- 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.
|Mechanism of Action||Inactivation in bacterial ribosomal protein→inhibition of protein, DNA/RNA and cell wall synthesis|
|Dose||Acute uncomplicated cystitis o Macrobid® :100 mg twice daily ß On Grady formulary o Macrodantin® : 50-100mg every six hours o Duration: 5 days for women, 7 days for men Cystitis Prophylaxis o Macrobid® : 100mg once daily at bedtime o Macrodantin® : 50-100mg once daily at bedtime o Duration: 3-12 months – prolonged use has been associated with increased side effects|
|Susceptible bacteria||• E. Coli, Klebsiella, Enterococcus (including VRE), Staphylococcus Saprophyticus, Enterobacter|
|Formulation||Nitrofurantoin 100mg capsule: ~$2-6 Nitrofurantoin suspension 25mg/5mL, 10mg/mL (per mL): ~$3|
|PK/PD||Does not reach therapeutic levels in serum or kidneys. Only concentrated in urine. Taking with food increases absorption by 40%|
|Adverse Effects||Peripheral neuropathy, pulmonary toxicity (extended use) Hepatic dysfunction, superinfection (C. Difficile), hemolytic anemia (caution if G6PD deficient)|
|Interactions and warnings||Avoid use in CrCl < 30mL/min (decreased efficacy and increased risk of side effects) Contraindicated in children < 1 month (risk of hemolytic anemia)|
|Pregnancy||Contraindicated in pregnant patients at term (38-42 weeks gestation), during labor/delivery o Increased risk of hemolytic anemia and jaundice developing in neonateIndicated for asymptomatic bacteriuria in pregnant patients during first trimester o Macrobid® : 100mg twice daily x 4-7 days o Use if other antibiotics are contraindicated or cannot be utilized o Consider alternative if pregnant patient has a G6PD deficiency|
|Breastfeeding||Avoid in: o Breastfeeding patients with premature infants or < 1 month of age o Breastfeeding patients with infants of any age if patient has G6PD deficiency Can consider: o Breastfeeding patients with full-term infants > 1 month of age|
|Comments||Do not use for indication other than cystitis (pyelonephritis, prostatitis, bacteremia etc.) Commonly resistant organisms: Proteus, Pseudomonas|
Jlpruitt@gmh.edu; kmfifer@GMH.EDU> For educational purposes only
|Overview of Evidence|
|Author, year||Design/ sample size||Intervention & Comparison||Outcome|
|Christiaens TC, 2002||Prospective RCT- placebo controlled (n = 78)||Nitrofurantoin 100mg QID vs placebo x 3 days in females with uncomplicated UTI w/ pyuria||Combined sx improvement and cure for Nitrofurantoin Day 3: 27/35 (p = 0.08) Day 7: 30/34 (p= 0.003) Nitrofurantoin achieved higher rate of bacteriologic cure and symptomatic relief compared to placebo|
|Gupta K, 2007||Prospective open label RCT (n = 338)||Nitrofurantoin 100mg BID x 3 days vs Bactrim 1 DS tab BID x 3 days||Clinical Cure: Nitrofurantoin 84% vs. Bactrim 79% (not significant) Microbiological cure on day 3 of nitrofurantoin achieved in 127/130 (98%) of patients Nitrofurantoin x 5 days = Bactrim x 3 days clinically and microbiologically|
|Irvani A et al. 1999||Prospective double blind RCT (n = 521)||Cipro 100mg BID x 3 days Nitrofurantoin 100mg BID x 7 days Co-trimoxazole DS BID x 7 days||Clinical resolution 4- 10 days after therapy and at the 4- 6 week followup was similar among the three treatment groups. (of note, normal dosing with Cipro is 500mg daily x3 days)|
|Ingalsbe ML, 2015||Retrospective chart review||Macrobid 100mg BID Macrodantin 50-100mg QID Treated for 5-14 days Safety and clinical cure in males with UTIs and catheter-associated UTIs||A CrCl of > 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|
- 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.
- 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.