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Clinical Pharmacology
Biaxin
Note: When testing Streptococcus spp., including Streptococcus pneumoniae, susceptibility and resistance to clarithromycin can be predicted using erythromycin.
Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for clarithromycin.
As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 15-μg clarithromycin disk should provide the following zone diameters in this laboratory test quality control strain:
Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for clarithromycin. As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 15-μg clarithromycin disk should provide the following zone diameters in this laboratory test quality control strain:
| Microorganism | Zone diameter (mm) | |
| S. aureus | ATCC 25923 | 26 to 32 |
| S. pneumoniaeg | ATCC 49619 | 25 to 31 |
| Haemophilus influenzaeh | ATCC 49247 | 11 to 17 |
| g This quality control range is applicable
only to tests performed by disk diffusion using Mueller-Hinton agar supplemented
with 5% defibrinated sheep blood. h This quality control limit applies to tests conducted with Haemophilus influenzae ATCC 49247 using HTm². |
||
In vitro Activity of Clarithromycin against Mycobacteria
Clarithromycin has demonstrated in vitro activity against Mycobacterium avium complex (MAC) microorganisms isolated from both AIDS and non-AIDS patients. While gene probe techniques may be used to distinguish M. avium species from M. intracellulare, many studies only reported results on M. avium complex (MAC) isolates.
Various in vitro methodologies employing broth or solid media at different pH's, with and without oleic acid-albumin-dextrose-catalase (OADC), have been used to determine clarithromycin MIC values for mycobacterial species. In general, MIC values decrease more than 16-fold as the pH of Middlebrook 7H12 broth media increases from 5.0 to 7.4. At pH 7.4, MIC values determined with Mueller-Hinton agar were 4- to 8-fold higher than those observed with Middlebrook 7H12 media. Utilization of oleic acid-albumin-dextrose-catalase (OADC) in these assays has been shown to further alter MIC values.
Clarithromycin activity against 80 MAC isolates from AIDS patients and 211 MAC isolates from non-AIDS patients was evaluated using a microdilution method with Middlebrook 7H9 broth. Results showed an MIC value of ≤ 4.0 μg/mL in 81% and 89% of the AIDS and non-AIDS MAC isolates, respectively. Twelve percent of the non-AIDS isolates had an MIC value ≤ 0.5 μg/mL.
Clarithromycin was also shown to be active against phagocytized M. avium complex (MAC) in mouse and human macrophage cell cultures as well as in the beige mouse infection model. Clarithromycin activity was evaluated against Mycobacterium tuberculosis microorganisms. In one study utilizing the agar dilution method with Middlebrook 7H10 media, 3 of 30 clinical isolates had an MIC of 2.5 μg/mL. Clarithromycin inhibited all isolates at > 10.0 μg/mL.
Susceptibility Testing for Mycobacterium avium Complex (MAC)
The disk diffusion and dilution techniques for susceptibility testing against gram-positive and gram-negative bacteria should not be used for determining clarithromycin MIC values against mycobacteria. In vitro susceptibility testing methods and diagnostic products currently available for determining minimum inhibitory concentration (MIC) values against Mycobacterium avium complex (MAC) organisms have not been standardized or validated. Clarithromycin MIC values will vary depending on the susceptibility testing method employed, composition and pH of the media, and the utilization of nutritional supplements. Breakpoints to determine whether clinical isolates of M. avium or M. intracellulare are susceptible or resistant to clarithromycin have not been established.
Susceptibility Test for Helicobacter pylori
Generic Name: Clarithromycin
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