Journal of Antimicrobial Chemotherapy (1999) 43, 137-140
© 1999 The British Society for Antimicrobial Chemotherapy
Brief reports |
Fosfomycin tromethamine susceptibility of outpatient urine isolates of Escherichia coli and Enterococcus faecalisfrom ten North American medical centres by three methods
The Clinical Microbiology Institute, 9725 SW Commerce Circle Wilsonville, OR 97070, USA
Abstract
One hundred percent of 1097 Escherichia coli and 97.5% of 157 Enterococcus faecalis isolates from outpatient urine specimens at ten North American medical centres were susceptible to fosfomycin tromethamine. The Etest MICs correlated well with those of agar dilution. Disc diffusion zone diameters correlated well with MICs and supported the previously proposed zone diameter breakpoints for fosfomycin.
Introduction
Fosfomycin tromethamine is a phosphonic acid antibacterial agent that has been approved in the USA for the treatment of uncomplicated urinary tract infections due to Escherichia coli and Enterococcus faecalis. This agent, given as a single 3 g oral dose, has been reported to be comparable with other antimicrobials for the treatment of uncomplicated urinary tract infections in women.1,2,3,4 The present study was designed to assess the in-vitro activity of fosfomycin by three different test methods. Fosfomycin tromethamine and four other antimicrobial agents were tested against consecutive outpatient urinary tract isolates of E. coli and E. faecalis collected from ten geographically separate North American medical centres.
Materials and methods
Microorganisms
During the winter of 1998, approximately 110 consecutive outpatient urinary tract isolates of
E. coli were collected by each of ten medical centres (listed in Acknowledgements), and
were shipped frozen to the Clinical Microbiology Institute for testing. In addition, all urinary
isolates of enterococci encountered during this period were similarly collected and shipped. Only
organisms that were predominant and with colony counts 
104 cfu/mL were
included; mixed flora or isolates of questionable significance were excluded as were multiple
isolates from the same patient.
Antimicrobial agents
Fosfomycin tromethamine powder and fosfomycin Etest strips were provided by Forest Laboratories, New York, NY, USA. Ampicillin, ciprofloxacin, nitrofurantoin and trimethoprim/sulphamethoxazole were obtained from their respective manufacturers or from commercial sources. Commercially prepared antimicrobial discs included: fosfomycin, 200 µg + 50 µg of glucose 6-phosphate; ampicillin, 10 µg; ciprofloxacin, 5 µg; nitrofurantoin, 300 µg; and trimethoprim/sulphamethoxazole, 1.25/23.75 µg.
Susceptibility test
Fosfomycin MICs were determined by the agar dilution method as outlined by the National Committee for Clinical Laboratory Standards (NCCLS),5 using Mueller–Hinton agar supplemented with 25 mg/L of glucose 6-phosphate. Concentrations ranged from 0.06 to 128 mg of fosfomycin per litre (excluding the tromethamine portion of the salt). The inoculum contained approximately 1 x 104 cfu/spot and the results were read after 18–20 h incubation at 35°C in air. The other antimicrobials were tested by the broth microdilution method outlined by the NCCLS5 with concentrations of 0.03–64 mg/L (ampicillin), 0.015–8.0 mg/L (ciprofloxacin), 0.12–256 mg/L (nitrofurantoin), and 0.03/0.27–64/576 mg/L (trimethoprim/sulphamethoxazole). Disc diffusion tests were performed at the same time by the method outlined by the NCCLS.6 Fosfomycin Etest strips were also applied to the disc diffusion plates and read according to the instructions of the manufacturer. Etest MIC results that fell between even log2 dilution intervals were read as the next highest even log2 concentration.
Quality control
Quality control organisms were tested on each day of testing, and included: E. coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213 and ATCC 25923, and E. faecalis ATCC 29212. Of 368 tests with antibiotic/organism combinations that have NCCLS control limits, 98.6% of results fell within these limits. All quality control results with fosfomycin were within previously recommended ranges for this drug.7
Results and discussion
A total of 1097 urinary isolates of E. coli was tested and all (100%) were
susceptible to fosfomycin at 
64 mg/L (Table). The proportion
susceptible to the four
comparison drugs ranged from 67.7% (ampicillin) to 99.3% (ciprofloxacin). The
MIC90 of fosfomycin was 1.0 mg/L and >98% of the isolates were
susceptible to 2.0 mg/L of fosfomycin. Only minor differences in MIC distributions of all
five antimicrobials were observed among the ten participating medical centres.
|
During that sampling period, 180 urinary isolates of enterococci were collected: 157 were E. faecalis, 20 were E. faecium and three were other enterococcal species. The MICs of all five drugs were significantly higher for E. faecium than for E. faecalis. Though the fosfomycin MICs for enterococci were considerably higher than those for E. coli, 97.5% of E. faecalis and 95.6% of all enterococci were susceptible to fosfomycin at
64 mg/L. The percent susceptible to the other antimicrobials
ranged from 59.4% (ciprofloxacin) to 91.7% (nitrofurantoin) (Table). Eight
(4.4%) of the enterococcal isolates were resistant to vancomycin and five of those eight
strains were susceptible to fosfomycin. The comparison of fosfomycin MICs determined by agar dilution and by Etest is also shown inTable. The Etest MICs for E. coli averaged slightly more than half of one log 2 concentration higher than those determined by agar dilution, but 94% of the paired results were within one two-fold dilution of each other. For all enterococci, 99.5% of the paired MIC results by the two methods were within one two-fold dilution of each other with a slight skewing toward lower MICs by the Etest. The Etest appears to be an adequate substitute for agar dilution in determining MICs of fosfomycin tromethamine.
