofurantoin for 5 days is equivalent to that with single-dose fosfomycin. As a prophylactic against UTIs, nitrofurantoin was similarly effective to other antibiotics, with a UTI risk ratio of 0.38. Taken daily long-term as a prophylactic, there were no differences in effectiveness between different doses of nitrofurantoin (50 mg/day, 75 mg/day, 100 mg/day, or 50 mg twice daily). Although similarly effective as other antibiotics, prophylactic nitrofurantoin showed an increased risk of adverse effects compared to other antibiotics (risk ratios = 2.17 to 2.24). The adverse effects of nitrofurantoin were mostly gastrointestinal in nature.
Other bacterial infections Nitrofurantoin is not recommended for the treatment of pyelonephritis (kidney infection), and intra-abdominal abscess, because of extremely poor tissue penetration and low blood levels. Nitrofurantoin appears likely to minimally penetrate the prostate gland. As such, nitrofurantoin is not recommended for eradication of chronic bacterial prostatitis. In any case, in men with antibiotic-refractory or relapsing chronic bacterial prostatitis, prophylactic nitrofurantoin may be useful in preventing UTIs and managing symptoms. However, supporting data were lacking as of 2020.
Antibacterial activity Nitrofurantoin has been shown to have good activity against:
Escherichia coli Staphylococcus species Enterococcus species Klebsiella species (mixed) Citrobacter species Coagulase negative staphylococci Bacillus subtilis species Streptococcus agalactiae It is used in the treatment of infections caused by these organisms. Many or all strains of the following genera are resistant to nitrofurantoin:
Enterobacter species (mixed) Proteus species Pseudomonas species Acinetobacter species Morganella species Serratia species Providencia species
Special populations
Pregnancy Nitrofurantoin is pregnancy category A in Australia. It is one of the few drugs commonly used in pregnancy to treat UTIs. There is a potential risk of hemolytic anemia in the newborn when used near time of delivery. Newborns of women given this drug late in pregnancy had a higher risk of developing neonatal jaundice. 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. A 2015 meta analysis found no increased risk from first trimester use in cohort studies that was a slight increase of malformations in case control studies.
Contraindications Nitrofurantoin is contraindicated in patients with decreased renal function (CrCl < 60 ml/min) due to systemic accumulation and subtherapeutic levels reached in the urinary tract. However, a retrospective chart review suggests the data for this cutoff are slim and a cutoff of CrCl < 40 ml/min would be more appropriate. Many of the severe side effects of this drug are more common in the elderly and those with renal impairment, as this causes the drug to be retained in the body and reach higher systemic levels. Thus, the drug is not recommended for the elderly population according to 2012 AGS Beers Criteria. Nitrofurantoin is also contraindicated in babies up to the age of one month, as they have immature enzyme systems in their red blood cells (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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