Nitrofurantoin for Uncomplicated Cystitis

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  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)

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

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.