3.5 Methods of definition of drug resistance


The mycobacterium strains considered to be sensitive to the given drug refer those when critical drug concentration (criteria of resistance) causes bactericidal or bacteriostatic action.
The tolerance (resistance) is defined as reduction of sensitivity to such degree, that given strain of mycobacterium is capable to multiply in condition of action of the drug’s critical or higher concentration. Alongside with concepts “sensitivity” and “resistance” to antituberculous drugs the terms determining the quantitative and qualitative characteristics of drug resistance now are used also. So, in case of presence of drug resistance to two or more preparations given strain of mycobacterium is defined as multidrug resistant.

Definitions of drug resistant tuberculosis.

Acquired (secondary) resistance – cases in which the strain of tubercle bacilli change from a susceptible into resistant phenotype during or following a course of chemotherapy. In these instances, “inadequate” treatment selects for emergence of drug-resistant mutants. Among patients with histories of 1 month or more of prior treatment, is inferred that this treatment has caused acquired resistance (however, unless the initial susceptibility pattern at the onset of therapy is known, initial or trans¬mitted resistance cannot be excluded).

Primary resistance.
In some cases, patients are found on initial medical encounters to harbor a strain of tuberculosis involving significant resistance to a single drug or resistance to several agents. Primary resistance: when the person is infected by someone who has tubercle bacilli with acquired resistance to one or more drugs.

Combined resistance.
The World Health Organization sums primary and acquired to determine the overall or combined prevalence of resistance.

Transmitted resistance.
Tuberculosis involving strains with high-level, clinically significant drug resistance that have been spread recently from known contacts with similar patterns of resistance. Strain identity is proven by resistance pattern or restriction fragment length polymorphism (RFLP) “fingerprinting.”

Monoresistance – MBT Strains that are resistant to only one of the five first-line drugs: rifampicin, isoniazid, ethambuto, pyrazinamide, streptomycin.

MDR (Multi-Drug Resistant) bacilli and MDR tuberculosis is the most severe form of bacterial resistance today. It is why MDR tuberculosis is an important concern for tuberculosis control in many countries.

Multidrug resistance (MDR) – MBT strains that are resistant to both isoniazid and rifampicin; there may be additional resistance to other antituberculosis drugs.

Polyresistance (compound) resistance – MBT srains that are resistant to two or more drugs but not to both isoniazid and rifampin.

Since the early 1990s, several outbreaks of MDR tuberculosis have been reported in different regions of the world, as a consequence of inappropriate use of essential antituberculosis drugs. Usually MDR tuberculosis occurs in chronic cases, after failure of WHO or other retreatment regimens and represents a significant proportion of tuberculosis patients with acquired resistance..

Criteria of drug resistance.

The level of given strain resistance is expressed by that maximal concentration of a preparation (microgram quantity in 1 ml of media), at which the duplication of the MTB (according to number of colony formation on dense media) is still observed.

The drug resistant microorganisms are capable to multiply at such contents of the drug in media, which on sensitive mycobacterium has bacteriostatic or bactericidal action. The critical concentration is adopted for different antituberculouse drugs. The critical concentration have clinical importance, because it shows the concentration of the drug in media at which MBT duplication sensitive to this preparation is still observed.

Method of absolute concentrations in Lowenstein-Jensen inspissated egg media widely used for the definition of MBT drug resistance.

Genomic Analysis for Drug Susceptibility Testing.
The genetic loci of resistance mutations for isoniazid, rifampin, ethambutol, streptomycin, and the fluoroquinolones have been identified. Based on this type of methodology, molecular-biological techniques are rapidly improved and offer quick identification of the susceptibility profile of a clinical MBT strains.

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