ANTIMICROBIAL AGENTS
AND
CHEMOTHERAPY, June 1991,
p.
Vol. 35, No. 6
1235-1238
0066-4804/91/061235-04$02.00/0 Copyright © 1991, American Society for Microbiology
In Vitro Susceptibility Testing Procedures for Fosfomycin Tromethamine ARTHUR L.
BARRY'*
AND
PETER C. FUCHS2
The Clinical Microbiology Institute, P.O. Box 947, Tualatin, Oregon 97062,1 and St. Vincent Hospital and Medical Center, Portland, Oregon 972252 Received 31 December 1990/Accepted 20 March 1991
Fosfomycin tromethamine (previously fosfomycin trometamol) is an orally administered fosfomycin which be used for single-dose therapy of uncomplicated urinary tract infections. Fosfomycin tromethamine, norfloxacin, and trimethoprim-sulfamethoxazole inhibited >90% of 352 bacterial isolates representing 25 different species; trimethoprim and nalidixic acid had narrower spectrums of activity. Strains of Escherichia, Citrobacter, Enterobacter, and Klebsiella species were much more susceptible when glucose-6-phosphate was added to the test medium, but isolates belonging to other genera were not affected. may
the validity of those tentative breakpoints for fosfomycin tromethamine tested by National Committee for Clinical Laboratory Standards approved methods are currently under way in the United States (9). A breakpoint of 256 >512 32 64 64 128 128
256 512 16 32 32 32 64 16 16 8.0 16 16 16 32
>256 >512 32 128 128 256 256
4.0 2.0 4.0 4.0 4.0
64 64 16 32 16 32 64 128 128 256 64 128
256 256 128 256 256 256 256
>256 >512 >256 512 >512 >512 >512
16 32 16 16 32 32 32
128 256 128 128 128 128 128
128 64 128 64 64 64 64
512 256 256 256 256 256 256
Range
16->256
1.0-512
c0.5-32 512 51.0->512 s1.0->512 .1.0->512
64->256 32->512 32->256 32->512 64->512 32->512 32->512
2.0-128
1l.0-512 2.0-256 51.0-512
s1.0-512 .1.0-256 51.0-512
512 50.5-512 .1.0->512 51.0->512 .1.0->512 51.0->512 Continued on following page
1238
ANTIMICROB. AGENTS CHEMOTHER.
NOTES TABLE 2-Continued
MIC (14/fl)b
Mueller-Hinton medium
G-6P added
(.g/ml)
50'%o
90o
Agar Broth Agar Broth Broth Broth Broth
0 0 25 25 50 100 200
128 128 128 128 128 128
128 128 128 128 128 128 256
Enterococcus species (41)
Agar Broth Agar Broth Broth Broth Broth
0 0 25 25 50 100 200
32 32 32 32 32 32 32
64 64 64 64 64 64 64
16->256 16-512 16->256 16->512 16-512 16-512 16-512
Staphylococcus saprophyticus (30)
Agar Broth Agar Broth Broth Broth Broth
0 0 25 25 50 100 200
128 64 128 64 64 64 64
>256 256 512 512 512 256 256
64->256 16->512 64->256 16->512 16->512 16->512 16->512
Microorganism (no. tested)a
Acinetobacter calcoaceticus subsp. anitratus (10)
128
Range
64-256 64-256 64-128 64-512 64-128 64-256 64-256
a The species are listed in Table 1. b MICs are expressed as the concentration of active fosfomycin in fosfomycin tromethamine. MICs for 50 and 90o of the isolates tested are displayed along with the range (minimum to maximum) of MICs. c Proteus species were not tested by the agar dilution method.
