Session: Novel b-Lactams and b-Lactamase Inhibitors
Location:
Exhibit Hall
Session Date:
Sunday, 9/26/99
Session Time:
1:30 pm - 3:00 pm
Pilot Study of RWJ-54428 (MC-02,479): Correlation of Broth Microdilution Susceptibility Testing
Results with Disk Diffusion Zone Diameters
B. Foleno1, J.J. Hilliard1, D.A. Montenegro1, J. Blais2, S. Chamberland2, M. Dudley2, M.
Hoang2, G. Miller2, K. Bush1
1R. W. Johnson PRI: Raritan, NJ; 2Microcide Pharmaceuticals: Mountain View, CA
RWJ-54428 (MC-02,479) is a novel cephalosporin with good antibacterial activity against Gram-positive
pathogens, including MRSA, methicillin-resistant coagulase negative staphylococci, multi-drug-resistant
streptococci and vancomycin-susceptible and -resistant enterococci. To begin development of a disk for
diagnostic use, broth microdilution MICs and zone diameters for RWJ-54428 against 157 isolates were
measured in two laboratories. Disks were prepared with 2.5, 5.0 or 10 mg of RWJ-54428 by dissolving the
cephalosporin in 95% ethanol, drying either in air for 1 hour or for 30 minutes at 45oC, and storing at 4oC,
-20oC or -70oC. Results:
MIC
Zone Diameter (mm) for Disk Content
Organism
N
(mg/ml)
2.5 mg
5.0 mg
10 mg
Staphylococci
66
£0.06 - 4
12 - 35
17 - 37
21 - 42
Streptococci
26
£0.06 - 0.5
19 - 40
20 - 41
23 - 45
Enterococci
35
£0.06 - 8
6 - 25
6 - 28
13 - 31
Gm negatives
30
1 - >128
6 - 15
6 - 19
6 - 22
Correlation Coefficient*
0.89
0.90
0.91
*Linear regression analysis only for organisms with MIC endpoints
Zone sizes were largest for the most sensitive streptococci. Regression statistics were similar for all disks
tested. The 5.0 and 10 mg disks were stable (£ 1 mm diameter change in repetitive testing against S. aureus
ATCC 25923) over a period of at least 3 weeks. Additional studies will be needed to determine the
susceptibility breakpoint for this cephalosporin. Either a 5.0 mg or 10 mg disk is a good candidate for further
development. |
