Резюме
Шевченко О.С. Мультирезистентний туберкульоз: характеристика профілей резистентності виділених штамів M. tuberculosis.
Метою дослідження було визначити профілі медикаментозної стійкості штамів МБТ до протитуберкульозних препаратів I та II ряду у хворих на МРТБ зареєстрованих в 2011-2012 рр. в Харківській області. Аналіз показав несприятливу тенденцію збільшення сумарної частоти медикаментозної стійкості МБТ і ускладнення її структури. Особливістю сучасної епідеміологічної ситуації по туберкульозу є зростання частоти первинної лікарської стійкості.
Ключові слова: туберкульоз, лікарська стійкість, епідеміологія.
Резюме
Шевченко О.С. Мультирезистентный туберкулез: характеристика профилей резистенстности выделенных штаммов M. tuberculosis.
Целью данного исследования явилось установить профили медикаментозной устойчивости МБТ к  противотуберкулезным препаратам I и II ряда у больных с МРТБ зарегистрированных в 2011-2012 гг. в Харьковской области. Анализ показал неблагоприятную тенденцию увеличения суммарной частоты медикаментозной устойчивости МБТ и утяжеление ее структуры. Особенностью современной эпидемиологической ситуации по туберкулезу является возрастание частоты первичной лекарственной устойчивости.
Ключевые слова: туберкулез, лекарственная устойчивость, эпидемиология.
Summary
Shevchenko O.S. Multi-drug-resistant tuberculosis: profiles of resistance of the isolated strains of M. tuberculosis.
It was to set the types of drug resistant of AFB the purpose of this research to anti-tuberculosis drugs I and the II row for patients with MDR incorporated in 2011-2012 in the Kharkov region. An analysis showed the unfavorable tendency of increase of total frequency of drug resistant of AFB and making of her structure heavier. The feature of modern epidemiology situation on tuberculosis is growth of frequency of primary medicinal stability.
Key words: tuberculosis, drug resistance, epidemiology.
Рецензент: д.мед.н., проф. Ю.Г. Пустовий

УДК 616.24-0025:579.873.21]-085.015.8

Харьковский национальный медицинский университет

проспект Ленина, 4, Харьков, 61022,Украина 

Kharkiv National Medical University,

4 Lenin Avenue, Kharkiv,61022,Ukraine

lazur13@mail.ru

One of the main reasons that hamper the control of the TB situation in the world, including Ukraine, is the rapid spread of resistant strains of Mycobacterium tuberculosis (MBT) to anti-TB drugs. First official information WHO concerning resistant tuberculosis was published in 1997, and in 1999, given the extent of the problem, was published "DOTS-Plus for multidrug-resistant tuberculosis" program, which resulted in the new term in the structure of tuberculosis epidemic – multidrug-resistant tuberculosis (MDR TB). Among the countries of the Eastern Europe region, Ukraine, in terms of the prevalence of multidrug-resistant tuberculosis, is one of the unfavorable places. The share of this form of TB among new and recurrent cases of MDR TB treatment was: Bulgaria – 2, 0 and 24%, Armenia – 9, 4 and 43%, Georgia – 9, 5 and 31%, Latvia – 10 and 24%, Lithuania – 11 and 52%, Kyrgyzstan – 14 and 39%, Kazakhstan – 14 and 45%, Uzbekistan – 14 and 49%, Ukraine – 16 and 44%, Tajikistan – 17 and 62%, Estonia – 18 and 44%, the Russian Federation – 18 and 46%, Moldova – 19 and 65%, Azerbaijan – 22 and 56% respectively (according to the WHO in 2010-2011.) [5, 6, 7].

WHO estimates that between 2011 and 2015 there will be found more than 2 million of new cases of MDR TB. According to the latest data, every year the world reveals about 450 000 new cases of MDR TB, with countries such as China, India and Russia for more than 50% of all cases in the world. In 2011, in most countries, less than 5% of new and previously treated TB patients were tested for MDR TB and only 20% of registered patients receive adequate therapy. [7]

Treatment of drug-resistant forms of the disease is partly complicated by the fact that it involves the use of expensive and toxic drugs. [3]. In this case, low-income countries report a shortage of funding in 2012 to 1 billion U.S. dollars. [4].