after oral administration; fosfomycin tromethamine deserved further consideration for single-dose treatment of urinary tract infections. REFERENCES 1. Andrews, J. M., F. Baguero, J. M. Beltran, E. Canton, F. Crokaert, M. Gobernado, R. Gomez-Ius, E. Loza, M. Navarro, T. Olay, A. Rodriguez, M. V. Vicente, R. Wise, and E. Yourassowky. 1983. International collaborative study on standardization of bacterial sensitivity to fosfomycin. J. Antimicrob. Chemother. 12:357-361. 2. Bella, D. D., and V. Ferrari. 1988. Monuril: historical background, p. 116-120. In H. C. Neu and J. D. Williams (ed.), New trend in urinary tract infections: the single-dose therapy. S. Karger AG, Basel. 3. Bergan, T., G. Mastropaolo, F. DiMario, and R. Naccarato. 1988. Pharmacokinetics of fosfomycin and influence of cimetidime and metoclopramide on the bioavailability of fosfomycin trometamol, p. 157-166. In H. C. Neu and J. D. Williams (ed.), New trend in urinary tract infections: the single-dose therapy. S. Karger AG, Basel. 4. Borsa, F., A. Leroy, J.-P. Fillastre, M. Godin, and B. Moulin. 1988. Comparative pharmacokinetics of tromethamine fosfomycin and calcium fosfomycin in young and elderly adults. Anti-
microb. Agents Chemother. 32:938-941. 5. Greenwood, D., A. Jones, and A. Eley. 1986. Factors influencing the activity of the trometamol salt of fosfomycin. Eur. J. Clin. Microbiol. 5:29-34. 6. Kahan, F. M., J. S. Kahan, P. J. Cassidy, and H. Kropp. 1974. The mechanism of action of fosfomycin (phosphomycin). Ann. N.Y. Acad. Sci. 235:364-386. 7. Lerner, S. A., S. Price, and S. Kulkarni. 1988. Microbiological studies of fosfomycin trometamol against urinary isolates in vitro, p. 121-128. In H. C. Neu and J. D. Williams (ed.), New trend in urinary tract infections: the single-dose therapy. S. Karger AG, Basel. 8. LiPira, G., C. Pruzzo, and G. C. Schito. 1987. Monuril and modification of pathogenicity traits in resistant microorganisms. Eur. Urol. 13(Suppl. 1):92-97. 9. National Comnmittee for Clinical Laboratory Standards. 1990. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A2, 2nd ed.
National Committee for Clinical Laboratory Standards, Villanova, Pa. 10. Wise, R., and J. M. Andrews. 1988. Fosfomycin trometamol: an in vitro study, p. 232-241. In H. C. Neu and J. D. Williams (ed.), New trend in urinary tract infections: the single-dose therapy. S. Karger AG, Basel.
AND
CHEMOTHERAPY, June 1991,
p.
Vol. 35, No. 6
1235-1238
0066-4804/91/061235-04$02.00/0 Copyright © 1991, American Society for Microbiology
In Vitro Susceptibility Testing Procedures for Fosfomycin Tromethamine ARTHUR L.
BARRY'*
AND
PETER C. FUCHS2
The Clinical Microbiology Institute, P.O. Box 947, Tualatin, Oregon 97062,1 and St. Vincent Hospital and Medical Center, Portland, Oregon 972252 Received 31 December 1990/Accepted 20 March 1991
Fosfomycin tromethamine (previously fosfomycin trometamol) is an orally administered fosfomycin which be used for single-dose therapy of uncomplicated urinary tract infections. Fosfomycin tromethamine, norfloxacin, and trimethoprim-sulfamethoxazole inhibited >90% of 352 bacterial isolates representing 25 different species; trimethoprim and nalidixic acid had narrower spectrums of activity. Strains of Escherichia, Citrobacter, Enterobacter, and Klebsiella species were much more susceptible when glucose-6-phosphate was added to the test medium, but isolates belonging to other genera were not affected. may
the validity of those tentative breakpoints for fosfomycin tromethamine tested by National Committee for Clinical Laboratory Standards approved methods are currently under way in the United States (9). A breakpoint of 256 >512 32 64 64 128 128
256 512 16 32 32 32 64 16 16 8.0 16 16 16 32
>256 >512 32 128 128 256 256
4.0 2.0 4.0 4.0 4.0
64 64 16 32 16 32 64 128 128 256 64 128
256 256 128 256 256 256 256
>256 >512 >256 512 >512 >512 >512
16 32 16 16 32 32 32
128 256 128 128 128 128 128
128 64 128 64 64 64 64
512 256 256 256 256 256 256
Range
16->256
1.0-512
c0.5-32 512 51.0->512 s1.0->512 .1.0->512
64->256 32->512 32->256 32->512 64->512 32->512 32->512
2.0-128
1l.0-512 2.0-256 51.0-512
s1.0-512 .1.0-256 51.0-512
512 50.5-512 .1.0->512 51.0->512 .1.0->512 51.0->512 Continued on following page
1238
ANTIMICROB. AGENTS CHEMOTHER.