Scattergrams of the fosfomycin agar dilution MICs and the disc diffusion zone diameters are
provided in the Figure. No major or very major discrepancies occurred
with either organism; the minor discrepancy rates were 0.1% for E. coli and
2.5% for E. faecalis. The current susceptible breakpoint for fosfomycin is 64
mg/L, and this breakpoint has been shown to correlate well with clinical efficacy.8 The good correlation between MICs and disc diffusion zone
diameters plus the low discrepancy rates support the previously proposed zone diameter
breakpoints.9
|
In the USA fosfomycin tromethamine has not been widely used and, at the moment, virtually all E. coli isolates from outpatient urinary tract infections are susceptible to fosfomycin. This high susceptibility of E. coli to fosfomycin in the USA is unchanged from a previous survey.10 Since E. coliis by far the most prevalent outpatient urinary tract pathogen, fosfomycin appears to be a reasonable alternative for the empirical treatment of uncomplicated outpatient urinary tract infections.
Acknowledgments
The participating facilities and their respective microbiology director or supervisor were: The Cleveland Clinic, Cleveland, OH (J. Washington); Carolinas Medical Center, Charlotte, NC (S. Jenkins); Good Samaritan Hospital, Phoenix, AZ (M. Saubolle); St Vincent Medical Center, Portland, OR (M. Bauman); University of Alberta Hospital, Edmonton, Alberta, Canada (R. Rennie); UCLA Medical Center, Los Angeles, CA (J. Hindler); University of Iowa College of Medicine, Iowa City, IA (M. Pfaller); University of Massachusetts Medical Center, Worcester, MA (B. Brogden-Torres); University of New Mexico Medical Center, Albuquerque, NM (G. Overturf); and University of Rochester Medical Center, Rochester, NY (D. Hardy). Financial support was provided by Forest Laboratories, New York, NY.
Notes
* Corresponding author. Tel: +1-503-682-3232; Fax:
+1-503-682-2065; E-mail: cmi{at}hevanet.com 
References
1 . Crocchiolo, P. (1990). Single-dose fosfomycin trometamol versus multiple-dose cotrimoxazole in the treatment of lower urinary tract infections in general practice. Multicenter Group of General Practitioners. Chemotherapy 36, Suppl. 1 , 37–40.
2 . de Jong, Z., Pontonnier, F. & Plante, P. (1991). Single-dose fosfomycin trometamol (Monuril) versus multiple-dose norfloxacin: results of a multicenter study in females with uncomplicated lower urinary tract infections. Urology International 46, 344–8.[Web of Science][Medline]
3 . Neu, H. C. (1990). Fosfomycin trometamol versus amoxycillin—single-dose multicenter study of urinary tract infections. Chemotherapy 36, Suppl. 1, 19–23.
4 . Patel, S. S., Balfour, J. A. & Bryson, H. M. (1997). Fosfomycin tromethamine. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy as a single-dose oral treatment for acute uncomplicated lower urinary tract infections. Drugs 53 , 637–56.[Web of Science][Medline]
5 . National Committee for Clinical Laboratory Standards. (1997). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically— Fourth Edition: Approved Standard M7-A4 . NCCLS, Wayne, PA.
6 . National Committee for Clinical Laboratory Standards. (1997). Performance Standards for Antimicrobial Disk Susceptibility Tests— Sixth Edition: Approved Standard M2-A6 . NCCLS, Wayne, PA.
7 . Fuchs, P. C., Barry, A. L. & Brown, S. D. (1997). Susceptibility testing quality control studies with fosfomycin tromethamine. European Journal of Clinical Microbiology and Infectious Diseases16 , 538–40.[Web of Science][Medline]
8 . Naber, K. G. & Thyroff-Friesinger, U. (1992). Spectrum and susceptibility of pathogens causing acute uncomplicated lower UTI in females and its correlation to bacteriologic outcome after single dose therapy with fosfomycin trometamol versus ofloxacin/co-trimoxazole. Infection 20, Suppl. 4 , S296–301.
9 . Pfaller, M. A., Barry, A. L. & Fuchs, P. C. (1993). Evaluation of disk susceptibility testing of fosfomycin tromethamine. Diagnostic Microbiology and Infectious Disease17 , 67–70.[Web of Science][Medline]
10
.
Barry, A. L. & Brown, S. D. (1995).
Antibacterial spectrum of fosfomycin trometamol. Journal of Antimicrobial
Chemotherapy 35, 228–30.
Received 20 April 1998; returned 17 June 1998; revised 6 July 1998; accepted 3 August 1998
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. J. Knottnerus, S. Nys, G. ter Riet, G. Donker, S. E. Geerlings, and E. Stobberingh Fosfomycin tromethamine as second agent for the treatment of acute, uncomplicated urinary tract infections in adult female patients in The Netherlands? J. Antimicrob. Chemother., August 1, 2008; 62(2): 356 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. de Cueto, L. Lopez, J. R. Hernandez, C. Morillo, and A. Pascual In Vitro Activity of Fosfomycin against Extended-Spectrum-{beta}-Lactamase- Producing Escherichia coli and Klebsiella pneumoniae: Comparison of Susceptibility Testing Procedures Antimicrob. Agents Chemother., January 1, 2006; 50(1): 368 - 370. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||