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Published in: International Urology and Nephrology 9/2017

01-09-2017 | Nephrology - Original Paper

Fosfomycin for the treatment of drug-resistant urinary tract infections: potential of an old drug not explored fully

Authors: Vrushali Patwardhan, Sarman Singh

Published in: International Urology and Nephrology | Issue 9/2017

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Abstract

Introduction

Increased emergence of bacterial resistance and the limited options of novel antimicrobial agents have necessitated the reintroduction of some old antimicrobial agents. One such drug is fosfomycin, but its potential has not been explored fully, especially in India.

Aims and objectives

To analyze the in vitro activity of fosfomycin, against the urinary isolates and to compare it with in vitro activity of other orally administered antimicrobial agents.

Materials and methods

This was a prospective observational study conducted between July 2014 and June 2016. All consecutive, non-duplicate and clinically significant urinary isolates obtained from patients of all ages and both genders, diagnosed to have UTI, were included. Patients already on antibiotic therapy were excluded. Urine culture was performed by semiquantitative method on cysteine lactose electrolyte-deficient medium and the isolates obtained in significant count were subjected to antimicrobial sensitivity testing by the Kirby Bauer disk diffusion method as per CLSI guidelines.

Results

A total of 3947 non-repeating urinary isolates were included in the study, of which 2684 (68%) isolates originated from adult outpatients and remaining 1236 (32%) isolates from pediatric patients. Of these 2783 isolates were from enterobacteriaceae family. Out of these 2730 (98.1%) were sensitive to fosfomycin. Most [375 of 385 (97.4%)] Pseudomonas spp were also susceptible to fosfomycin. A majority of ESBL- (96.5%) and MBL (91.9%)-producing isolates were also susceptible to fosfomycin and so were of Gram-positive isolates [698/707 (96%)] and MRSA [61/69 (88.4%)] were susceptible to fosfomycin.

