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Introduction

Urinary tract infections (UTI) affect 150 million each year, with 50-60% of women developing at least one UTI in their lifetime. Costs of these infections, ranging from societal to health care costs, are approximately $3.5 billion per year in the US alone.

Most commonly caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis. Inadequate treatment can lead to recurring symptoms, disseminating infections, and increasing bacterial resistance.

Key Points

  • UTIs affect ~150 million people/year (50–60% of women have at least one in their lifetime); most are caused by E. coli, Klebsiella, Proteus, and Enterococcus.
  • Nitrofurantoin is an IDSA first-line agent for acute uncomplicated cystitis.
  • Clinical cure rates are 88–93% and bacterial cure 81–92%, with low resistance risk and few side effects.
  • It is NOT recommended for pyelonephritis, urosepsis, or prostatitis — it does not reach therapeutic concentrations outside the urine.

Clinical Detail

Pharmacology & Dosing

PropertyDetail
Mechanism of ActionInactivation in bacterial ribosomal protein → inhibition of protein, DNA/RNA and cell wall synthesis
DoseAcute uncomplicated cystitis
  • Macrobid®: 100 mg twice daily
  • Macrodantin®: 50–100 mg every six hours
  • Duration: 5 days for women, 7 days for men

Cystitis prophylaxis

  • Macrobid®: 100 mg once daily at bedtime
  • Macrodantin®: 50–100 mg once daily at bedtime
  • Duration: 3–12 months — prolonged use has been associated with increased side effects
Susceptible bacteriaE. coli, Klebsiella, Enterococcus (including VRE), Staphylococcus saprophyticus, Enterobacter
FormulationNitrofurantoin 100 mg capsule: ~$2–6
Nitrofurantoin suspension 25 mg/5 mL, 10 mg/mL (per mL): ~$3
PK/PDDoes not reach therapeutic levels in serum or kidneys. Only concentrated in urine. Taking with food increases absorption by 40%.
Adverse effectsPeripheral neuropathy, pulmonary toxicity (extended use), hepatic dysfunction, superinfection (C. difficile), hemolytic anemia (caution if G6PD deficient)
Interactions and warningsAvoid use in CrCl < 30 mL/min (decreased efficacy and increased risk of side effects). Contraindicated in children < 1 month (risk of hemolytic anemia).
PregnancyContraindicated in pregnant patients at term (38–42 weeks gestation) and during labor/delivery (increased risk of hemolytic anemia and jaundice in the neonate). Indicated for asymptomatic bacteriuria in pregnant patients during the first trimester (Macrobid® 100 mg twice daily x 4–7 days) when other antibiotics are contraindicated or cannot be used; consider an alternative if the patient has a G6PD deficiency.
BreastfeedingAvoid in breastfeeding patients with premature infants or infants < 1 month of age, and in those with infants of any age if the patient has a G6PD deficiency. Can consider in breastfeeding patients with full-term infants > 1 month of age.
CommentsDo not use for indications other than cystitis (pyelonephritis, prostatitis, bacteremia, etc.). Commonly resistant organisms: Proteus, Pseudomonas.

Evidence

Overview of Evidence

Author, yearDesign / sample sizeIntervention & comparisonOutcome
Christiaens TC, 2002Prospective placebo-controlled RCT (n = 78)Nitrofurantoin 100 mg QID vs placebo x 3 days in females with uncomplicated UTI w/ pyuriaCombined symptom improvement and cure for nitrofurantoin — Day 3: 27/35 (p = 0.08); Day 7: 30/34 (p = 0.003). Nitrofurantoin achieved higher rates of bacteriologic cure and symptomatic relief compared to placebo.
Gupta K, 2007Prospective open-label RCT (n = 338)Nitrofurantoin 100 mg BID x 5 days vs Bactrim 1 DS tab BID x 3 daysClinical cure: nitrofurantoin 84% vs Bactrim 79% (not significant). Nitrofurantoin x 5 days = Bactrim x 3 days clinically and microbiologically.
Iravani A et al. 1999Prospective double-blind RCT (n = 521)Ciprofloxacin 100 mg BID x 3 days vs nitrofurantoin 100 mg BID x 7 days vs co-trimoxazole DS BID x 7 daysMicrobiological cure on day 3 with nitrofurantoin achieved in 127/130 (98%) of patients. Clinical resolution 4–10 days after therapy and at the 4–6 week follow-up was similar among the three treatment groups (of note, normal Cipro dosing is 500 mg daily x 3 days).
Ingalsbe ML, 2015Retrospective chart reviewMacrobid 100 mg BID or Macrodantin 50–100 mg QID, treated for 5–14 days; safety and clinical cure in males with UTIs and catheter-associated UTIsA CrCl > 60 mL/min is suggested for men to achieve an 80% cure rate for most UTIs. Cure rate with specific organisms varied with CrCl, but adverse events did not.

Conclusions

  • Nitrofurantoin is a first line recommendation per IDSA for treatment of acute uncomplicated cystitis.
  • Most studies have demonstrated a clinical cure rate with nitrofurantoin of 88%-93% and a bacterial cure rate of 81% – 92%.
  • With high rates of efficacy, low risk of resistance, and lack of side effects, nitrofurantoin is an optimal first line agent for cystitis.
  • Due to the lack of therapeutic concentration outside of the urine, nitrofurantoin is not recommended for pyelonephritis, urosepsis, or prostatitis.

References

    Flores-Mireles AL et al. Nat Rev Microbiol. 2015;13(5):269‐284.

    Al-Badr A, et al. Sultan Qaboos Univ Med J. 2013;13(3):359‐367.

    Macrobid®(Nitrofurantoin) [package insert]. Norwich Pharmaceuticals, Inc. North Norwich, NY. 2009.

    Uncomplicated Cystitis and Pyelonephritis. Clin Infect Dis. 2011. 1;52(5):e103-20.

    Nicolle LE et al. Clin Infect Dis. 2019 May 2;68(10):e83-e110.

    Christiaens TC, et al. Br J Gen Pract. 2002;52(482):729‐734.

    Gupta K, et al. Arch Intern Med. 2007;167(20):2207‐2212.

    Iravani A, et al. J Antimicrob Chemother. 1999;43 Suppl A:67‐75.

    Stein GE. Clin Ther. 1999;21(11):1864‐1872.

  • Ingalsbe ML, et al. Ther Adv Urol. 2015;7(4):186‐193.
Tags:nitrofurantoin cystitis urinary tract infection Macrobid

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