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  Table of Contents  
Year : 2015  |  Volume : 33  |  Issue : 4  |  Page : 611-612

Technical and interpretative issues of fosfomycin susceptibility testing

Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India

Date of Submission11-Jul-2014
Date of Acceptance12-Jan-2015
Date of Web Publication16-Oct-2015

Correspondence Address:
V Balaji
Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0255-0857.167338

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How to cite this article:
Chitra C, Kumar D, Shakti L, Diana S R, Balaji V. Technical and interpretative issues of fosfomycin susceptibility testing. Indian J Med Microbiol 2015;33:611-2

How to cite this URL:
Chitra C, Kumar D, Shakti L, Diana S R, Balaji V. Technical and interpretative issues of fosfomycin susceptibility testing. Indian J Med Microbiol [serial online] 2015 [cited 2020 Aug 9];33:611-2. Available from:

Dear Editor,

Emergence of drug-resistant organisms have necessitated treatment with old antibiotics of renewed interest like fosfomycin. Fosfomycin is a unique antimicrobial agent, sharing no structural similarity and lacks cross-resistance with other antimicrobial agents.[1] The Infectious Disease Society of America (IDSA) and European Society for Microbiology and Infectious Diseases (ESMID) recommends fosfomycin as one of the first-line choice of therapy for uncomplicated cystitis and pyelonephritis.[2] The systemic use of fosfomycin for treatment of invasive infection by drug-resistant organism is being contemplated due to lack of effective alternative antibiotics. While, urinary isolates showed good susceptibility among ESBL producing E. coli,[3] the activity of this drug against carbapenem-resistant isolates needs to be studied. The aim of this study is to determine the activity of fosfomycin against carbapenem-resistant isolates recovered from blood, urine and other sterile body fluid samples in a tertiary care centre.

A total of 200 carbapenem resistant (CR) Klebsiella sp. (n = 70), CR-E. coli (n = 61), CR-Pseudomonas aeruginosa (n = 32) and CR-Acinetobacter baumannii calcoaceticus complex (Abcc) (n = 37) using Clinical and Laboratory Standards Institute (CLSI) guideline [4] from blood, urine and other sterile body fluid samples were randomly selected from January 2013 to April 2014. Minimum inhibitory concentration (MIC) for fosfomycin was determined using e-test strips incorporated with Glucose-6-phosphate (Biomerieux, Marcy-l' Etoile, France) on Mueller Hinton agar (BD, Sparks, MD). Controls ATCC 25922 E. coli and ATCC 27853 P. aeruginosa were satisfactory. This study was approved by the institutional review board of Christian Medical College, Vellore (IRB Min. No 8691 dated 26.02.2014).

All isolates were extensively drug-resistant. Colistin was the most active agent against the isolates with only two isolates of E. coli being resistant to colistin. [Table 1] gives the interpretation of the MIC using CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria and the MIC50 and MIC90. There is significant difference in the level of susceptibility for Klebsiella sp. using different criteria (P = 0.0012), whereas for the other organisms, there was no difference in the categorization (P = 0.99–1). This study revealed high susceptibility of CR-E. coli to fosfomycin (95.1%) similar to observation made by Livermore et al. and Kaase et al.[5],[6] CR-Klebsiella showed lower level of susceptibility (35.7%) following the EUCAST criteria. However, applying the E. coli CLSI breakpoint, susceptibility of Klebsiella sp. is significantly raised to 64.2%. Perdigao-Neto et al. similarly reported that the same isolates tested by e-test showed 85% and 48% susceptibility by CLSI and EUCAST, respectively.[7] The level of resistance in this study CR-strains is higher than those observed in Germany, Brazil and Greece.[5],[7],[8] Interestingly, Klebsiella isolates from blood and sterile body fluid showed increased resistance compared to urine isolates, while E. coli isolates were uniformly susceptible to both blood/body fluids and urine isolates; however, the MIC90 was two-fold higher among blood and other fluids isolates compared to urinary isolates. This observation needs to be further investigated for its potential implication for systemic therapy for invasive infections as well as breakpoint determination for systemic and urinary tract infections. Studies comparing e-test and disc diffusion with the reference agar dilution assay have demonstrated minor errors to unacceptable major and very major errors with both methods.[5],[7] Disc diffusion breakpoints are available for CLSI, but no interpretive breakpoint is reported in EUCAST. There is a need for optimization of disc diffusion or e-test which are simple to execute and applicable for single isolate testing.
Table 1: Interpretation of fosfomycin MIC by CLSI and EUCAST criteria

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We would like to thank Cipla educational grant for funding the study. (IRB Min. No 8691 dated 26.02.2014).

Financial support and sponsorship

This study was funded by Cipla Educational grant. The funding agency had no role in planning, executing and interpretation of results of the study.

Conflicts of interest

There are no conflicts of interest.

 ~ References Top

Michalopoulos AS, Livaditis IG, Gougoutas V. The revival of fosfomycin. Int J Infect Dis 2011;15:e732-9.  Back to cited text no. 1
Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, et al. Infectious Diseases Society of America, European Society for Microbiology and Infectious Diseases. 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 2011;52:e103-20.  Back to cited text no. 2
Sahni RD, Balaji V, Varghese R, John J, Tansarli GS, Falagas ME. Evaluation of fosfomycin activity against uropathogens in a fosfomycin-naive population in South India: A prospective study. Future Microbiol 2013;8:675-80.  Back to cited text no. 3
Clinical and Laboratory Standards Institute. Performance standards for anti-microbial susceptibility testing; twenty-second informational supplement. Document M100-S22. Wayne, PA: CLSI; 2013.  Back to cited text no. 4
Kaase M, Szabados F, Anders A, Gatermann SG. Fosfomycin susceptibility in carbapenem-resistant enterobacteriaceae from Germany. J Clin Microbiol 2014;52:1893-7.  Back to cited text no. 5
Livermore DM, Warner M, Mushtaq S, Doumith M, Zhang J, Woodford N. What remains against carbapenem-resistant Enterobacteriaceae? Evaluation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline. Int J Antimicrob Agents 2011;37:415-9.  Back to cited text no. 6
Perdigao-Neto LV, Oliveira MS, Rizek CF, Carrilho CM, Costa SF, Levin AS. Susceptibility of multiresistant gram-negative bacteria to fosfomycin and performance of different susceptibility testing methods. Antimicrob Agents Chemother 2014;58:1763-7.  Back to cited text no. 7
Falagas ME, Kanellopoulou MD, Karageorgopoulos DE, Dimopoulos G, Rafailidis PI, Skarmoutsou ND, et al. Antimicrobial susceptibility of multidrug-resistant Gram negative bacteria to fosfomycin. Eur J Clin Microbiol Infect Dis 2008;27:439-43.  Back to cited text no. 8


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