NOTES TABLE 2-Continued
MIC (14/fl)b
Mueller-Hinton medium
G-6P added
(.g/ml)
50'%o
90o
Agar Broth Agar Broth Broth Broth Broth
0 0 25 25 50 100 200
128 128 128 128 128 128
128 128 128 128 128 128 256
Enterococcus species (41)
Agar Broth Agar Broth Broth Broth Broth
0 0 25 25 50 100 200
32 32 32 32 32 32 32
64 64 64 64 64 64 64
16->256 16-512 16->256 16->512 16-512 16-512 16-512
Staphylococcus saprophyticus (30)
Agar Broth Agar Broth Broth Broth Broth
0 0 25 25 50 100 200
128 64 128 64 64 64 64
>256 256 512 512 512 256 256
64->256 16->512 64->256 16->512 16->512 16->512 16->512
Microorganism (no. tested)a
Acinetobacter calcoaceticus subsp. anitratus (10)
128
Range
64-256 64-256 64-128 64-512 64-128 64-256 64-256
a The species are listed in Table 1. b MICs are expressed as the concentration of active fosfomycin in fosfomycin tromethamine. MICs for 50 and 90o of the isolates tested are displayed along with the range (minimum to maximum) of MICs. c Proteus species were not tested by the agar dilution method.
after oral administration; fosfomycin tromethamine deserved further consideration for single-dose treatment of urinary tract infections. REFERENCES 1. Andrews, J. M., F. Baguero, J. M. Beltran, E. Canton, F. Crokaert, M. Gobernado, R. Gomez-Ius, E. Loza, M. Navarro, T. Olay, A. Rodriguez, M. V. Vicente, R. Wise, and E. Yourassowky. 1983. International collaborative study on standardization of bacterial sensitivity to fosfomycin. J. Antimicrob. Chemother. 12:357-361. 2. Bella, D. D., and V. Ferrari. 1988. Monuril: historical background, p. 116-120. In H. C. Neu and J. D. Williams (ed.), New trend in urinary tract infections: the single-dose therapy. S. Karger AG, Basel. 3. Bergan, T., G. Mastropaolo, F. DiMario, and R. Naccarato. 1988. Pharmacokinetics of fosfomycin and influence of cimetidime and metoclopramide on the bioavailability of fosfomycin trometamol, p. 157-166. In H. C. Neu and J. D. Williams (ed.), New trend in urinary tract infections: the single-dose therapy. S. Karger AG, Basel. 4. Borsa, F., A. Leroy, J.-P. Fillastre, M. Godin, and B. Moulin. 1988. Comparative pharmacokinetics of tromethamine fosfomycin and calcium fosfomycin in young and elderly adults. Anti-
microb. Agents Chemother. 32:938-941. 5. Greenwood, D., A. Jones, and A. Eley. 1986. Factors influencing the activity of the trometamol salt of fosfomycin. Eur. J. Clin. Microbiol. 5:29-34. 6. Kahan, F. M., J. S. Kahan, P. J. Cassidy, and H. Kropp. 1974. The mechanism of action of fosfomycin (phosphomycin). Ann. N.Y. Acad. Sci. 235:364-386. 7. Lerner, S. A., S. Price, and S. Kulkarni. 1988. Microbiological studies of fosfomycin trometamol against urinary isolates in vitro, p. 121-128. In H. C. Neu and J. D. Williams (ed.), New trend in urinary tract infections: the single-dose therapy. S. Karger AG, Basel. 8. LiPira, G., C. Pruzzo, and G. C. Schito. 1987. Monuril and modification of pathogenicity traits in resistant microorganisms. Eur. Urol. 13(Suppl. 1):92-97. 9. National Comnmittee for Clinical Laboratory Standards. 1990. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A2, 2nd ed.
National Committee for Clinical Laboratory Standards, Villanova, Pa. 10. Wise, R., and J. M. Andrews. 1988. Fosfomycin trometamol: an in vitro study, p. 232-241. In H. C. Neu and J. D. Williams (ed.), New trend in urinary tract infections: the single-dose therapy. S. Karger AG, Basel.
