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 TREATMENT SPECIFICITIES OF PULMONARY TUBERCULOSIS CAUSED BY DRUG RESISTANT MYCOBACTERIA 
KAKHA VACHARADZE, Doctor of Medicine, M.D
TSMU phthisiatric department, Professor.
Georgian Respiratory Association, Vice-President.
European Respiratory Association, Real member.
Georgian Phthisiatric Association, Board Member.
Member of Georgian Surgery Association.
Founder of Georgian Bronchopulmonologists Association.
 
 
    10 million people are affected by tuberculoses annually in the word and 3 million of them die of it. Among them 8 thousand people dies during one day. These are not complete statistical data. According to the data provided by World Health Organization, every third inhabitant of the earth has tuberculosis causing bacteria in the organism. It is expected that number people reinfected with tuberculosis will be over 200 million and 70 million of them will die from this disease by 2010 year. Such scary statistics gives us the basis for paying attention to the methods of treatment and epidemiology of this perfidious infection, especially when the drug resistance of mycobacterium represents the main limitation of the effective antituberculous treatment. Index of drug resistance varies in different countries. The incidence of tuberculosis in Georgia was 134, 2 cases on every 100 000 population in 2004 year and 146, 5 cases in 2005 year. Hipotetical quantity of multi drug resistant tuberculosis (MDR-TB) cases is based on data received in advance from the drug sensitivity test (DST) 2005-2006 years) and represents 6,8% of new cases and 27,4% of cases already treated in the past. In the patient with new disease resistance is revealed in 515 cases, while in patients with already treated disease the resistant were 799 cases in the whole population.
Clinical effectiveness of antituberculous preparations is defined by many factors. The main of which are: 
·        Quantity of micobacteries in population 
·        Sensitivity or resistance of mycobacteria to the used drugs in the population.
·        High growth rate of specific mycobacteria
·        Bacteriostatic concentration
·        Drug penetrability and effectivity in the lesion.
·        Drug ability to affect extracellular and intracellular (phagocytized) bacteria.
·        Patient tolerance to drug. 
When we speak about resistant tuberculosis it is important to specify definitions and terminology:  
·        Mycobacterium, which causes DR-TB, may be naturally (primary resistance) resistant to the antiTB drugs of may acquire resistance secondarily. 
·        Mycobacterium causing Single Drug-Resistant Tuberculosis (SDR-TB) is resistant to only one antiTB drug.
·        Mycobacteria causing Multi Drug-Resistant Tuberculosis (MDR-TB) is resistant at least to the isoniazid and rifampicin.
·        Mycobacteria causing Extensive Drug-Resistant Tuberculosis (EDR-TB) is resistant to izoniazid and rifampicin, to one represantative of fluoroquinolone family and one of the injectional medications (canamicin, amikacin, kapreomicin). 
·        The main anti-TB medications isoniazid, rifampin, pyrazinamid, ethembutol and spreptomicyn are highly effective against mycobacterium. Etiotropic treatment of resistant tuberculosis is much more difficult because effectivity of chemotherapy depends on drug resistance frequency and nature. Specific pulmonary tuberculous lesion caused by resistant mycobacteria has especially difficult course.
 
 The main risk-factor for the development of this form of disease is noneffective primary and especially interrupted treatment. The main goal of avoidance of drug resistance development is to treat patients with primary tuberculosis according to modern, scientifically approved clinical methods. Based on the different condition of mycobacterial culture in the different phases of the disease it is important to divide treatment of tuberculosis in tow steps or phases: initial or intensive phase is directed to the fast dividing population with active metabolism, to inhibit drug resistant mutants, to decreases quantity of population and to avoid development of secondary resistance.   For the treatment of drug sensitive tuberculosis are used four anti-TB preparations: isoniazid, rifampincin, athambutol or streptomycin during tow month, followed by two drugs – isoniazid and rifampicin for four month. isoniazid, rifampicin and pyrazinamid represent the basis of initial phase treatment. Also, it should be mentioned that both drugs are equally effective against all populations of mycobacteria in the center of the inflammation. Isoniazid has bactericidal effect on mycobacteria sensitive to both antibiotics and kills rifampicin-resistant organisms, while the rifampicin also destroys organisms sensitive to both preparation and that is especially important, has bactericidal effect on isoniazid-resistant rods.
The second phase of the treatment the main goal of this step is to avoid replication of remaining bacteria and to stimulate repair processes in the lungs. Conductance of the whole course of treatment demands patience and great endurance from the patient. Patient compliance to the physician’s recommendations can give the exact prediction of treatment outcome.     The regime of anti- TB treatment – optimal combination of anti-TB preparations, drug dosage, the rotes of antibiotic introduction and treatmetn duration are defined with the foreseeing of following factors: 
-         epidemiologic danger (patient contagiosity)
-         disease character (primary case, recurrent disease or chronic form)
-         severity and spreading of the primary process.
-         drug resistance of mycobacteria.
    For the treatment of multiresistant tuberculosis (MRD-TB) folloving drug combinations are used: amicacin (merkacin), isoniazid, rifampicin (rifabutin), ethambutol, pyrasinamide, ftourquinolones.
Merkacin is the III generation aminoglicoside and belongs to the second line antituberculous preparations according to all guidelines. Quality of merkacin completely satisfies the strict requests of modern pharmacopeia and it may be used for the treatment of proved resistant tuberculosis and also as empirical treatment in suspicious cases.
Merkacine as the wide spectrum bactericidal antibiotic has great role in the treatment of patients with resistant tuberculosis, because the specific process is often accompanied by sever hospital superinfection (Pseudomona aeruginosa, Acinetobacter spp. etc.), which worsens the course of the process. From this point of view, it is important to incorporate mercacin in the treatment scheme which will eliminate bacteria and will stimulate reparation processes in tissue. Also merkacin does not lose its effectiveness by action of bacterial ferments and preserves its effectivity even in the presence of resistance (gentamicin, canamicin, netilmicin, sizomicin).
Also it should be mentioned that bioavailability of merkacin is 100%. Its concentration in the pleural fluid is 80% of the plasma level and effective bactericidal concentration is present in blood for 12 hours. Dose regime of merkacine in the patients with resistant tuberculosis, is 1 g a day, divided in tow doses. Maximal daily dose is 1, 5 g. After the patient becomes culture negative, it is possible to decrease merkacin dose to once daily usage three times a week. 
Intensive phase of MRD-TB treatment is 3 months and the next phase – 9 months. The length of whole treatment depends on the speed of process involution. Such intensity of the treatment gives us possibility to stop bacterial discharge and avoid recurrence and chronicity of the process. 
References:
1. Мишин В.Ю. Современные режимы химиотерапии туберкулезаа легких, вызванного лекарственно-чувствительными и лекарственно-резистентными микобактериями
2. Варен Ф., Аргулаин. Э., Гиулсон К., Салакаия А. Гаидлаин резистентного туберкулеза. 2006.