Conclusions

Fosfomycin showed an excellent in vitro activity against all urinary pathogens, including the Gram-positive or Gram-negative, ESBL and MBL producers. Fosfomycin should be considered as a highly effective alternative in treatment UTIs in both adults and pediatric patients.
Literature
1.
go back to reference Hooton TM (2012) Clinical practice uncomplicated urinary tract infection. N Engl J Med 366:1028–1037CrossRefPubMed Hooton TM (2012) Clinical practice uncomplicated urinary tract infection. N Engl J Med 366:1028–1037CrossRefPubMed
3.
go back to reference Qiao LD, Zheng B, Chen S et al (2013) Evaluation of three-dose fosfomycin tromethamine in the treatment of patients with urinary tract infections: an uncontrolled, open-label, multicentre study. BMJ Open. doi:10.1136/bmjopen-2013-004157 Qiao LD, Zheng B, Chen S et al (2013) Evaluation of three-dose fosfomycin tromethamine in the treatment of patients with urinary tract infections: an uncontrolled, open-label, multicentre study. BMJ Open. doi:10.​1136/​bmjopen-2013-004157
4.
go back to reference Auer S, Wojna A, Hell M (2010) Oral treatment options for ambulatory patients with urinary tract infections caused by extended-spectrum-beta-lactamase-producing Escherichia coli. Antimicrob Agents Chemother 54(9):4006–4008CrossRefPubMedPubMedCentral Auer S, Wojna A, Hell M (2010) Oral treatment options for ambulatory patients with urinary tract infections caused by extended-spectrum-beta-lactamase-producing Escherichia coli. Antimicrob Agents Chemother 54(9):4006–4008CrossRefPubMedPubMedCentral
5.
go back to reference Falagas ME, Polemis M, Alexiou VG et al (2008) Antimicrobial resistance of Esherichia coli urinary isolates from primary care patients in Greece. Med Sci Mon 14(2):CR75–79 Falagas ME, Polemis M, Alexiou VG et al (2008) Antimicrobial resistance of Esherichia coli urinary isolates from primary care patients in Greece. Med Sci Mon 14(2):CR75–79
6.
go back to reference Boucher HW, Talbot GH, Benjamin DKJ et al (2013) Infectious Diseases Society of America. 10 × ’20 Progress development of new drugs active against Gram-negative bacilli: an update from the Infectious Diseases Society of America. Clin Infect Dis 56:1685–1694CrossRefPubMedPubMedCentral Boucher HW, Talbot GH, Benjamin DKJ et al (2013) Infectious Diseases Society of America. 10 × ’20 Progress development of new drugs active against Gram-negative bacilli: an update from the Infectious Diseases Society of America. Clin Infect Dis 56:1685–1694CrossRefPubMedPubMedCentral
7.
go back to reference Garau J (2008) Other antimicrobials of interest in the era of extended-spectrum b-lactamases: fosfomycin, nitrofurantoin and tigecycline. Clin Microbiol Infect 14(1):198–202CrossRefPubMed Garau J (2008) Other antimicrobials of interest in the era of extended-spectrum b-lactamases: fosfomycin, nitrofurantoin and tigecycline. Clin Microbiol Infect 14(1):198–202CrossRefPubMed
8.
go back to reference Magiorakos AP, Srinivasan A, Carey RB et al (2012) Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18:268–281CrossRefPubMed Magiorakos AP, Srinivasan A, Carey RB et al (2012) Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18:268–281CrossRefPubMed
10.
11.
go back to reference Cueto M, Lopez L, Hernandez JR et al (2006) In vitro activity of fosfomycin against extended-spectrum-lactamase-producing Escherichia coli and Klebsiella pneumoniae: comparison of susceptibility testing procedures. Antimicrob Agents Chemother 50:368–370CrossRefPubMedPubMedCentral Cueto M, Lopez L, Hernandez JR et al (2006) In vitro activity of fosfomycin against extended-spectrum-lactamase-producing Escherichia coli and Klebsiella pneumoniae: comparison of susceptibility testing procedures. Antimicrob Agents Chemother 50:368–370CrossRefPubMedPubMedCentral
12.
go back to reference Endimiani A, Patel G, Hujer KM et al (2010) In vitro activity of fosfomycin against bla KPC-containing Klebsiella pneumoniae isolates, including those nonsusceptible to tigecycline and/or colistin. Antimicrob Agents Chemother 54(1):526–529CrossRefPubMed Endimiani A, Patel G, Hujer KM et al (2010) In vitro activity of fosfomycin against bla KPC-containing Klebsiella pneumoniae isolates, including those nonsusceptible to tigecycline and/or colistin. Antimicrob Agents Chemother 54(1):526–529CrossRefPubMed
13.
go back to reference Neuner EA, Sekeres J, Hall GS et al (2012) Experience with fosfomycin for treatment of urinary tract infections due to multidrug-resistant organisms. Antimicrob Agents Chemother 56(11):5744–5748CrossRefPubMedPubMedCentral Neuner EA, Sekeres J, Hall GS et al (2012) Experience with fosfomycin for treatment of urinary tract infections due to multidrug-resistant organisms. Antimicrob Agents Chemother 56(11):5744–5748CrossRefPubMedPubMedCentral
14.
go back to reference Rosso-Fernández C, Sojo-Dorado J, Barriga A et al (2015) Fosfomycin versus meropenem in bacteraemic urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli (FOREST): study protocol for an investigator-driven randomised controlled trial. BMJ Open. doi:10.1136/bmjopen-2014-007363 PubMedPubMedCentral Rosso-Fernández C, Sojo-Dorado J, Barriga A et al (2015) Fosfomycin versus meropenem in bacteraemic urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli (FOREST): study protocol for an investigator-driven randomised controlled trial. BMJ Open. doi:10.​1136/​bmjopen-2014-007363 PubMedPubMedCentral
15.
go back to reference Lai B, Zheng B, Li Y, et al (2014) In vitro susceptibility of Escherichia coli strains isolated from urine samples obtained in mainland China to fosfomycin trometamol and other antibiotics: a 9-year surveillance study (2004–2012). BMC Infect Dis. doi:10.1186/1471-2334-14-66 Lai B, Zheng B, Li Y, et al (2014) In vitro susceptibility of Escherichia coli strains isolated from urine samples obtained in mainland China to fosfomycin trometamol and other antibiotics: a 9-year surveillance study (2004–2012). BMC Infect Dis. doi:10.​1186/​1471-2334-14-66
16.
