The Clinical Microbiology Institute, 9725 SW Commerce Circle, Suite A-1, Wilsonville, OR 97070, USA
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Abstract |
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Introduction |
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MK-0826 (L-749,345) is a new oral carbapenem with broad spectrum antimicrobial activity. The present study was designed to: (i) define the in-vitro antibacterial activity of MK-0826, in comparison with imipenem, against a broad variety of common species of aerobic and facultatively anaerobic bacteria, and (ii) determine tentative interpretive criteria for disc diffusion tests using commercially prepared 10 µg MK-0826 discs.
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Materials and methods |
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A collection of 545 bacterial isolates representing 34 species was selected from our stock culture collection of clinical isolates. The individual species and the number of isolates of each species are listed in the Table. Two or more of the following quality control (QC) isolates were tested on each test day: Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213 (dilution tests only), S. aureus ATCC 25923 (disc tests only), Enterococcus faecalis ATCC 29212 (dilution tests only) and Streptococcus pneumoniae ATCC 49619. All 30 disc diffusion and all 59 broth microdilution susceptibility tests of imipenem were within published QC ranges. 5,6
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The study drugs, MK-0826 and imipenem, were provided as standardized powder by Merck, Sharp and Dohme (Rahway, NJ, USA). For the disc diffusion studies, commercially prepared 10 µg MK-0826 discs (BBL 508649) and 10 µg imipenem discs (BBL 501629) were used.
Test procedures
Disc diffusion and broth microdilution susceptibility tests were those outlined by the National Committee for Clinical Laboratory Standards (NCCLS). 5,6 When testing streptococci, the cation adjusted MuellerHinton broth was supplemented with 23% lysed horse blood to support growth and the agar contained 5% sheep blood.
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Results and discussion |
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The Figure displays a scattergram comparing MK-0826 MICs and disc
diffusion zone diameters.
The zone diameter breakpoints were determined for possible MIC breakpoints of 2.0 or
4.0 mg/L for susceptible and
8.0 or
16 mg/L for resistant. The MIC breakpoint
ultimately selected will depend on continuing pharmacokinetic studies and clinical data. With
the
4.0 mg/L susceptible MIC breakpoint, the zone diameter breakpoints would be
16
mm for susceptible and
12 mm for resistant. With those breakpoints interpretive discrepancy
rates were very low, i.e. no very major discrepancies, 0.2% major discrepancies, and
4.4% minor
discrepancies. With a susceptible MIC breakpoint of
2.0 mg/L, the zone diameter
breakpoints would be 3 mm larger, with no major discrepancies, 0.8% very major
discrepancies
and 2.9% minor discrepancies. The corresponding discrepancy rates for imipenem disc
tests were
1.2%, 0 and 0.8%, respectively.
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Acknowledgments |
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Notes |
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References |
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2 . Kropp, H. L., Gerckens, L., Sundelof, J. G. & Kahan, F. M. (1985). Antibacterial activity of imipenem: the first thienamycin antibiotic. Review of Infectious Diseases 7 , Suppl. 3, S389410.[ISI][Medline]
3 . Malanoski, G. J., Collins, L., Wennersten, C., Moellering, R. C. & Eliopoulos, G. M. (1993). In-vitro activity of biapenem against clinical isolates of Gram-positive and Gram-negative bacteria. Antimicrobial Agents and Chemotherapy37 , 200916.[Abstract]
4 . Neu, H. C. & Labthavikul, P. (1982). Comparative in-vitro activity of N-formimidoyl thienamycin against Gram-positive and Gram-negative aerobic and anaerobic species and its ß -lactamase stability. Antimicrobial Agents and Chemotherapy21 , 1807.[ISI][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.
Received 16 September 1998; returned 11 November 1998; revised 7 December 1998; accepted 6 January 1999