Rifampin microbiology

Rifampin
FDA Package Insert (Rifadin®)
Description
Clinical Pharmacology
Microbiology
Indications and Usage
Contraindications
Warnings and Precautions
Adverse Reactions
Overdosage
Dosage and Administration
How Supplied
Labels and Packages

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]

Microbiology

Mechanism of Action

Rifampin inhibits DNA-dependent RNA polymerase activity in susceptible Mycobacterium tuberculosis organisms. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme.

Drug Resistance

Organisms resistant to rifampin are likely to be resistant to other rifamycins. In the treatment of both tuberculosis and the meningococcal carrier state (see INDICATIONS AND USAGE), the small number of resistant cells present within large populations of susceptible cells can rapidly become predominant. In addition, resistance to rifampin has been determined to occur as single-step mutations of the DNA-dependent RNA polymerase. Since resistance can emerge rapidly, appropriate susceptibility tests should be performed in the event of persistent positive cultures.

Activity in vitro and in vivo

Rifampin has bactericidal activity in vitro against slow and intermittently growing M tuberculosis organisms.

Rifampin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the Indications And Usage section.

• Aerobic Gram-Negative Microorganisms:

Neisseria meningitidis

• "Other" Microorganisms:

Mycobacterium tuberculosis

The following in vitro data are available, but their clinical significance is unknown.

Rifampin exhibits in vitro activity against most strains of the following microorganisms; however, the safety and effectiveness of rifampin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials.

• Aerobic Gram-Positive Microorganisms:

Staphylococcus aureus (including Methicillin-Resistant S. aureus/MRSA)

Staphylococcus epidermidis

• Aerobic Gram-Negative Microorganisms:

Haemophilus influenzae

• "Other" Microorganisms:

Mycobacterium leprae

β-lactamase production should have no effect on rifampin activity.

Susceptibility Testing

Prior to initiation of therapy, appropriate specimens should be collected for identification of the infecting organism and in vitro susceptibility tests.

In vitro testing for Mycobacterium tuberculosis isolates:

Two standardized in vitro susceptibility methods are available for testing rifampin against M tuberculosis organisms. The agar proportion method (CDC or CLSI(1) M24-A) utilizes Middlebrook 7H10 medium impregnated with rifampin at a final concentration of 1.0 mcg/mL to determine drug resistance. After three weeks of incubation MIC99 values are calculated by comparing the quantity of organisms growing in the medium containing drug to the control cultures. Mycobacterial growth in the presence of drug, of at least 1% of the growth in the control culture, indicates resistance.

The radiometric broth method employs the BACTEC 460 machine to compare the growth index from untreated control cultures to cultures grown in the presence of 2.0 mcg/mL of rifampin. Strict adherence to the manufacturer's instructions for sample processing and data interpretation is required for this assay.

Susceptibility test results obtained by the two different methods can only be compared if the appropriate rifampin concentration is used for each test method as indicated above. Both procedures require the use of M tuberculosis H37Rv ATCC 27294 as a control organism.

The clinical relevance of in vitro susceptibility test results for mycobacterial species other than M tuberculosis using either the radiometric or the proportion method has not been determined.

In vitro testing for Neisseria meningitidis isolates:

Dilution Techniques

Quantitative methods that are used to determine minimum inhibitory concentrations provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure uses a standardized dilution method2,4 (broth, agar, or microdilution) or equivalent with rifampin powder. The MIC values obtained should be interpreted according to the following criteria for Neisseria meningitidis:

References

Adapted from the FDA Package Insert.