Curative Efficacy of Fosfomycin Tromethamine Versus Ciprofloxacin in the Initial Therapy of Uncomplicated UTI—a Prospective Open-Label Randomised Controlled Clinical Study

  • Iqbal SinghEmail author
  • Sheikh Mohd. Murtaza
  • Iqbal S. Kaur
  • Vivek Agrawal
Original Article


The precise current role of fosfomycin in the management of uncomplicated UTI (uUTI) is not well defined in the published English literature (PubMed()). We aim to compare the overall curative efficacy, safety, and outcome of fosfomycin tromethamine vis-a-vis Ciprofloxacin therapy in the initial management of uncomplicated UTI in a select group of patients. After obtaining prior institutional ethical clearance and written informed consent, 120 consenting patients with uUTI were selected as per protocol (based on symptoms of uUTI, positive urine culture sensitivity (c/s), urine routine/microscopy (r/m) or positive urine leukocyte esterase dipstick (LED) test) and enrolled in this study. They were randomized by computer draw of lots, into two groups of 60 each, randomised to receive initial empirical therapy with either fosfomycin (F-intervention arm) or Ciprofloxacin (C-comparator arm), pending the urine culture report. Patients were followed up with urine culture analysis and other parameters. The primary outcome measures were clinical/bacteriological response/resolution of UTI documented by negative urine culture (sent on day 3), absence of pyuria, and negative urine LED on 3rd day. Urine c/s was sent at day 0, but treatment was started (based on randomization) for those with urine r/m positive and positive LED test, pending the result of c/s. If the urine c/s turned out to be negative, the patient was excluded from the study. For the patients who satisfied the inclusion criteria, urine c/s was again sent on day 3, based on which report, bacteriological cure was defined. Secondary outcomes included bacteriological spectrum, antimicrobial sensitivity pattern, incidence of UTI caused by extended spectrum beta-lactamase (ESBL) producing strains of Escherichia coli, possible risk factors for UTI, side effects, ADRs, and ADEs of the drugs. E. coli and Klebsiella were the commonest cause of UTI while ESBL uropathogens were detected in 14/120 (11.67% 11 and 3 in F/C groups, respectively) patients. The sensitivity of uropathogens to F and C was 86 and 50% respectively while the overall clinical curative efficacy (CCE) of same was 83 and 43% respectively. In the subset of 14 patients with UTI due to ESBL, the CCE of F and C was 91 and 67% respectively. Side effects (minor and self-limiting) were significantly more common with the F group (p < 0.001), with diarrhoea being the commonest. Hospitalization was the commonest risk factor for UTI (27%) though the association of risk factors with UTI was not significantly different (p = 0.609). Fosfomycin was safe and significantly more efficacious in treating uncomplicated UTI (p < 0.001) versus ciprofloxacin. The overall incidence of UTI due to ESBL strains was 12% in which the CCE of fosfomycin was significantly higher (p = 0.023).


Fosfomycin Uncomplicated UTI Ciprofloxacin ESBL 


Funding Statement

The authors certify that the above study was conducted entirely from within regular running expenditure available to the Government Institution and no extra institutional financial grant or funding was availed of in any manner whatsoever.

Compliance with Ethical Standards

Ethical Statement

The authors declare that the above manuscript is in compliance with Ethical Standards for research in human participants and have no potential sources of conflict of interest associated with its publication.

Conflict of Interest

The authors declare that they have no conflict of interest.

Informed Consent Statement

The authors also certify that informed consent was obtained from all the human participants in this study. The study protocol was registered with the Clinical Trials Registry of India (CTRI) bearing number CTRI/2017/09/009922.