go back to reference Lu PL, Liu YC, Toh HS et al (2012) Epidemiology and antimicrobial susceptibility profiles of Gram-negative bacteria causing urinary tract infections in the Asia-Pacific region: 2009–2010 results from the study for monitoring antimicrobial resistance trends (SMART). Int J Antimicrob Agents 40(Suppl):S37–S43CrossRefPubMed Lu PL, Liu YC, Toh HS et al (2012) Epidemiology and antimicrobial susceptibility profiles of Gram-negative bacteria causing urinary tract infections in the Asia-Pacific region: 2009–2010 results from the study for monitoring antimicrobial resistance trends (SMART). Int J Antimicrob Agents 40(Suppl):S37–S43CrossRefPubMed
17.
go back to reference Liu HY, Lin HC, Lin YC et al (2011) Antimicrobial susceptibilities of urinary extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae to fosfomycin and nitrofurantoin in a teaching hospital in Taiwan. J Microbiol Immunol Infect 44(5):364–368CrossRefPubMed Liu HY, Lin HC, Lin YC et al (2011) Antimicrobial susceptibilities of urinary extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae to fosfomycin and nitrofurantoin in a teaching hospital in Taiwan. J Microbiol Immunol Infect 44(5):364–368CrossRefPubMed
18.
go back to reference Cho YH, Jung SJ, Chung HS et al (2015) Antimicrobial susceptibilities of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in health care-associated urinary tract infection: focus on susceptibility to fosfomycin. Int Urol Nephrol 47:1059–1066CrossRefPubMed Cho YH, Jung SJ, Chung HS et al (2015) Antimicrobial susceptibilities of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in health care-associated urinary tract infection: focus on susceptibility to fosfomycin. Int Urol Nephrol 47:1059–1066CrossRefPubMed
19.
go back to reference de Cueto M, Hernandez JR, Lopez-Cerero L et al (2006) Activity of fosfomycin against extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae. Enferm Infecc Microbiol Clin 24:613–616CrossRefPubMed de Cueto M, Hernandez JR, Lopez-Cerero L et al (2006) Activity of fosfomycin against extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae. Enferm Infecc Microbiol Clin 24:613–616CrossRefPubMed
20.
go back to reference Falagas ME, Kastoris AC, Kapaskelis AM, Karageorgopoulos DE (2010) Fosfomycin for the treatment of multidrug-resistant, including extendedspectrum beta-lactamase producing, Enterobacteriaceae infections: a systematic review. Lancet Infect Dis. doi:10.1016/S1473-3099(09)70325-1 PubMed Falagas ME, Kastoris AC, Kapaskelis AM, Karageorgopoulos DE (2010) Fosfomycin for the treatment of multidrug-resistant, including extendedspectrum beta-lactamase producing, Enterobacteriaceae infections: a systematic review. Lancet Infect Dis. doi:10.​1016/​S1473-3099(09)70325-1 PubMed
21.
go back to reference Senol S, Tasbakan M, Pullukcu H et al (2010) Carbapenem versus fosfomycin tromethanol in the treatment of extended-spectrum beta-lactamase-producing Escherichia coli-related complicated lower urinary tract infection. J Chemother 22:355–357CrossRefPubMed Senol S, Tasbakan M, Pullukcu H et al (2010) Carbapenem versus fosfomycin tromethanol in the treatment of extended-spectrum beta-lactamase-producing Escherichia coli-related complicated lower urinary tract infection. J Chemother 22:355–357CrossRefPubMed
22.
go back to reference Sabharwal ER, Sharma R (2015) Fosfomycin: an alternative therapy for the treatment of UTI amidst escalating antimicrobial resistance. J Clin Diagn Res 9(12):06–09 Sabharwal ER, Sharma R (2015) Fosfomycin: an alternative therapy for the treatment of UTI amidst escalating antimicrobial resistance. J Clin Diagn Res 9(12):06–09
23.
go back to reference Linsenmeyer K, Strymish J, Weir S et al (2015) Activity of fosfomycin against extended-spectrum-β-lactamase-producing uropathogens in patients in the community and hospitalized patients. Antimicrob Agents Chemother. doi:10.1128/AAC.02614-15 PubMedCentral Linsenmeyer K, Strymish J, Weir S et al (2015) Activity of fosfomycin against extended-spectrum-β-lactamase-producing uropathogens in patients in the community and hospitalized patients. Antimicrob Agents Chemother. doi:10.​1128/​AAC.​02614-15 PubMedCentral
24.
go back to reference Karlowsky JA, Denisuik AJ, Lagacé-Wiens PRS et al (2014) In vitro activity of fosfomycin against Escherichia coli isolated from patients with urinary tract infections in Canada as part of the CANWARD surveillance study. Antimicrob Agents Chemother 58(2):1252–1256CrossRefPubMedPubMedCentral Karlowsky JA, Denisuik AJ, Lagacé-Wiens PRS et al (2014) In vitro activity of fosfomycin against Escherichia coli isolated from patients with urinary tract infections in Canada as part of the CANWARD surveillance study. Antimicrob Agents Chemother 58(2):1252–1256CrossRefPubMedPubMedCentral
25.
go back to reference Grabein B, Graninger W, Rodríguez J, et al (2016) Intravenous fosfomycin back to the future. Systematic review and meta-analysis of the clinical literature. Clin Microbiol Infect. doi:10.1016/j.cmi.2016.12.005 Grabein B, Graninger W, Rodríguez J, et al (2016) Intravenous fosfomycin back to the future. Systematic review and meta-analysis of the clinical literature. Clin Microbiol Infect. doi:10.​1016/​j.​cmi.​2016.​12.​005
27.
go back to reference Sahni RD, Balaji V, Varghese R et al (2013) Evaluation of fosfomycin activity against uropathogens in a fosfomycin-naive population in South India: a prospective study. Future Microbiol 8(5):675–680CrossRefPubMed Sahni RD, Balaji V, Varghese R et al (2013) Evaluation of fosfomycin activity against uropathogens in a fosfomycin-naive population in South India: a prospective study. Future Microbiol 8(5):675–680CrossRefPubMed
Metadata
Title
Fosfomycin for the treatment of drug-resistant urinary tract infections: potential of an old drug not explored fully
Authors
Vrushali Patwardhan
Sarman Singh
Publication date
01-09-2017
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 9/2017
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-017-1627-6

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