The BACTEC™ MGIT™ 960 SIRE Kit is used as a rapid qualitative procedure for susceptibility testing of Mycobacterium tuberculosis, from culture, to streptomycin, isoniazid, rifampin and ethambutol using the BACTEC™ MGIT™ 960 System.

Antimycobacterial susceptibility testing is necessary for the proper treatment of patients with tuberculosis. The treatment of tuberculosis is commonly through a multiple drug regimen which includes the antimycobacterial drugs streptomycin, isoniazid, rifampin and/or ethambutol. It is important that the antimycobacterial drugs prescribed show appropriate activity against Mycobacterium tuberculosis, i.e., susceptibility of the isolate to the drug.

Multidrug resistant Mycobacterium tuberculosis (MDR-TB) has recently become a serious public health problem.¹ Resistance to any of the four primary drugs, streptomycin (STR), isoniazid (INH), rifampin (RIF), and ethambutol (EMB), makes the disease more difficult and expensive to treat. The rapid detection of these strains is critical to the effective treatment of the patient.

Two methods have been widely used for antimycobacterial susceptibility testing. The first method, known as the Method of Proportion,² uses Middlebrook and Cohn 7H10 Agar. It compares colony counts on drug-containing and drug-free media. Resistance to a drug is detected when 1% or more of the bacterial population is resistant to the drug concentration under test. Results are generally available after 21 days of incubation. The second method, known as the BACTEC™ 460TB radiometric susceptibility method,³ generally takes from 4 to 12 days. It is based on the production of radioactive ¹⁴C-labeled carbon dioxide by the growing mycobacteria, manifested by a growth index increase in the system.

Historically, the Method of Proportion (MOP) procedure has included susceptibility testing of Mycobacterium tuberculosis using two concentrations of antimicrobials. The National Committee for Clinical Laboratory Standards (NCCLS) continues to recommend that the MOP test procedure include two concentrations of the primary drugs for testing except rifampin. The recommended low concentrations for the MOP procedure are generally considered to be the critical concentrations for these drugs. The critical concentration is defined as the drug concentration which inhibits the wild type sub-population while allowing sufficient growth of the mutant resistant sub-population in order to determine resistance at the critical proportion of 1%. The high drug concentration is not considered to be the critical concentration. However, resistance at the high concentration is evidence that resistance is generally distributed among the population of the test M. tuberculosis strain. Some clinicians use the susceptibility test results at the high concentrations to profile the degree of resistance of the test strain.

The BACTEC™ MGIT™ 960 SIRE test provides the susceptibility result in approximately the same time frame as the BACTEC™ 460TB system. In addition, this method is non-radiometric and allows appropriate antibiotic susceptibility results to be reported earlier, in most cases, than with the MOP procedure.

The BACTEC MGIT 960 system has been developed to allow susceptibility testing at the critical concentration for streptomycin, isoniazid, rifampin and ethambutol, and at a higher concentration for streptomycin, isoniazid, and ethambutol. These concentrations correlate with the two concentrations used in the MOP procedure. A susceptible result at the critical concentration can be reported and no other tests are necessary. However, any strain determined to be resistant with the BACTEC MGIT 960 SIRE kit to streptomycin, isoniazid, and ethambutol at the critical concentration may be, at a minimum, tested at the high concentration. In this case, a final result of resistant at the critical concentration may be reported, with notification that an additional test at the high concentration is being performed.