  1. 1.
    Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG et al (2011) International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 52(5):103–120Google Scholar
  2. 2.
    Popovic M, Steinort D, Pillai S, Joukhadar C (2010) Fosfomycin: an old, new friend? Eur J Clin Microbiol Infect Dis 29(2):127–142Google Scholar
  3. 3.
    Kahan FM, Kahan JS, Cassidy PJ, Kropp H The mechanism of action of fosfomycin (phosphonomycin). Ann N Y Acad Sci. 1974 May [cited 2017 Apr 12];235(1 Mode of Action):364–386. Available from:
  4. 4.
    Patel S, Balfour J, Bryson H (1997) Fosfomycin tromethamine. Drugs 53(4):637–656 Available from: Google Scholar
  5. 5.
    The Clinical and Laboratory Standards Institute (2016) M100S performance Standards for antimicrobial susceptibility testing. Clinical and Laboratory Standards Institute, WayneGoogle Scholar
  6. 6.
    Warren JW (2001) Practice guidelines for the treatment of uncomplicated cystitis. Curr Urol Rep:326–329Google Scholar
  7. 7.
    Randrianirina F, Soares JL, Carod JF, Ratsima E, Thonnier V, Combe P et al (2007) Antimicrobial resistance among uropathogens that cause community-acquired urinary tract infections in Antananarivo, Madagascar. J Antimicrob Chemother 59(2):309–312Google Scholar
  8. 8.
    Nabeth P, Perrier-Gros-Claude JD, Juergens-Behr A, Dromigny JA (2005) In vitro susceptibility of quinolone-resistant Enterobacteriaceae uropathogens to fosfomycin trometamol, in Dakar, Senegal. Scand J Infect Dis 37(6–7):497–499Google Scholar
  9. 9.
    Hatzaki D, Poulakou G, Katsarolis I, Lambri N, Souli M, Deliolanis I et al (2012) Cefditoren: comparative efficacy with other antimicrobials and risk factors for resistance in clinical isolates causing UTIs in outpatients. BMC Infect Dis 12(1):228 Available from: BMC Infectious DiseasesGoogle Scholar
  10. 10.
    Ceran N, Mert D, Kocdogan FY, Erdem I, Adalati R, Ozyurek S et al (2010) A randomized comparative study of single-dose fosfomycin and 5-day ciprofloxacin in female patients with uncomplicated lower urinary tract infections. J Infect Chemother 16(6):424–430Google Scholar
  11. 11.
    Muvunyi CM, Masaisa F, Bayingana C, Mutesa L, Musemakweri A, Muhirwa G et al (2011) Decreased susceptibility to commonly used antimicrobial agents in bacterial pathogens isolated from urinary tract infections in Rwanda: need for new antimicrobial guidelines. Am J Trop Med Hyg 84(6):923–928Google Scholar
  12. 12.
    Gupta K, Hooton TM, Stamm WE (2005) Isolation of fluoroquinolone-resistant rectal Escherichia coli after treatment of acute uncomplicated cystitis. J Antimicrob Chemother 56(1):243–246Google Scholar
  13. 13.
    Aguinaga A, Gil-Setas A, Mazón Ramos A, Alvaro A, García-Irure JJ, Navascues A (2018) Uncomplicated urinary tract infections. Antimicrobial susceptibility study in Navarre. [article in Spanish]. An Sist Sanit Navar 41(1):17–26. Google Scholar
  14. 14.
    Yang B, Yang F, Wang S, Wang Q, Liu Z, Feng W (2018) Analysis of the spectrum and antibiotic resistance of uropathogens in outpatients at a tertiary hospital. J Chemother 30(3):145–149. Google Scholar
  15. 15.
    Alamri A, Hamid ME, Abid M, Alwahhabi AM, Alqahtani KM, Alqarni MS (2018) Trend analysis of bacterial uropathogens and their susceptibility pattern: a 4-year (2013-2016) study from Aseer region, Saudi Arabia. Urol Ann 10(1):41–46. Google Scholar
  16. 16.
    Beierle I, Meibohm B, Derendorf H (1999) Gender differences in pharmacokinetics and pharmacodynamics. Int J Clin Pharmacol Ther 37(11):529–547Google Scholar
  17. 17.
    Schito GC (2003) Why fosfomycin trometamol as first line therapy for uncomplicated UTI? Int J Antimicrob Agents 22(SUPPL. 2):79–83Google Scholar
  18. 18.
