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Charleston, SC

jimmy@pharmacyfridaypeals.com

Cystitis Treatment with Nitrofurantoin

Introduction

  1. Urinary tract infections (UTI) affect 150 million each year, with 50-60% of women developing at least one UTI in their lifetime.
  2. Costs of these infections, ranging from societal to health care costs, are approximately $3.5 billion per year in the US alone.
  3. Most commonly caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis.
  4. Inadequate treatment can lead to recurring symptoms, disseminating infections, and increasing bacterial resistance.
 Pharmacology
Mechanism of ActionInactivation in bacterial ribosomal protein→inhibition of protein, DNA/RNA and cell wall synthesis
DoseAcute 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
FormulationNitrofurantoin 100mg capsule: ~$2-6 Nitrofurantoin suspension 25mg/5mL, 10mg/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 < 30mL/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), 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
BreastfeedingAvoid 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
CommentsDo 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, yearDesign/ sample sizeIntervention & ComparisonOutcome
Christiaens TC, 2002Prospective 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 daysClinical 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 daysClinical 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, 2015Retrospective chart reviewMacrobid 100mg BID Macrodantin 50-100mg QID   Treated for 5-14 days   Safety and clinical cure in males with UTIs and catheter-associated UTIsA 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

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

  1. Flores-Mireles AL et al. Nat Rev Microbiol. 2015;13(5):269‐284.  
  2. Al-Badr A, et al. Sultan Qaboos Univ Med J. 2013;13(3):359‐367.  
  3. Macrobid®(Nitrofurantoin) [package insert]. Norwich Pharmaceuticals, Inc. North Norwich, NY. 2009.
  4. Uncomplicated Cystitis and Pyelonephritis. Clin Infect Dis. 2011. 1;52(5):e103-20.
  5. Nicolle LE et al. Clin Infect Dis. 2019 May 2;68(10):e83-e110.
  6. Christiaens TC, et al. Br J Gen Pract. 2002;52(482):729‐734.
  7. Gupta K, et al. Arch Intern Med. 2007;167(20):2207‐2212.  
  8. Iravani A, et al. J Antimicrob Chemother. 1999;43 Suppl A:67‐75.
  9. Stein GE. Clin Ther. 1999;21(11):1864‐1872.
  10. Ingalsbe ML, et al. Ther Adv Urol. 2015;7(4):186‐193.  

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