Tools for Practice


#270 Burning Evidence for Fosfomycin in Cystitis


CLINICAL QUESTION
What is the efficacy of fosfomycin for uncomplicated cystitis in non-pregnant women?


BOTTOM LINE
At best, single dose fosfomycin has similar efficacy to other antibiotics for uncomplicated cystitis. However, the best quality, publicly funded trial showed it was not as efficacious as nitrofurantoin, with 58% of cases clinically resolving at 28 days compared to 70% for nitrofurantoin.



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EVIDENCE
Most recent systematic review1, 11 randomized controlled trials (RCTs), 1976 women, fosfomycin versus other antibiotics (examples norfloxacin, trimethoprim/sulfamethoxazole, nitrofurantoin) showed:
  • Clinical cure or improvement (non-complete symptom resolution): no difference.
  • Limitations: unreliable results (combined cure and failure rates together in the same analysis), most studies over 20 years old and industry sponsored.
  • Focusing on 4 heaviest weighted RCTs (make up >85% of outcomes in systematic review):
    • Most recent, highest quality, publicly funded, open-label RCT2of fosfomycin versus nitrofurantoin in 494 women. At 28 days:
      • Clinical resolution: 58% versus 70% nitrofurantoin, number needed to harm=8.
      • Adverse events: no difference.
    • Manufacturer-sponsored, double-blind RCT3 of fosfomycin versus nitrofurantoin in 231 women:
      • Cured or improved: no difference at Day 4, 9, or 42.
      • Stopped due to adverse events: 6% versus 0 nitrofurantoin (mainly gastrointestinal).
      • Limitations: unable to track all patient outcomes, study is 27 years old, not all randomized patients included in analysis.
        • “Worst-case” analysis accounting for missing data resulted in statistically fewer patients improving by Day 9: 84% versus 95% nitrofurantoin.
    • Manufacturer-sponsored double-blind RCT4 of fosfomycin versus nitrofurantoin in 521 women:
      • Cured: no difference up to 6 weeks after treatment.
      • Stopped due to adverse events: 2.6% versus 6.3% nitrofurantoin (not statistically different).
      • Limitations: not all randomized patients included in analysis, single author, study is 21 years old.
    • Second heaviest weighted RCT5: primary outcome was rectal cultures, not relevant.
Context:
  • Guidelines recommend nitrofurantoin, fosfomycin, or trimethoprim/sulfamethoxazole (if low risk of resistance) as empiric first-line treatment for uncomplicated cystitis in women.6,7
  • Fosfomycin is a single-dose, orange-flavoured, powder sachet for dissolution in cold water.8
  • Pricing: fosfomycin ~$30, nitrofurantoin ~$20 (5 days).9
  • No renal adjustments required for fosfomycin.8


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Author(s):

  • Adrienne J Lindblad BSP ACPR PharmD
  • Caitlin R Finley BHSc MSc
  • Christina Neil BScPharm
  • Emily Yu BScPharm
  • Kevin Kwok BScPharm

1. Cai T, Tamanini I, Tascini C, et al. J Urol. 2020 Mar; 203(3):570-578.

2. Huttner A, Kowalczyk A, Turjeman A, et al. JAMA. 2018 May 1; 319(17):1781-1789

3. Van Pienbroek E, Hermans J, Kaptein AA, et al. Pharm World Sci. 1993 Dec 17; 5(6):257-62.

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

5. Gupta K, Hooton TM, Stamm WE. J Antimicrob Chemother 2005; 56:243.

6. Gupta K, Hooton TM, Naber KG, et al. Clin Infect Dis. 2011 Mar 1; 52(5):e103-20.

7. Anger J, Lee, U, Ackerman L, et al. J Urol. 2019 Aug; 202:282-9.

8. Monurol [product monograph]. St-Laurent (QC): Paladin Labs Inc.; August 10, 2017. Available from: https://www.paladin-labs.com/our_products/Monurol-Sachet-PM-En.pdf Accessed Apr 27, 2020.

9. Price Comparison of Commonly Prescribed Pharmaceuticals in Alberta 2019. Alberta College of Family Physicians/PEER; March 6, 2019. Available from: https://acfp.ca/wp-content/uploads/2019/02/ACFPPricingDoc2019.pdf Accessed Apr 28, 2020.

Authors do not have any conflicts of interest to declare.