    Sire JM, Nabeth P, Perrier-Gros-Claude JD, Bahsoun I, Siby T, Macondo EA, Gaye-Diallo A, Guyomard S, Seck A, Breurec S, Garin B (2007) Antimicrobial resistance in outpatient Escherichia coli urinary isolates in Dakar, Senegal. J Infect Dev Ctries 1(3):263–268Google Scholar
  19. 19.
    Bozkurt O, Kara CAS (2008) Comparison efficacy of single dose fosfomycin with ciprofloxacin in the treatment of urinary tract infection in symptomatic women. Turk Urol Derg 34:360–362Google Scholar
  20. 20.
    Arslan H, Azap OK, Ergonul O, Timurkaynak F (2005) Risk factors for ciprofloxacin resistance among Escherichia coli strains isolated from community-acquired urinary tract infections in Turkey. J Antimicrob Chemother 56(5):914–918Google Scholar
  21. 21.
    Akram M, Shahid M, Khan AU (2007) Etiology and antibiotic resistance patterns of community-acquired urinary tract infections in J N M C Hospital Aligarh, India. Ann Clin Microbiol Antimicrob 6(1):4 Available from: Google Scholar
  22. 22.
    Huttner A, Kowalczyk A, Turjeman A, Babich T, Brossier C, Eliakim-Raz N (2018) Effect of 5-day nitrofurantoin vs single-dose fosfomycin on clinical resolution of uncomplicated lower urinary tract infection in women: a randomized clinical trial. JAMA. 319(17):1781–1789. Google Scholar
  23. 23.
    Chervet D, Lortholary O, Zahar JR, Dufougeray A, Pilmis B, Partouche H (2018) Antimicrobial resistance in community-acquired urinary tract infections in Paris in 2015. Med Mal Infect 48(3):188–192. Google Scholar
  24. 24.
    Merino-Bohorquez V, Docobo-Pérez F, Sojo J, Morales I, Lupión C, Martín D (2018) Population pharmacokinetics and pharmacodynamics of fosfomycin in non-critically ill patients with bacteremic urinary infection caused by multidrug-resistant Escherichia coli. Clin Microbiol Infect.
  25. 25.
    Kranz J, Schmidt S, Lebert C, Schneidewind L, Mandraka F, Kunze M (2018) The 2017 update of the German clinical guideline on epidemiology, diagnostics, therapy, prevention, and management of uncomplicated urinary tract infections in adult patients. Part II: therapy and prevention. Urol Int 100(3):271–278. Google Scholar
  26. 26.
    Patel B, Patel K, Shetty A, Soman R, Rodrigues C (2017) Fosfomycin susceptibility in urinary tract Enterobacteriaceae. J Assoc Physicians India 65(9):14–16Google Scholar
  27. 27.
    Concia E, Bragantini D, Mazzaferri F (2017) Clinical evaluation of guidelines and therapeutic approaches in multi drug-resistant urinary tract infections. J Chemother 29(sup1):19–28. Google Scholar
  28. 28.
    Bahramian A, Eslami G, Hashemi A, Tabibi A, Heidary M (2018) Emergence of fosfomycin resistance among isolates of Escherichia coli harboring extended-spectrum and AmpC β-lactamases. Acta Microbiol Immunol Hung 65(1):15–25. Google Scholar
  29. 29.
    Martín-Gutiérrez G, Docobo-Pérez F, Rodriguez-Beltrán J, Rodríguez-Martínez JM, Aznar J, Pascual A, Blázquez J (2017) Urinary tract conditions affect fosfomycin activity against Escherichia coli strains harboring chromosomal mutations involved in fosfomycin uptake. Antimicrob Agents Chemother 62(1). Print 2018 Jan
  30. 30.
    Zykov IN, Samuelsen JL, Smabrekke L, Andersson DI, Sundsfjord A (2018) Pharmacokinetics and pharmacodynamics of fosfomycin and its activity against ESBL-, plasmid-mediated AmpC- and Carbapenemase-producing Escherichia coliin a murine urinary tract infection model. Antimicrob Agents Chemother 62.

Copyright information

© Association of Surgeons of India 2019

Authors and Affiliations

  1. 1.Department of Surgery (Urology)University College of Medical Sciences (University of Delhi) & GTB HospitalDelhi-95India
  2. 2.Department of SurgeryUniversity College of Medical Sciences (University of Delhi) & GTB HospitalDelhi-95India
  3. 3.Departmnet of MicrobiologyUniversity College of Medical Sciences (University of Delhi) & GTB HospitalDelhi-95India

Personalised recommendations