The official registration of MDR TB cases in Ukraine was introduced in 2010. Multiresistance of newly diagnosed cases of tuberculosis is about 10%, re-treatment – up to 40%.

Every year there is increasing evidence of retrospective and prospective studies which find the expansion of the profile of resistance to first-line and second-line antitubercular drugs [1, 2].

The purpose of this study was to establish profiles of m.tuberculosis drug resistance to first-line and second-line drugs in MDR TB patients registered in 2011-2012 in Kharkiv region.

Materials and Methods

We conducted a retrospective research of 445 MDR TB patients with pulmonary tuberculosis registered in the database of registration office and case management of chemoresistant tuberculosis during 2011-2012 in the Regional Tuberculosis Dispensary № 1 in Kharkov.

Analyzing the registration teams (according to the order of Ministry of Health of Ukraine of 22. 10. 2008 № 600) [3], according to the medical history of previous treatment, or, based on the results of previous treatment cohort analysis, the patients were as follows: in the first category – ‘new case’ –151 patients registered (33, 9%), in the second category – ‘relapse TB’ – 79 patients (17, 7%), in the third category – 'interrupted treatment’ – 50 patients (11, 2%), in the fourth category – ‘failure of the first course of chemotherapy’ – 39 patients (8, 8%), in the fifth category – ‘repeated failure of chemotherapy’ – 48 patients (10, 8%), the sixth category – ‘transferred’ – 13 patients (2, 9 %), and in the seventh category – ‘the other’ – 65 patients (14, 6%).

All patients had bacterial excretion confirmed by culture sputum method. The Mycobacterium tuberculosis medical sensitivity test to first-line and second-line anti-tubercular drugs (ATP) was conducted on the colonies that had grown on the standard liquid and solid substrata. [4]

The obtained data were processed on a computer using the statistical program STATISTICA. Below are the results of the research profiles of M.tuberculosis resistance cultures in MDR TB patients over the period of 2011-2012.

Results and Discussion.

When considering the total number of strains isolated in patients with pulmonary tuberculosis over the period of  2011-2012, we found that the fully susceptible M.tuberculosis strains is 65, 1% of all cases; the multiresistant strains are 23, 2% of all cases of the bacterial population studied over the period of 2 years.

In the MDR TB group with drug-resistance only to first-line drugs – 208 patients (46, 7%) – more common were strains resistant to four drugs (HRES) and amounted to 68, 7% of cases (143 patients); almost 2, 5 times less frequent were strains resistant to the three drugs (HRS) simultaneously – 27, 9% of the cases (58 patients). The total frequency resistance of MBT to streptomycin was 96, 6%, to ethambutol – 70, 2%.

237 MDR TB patients (53, 3%) had strains resistant to first-line and second-line drugs simultaneously, of those – 46 patients (10, 3% of 445 MDR TB patients) were extensively drug-resistant.

Strains resistant to four drugs (HRES), were found in 71, 7% of cases (170 patients), and strains resistant to three drugs (HRS) – in 28, 3% of the cases (67 patients). The total frequency resistance of MBT to streptomycin was 97, 0%, to ethambutol – 64, 9%.

When analyzing 445 MDR TB cases, we found that the overall detection rate of strains resistant to amikacin was 18, 6%; kanamycin – 35, 5%; capreomycin – 14, 8%, to all injecting drugs simultaneously (AmKmCm ) – 12, 4%; fluoroquinolone – 14, 2%. The total detection rate of strains resistant to ethionamide was 19, 8%; to prothionamide – 14, 2%; to PAS – 7, 9% of the cases.

After analyzing, we can establish an unfavorable tendency of the total frequency of MBT drug resistance to increase and weighting of its structure. Over the period of 2009-2012, the total frequency of MBT resistance to anti-TB drugs in MDR TB patients increased: to streptomycin from 86, 8 to 91, 7%; to ethambutol from 55, 3% to 63, 8%. And, more often, the resistance to all first-line drugs (HRES) is diagnosed; whereas in 2009 the figure was 67, 5%, in 2012 – 72, 9% of all MDR TB cases.

It is curious that in the study group, the patients co-infected with TB / HIV were registered 25 people (5, 6%), of those 96% showed strains resistant to 3 anti-tubercular drugs (HRS); cases of extensive drug-resistance to anti-tubercular drugs have not been identified.

While analyzing the effectiveness of the treatment of MDR TB patients over the period of 2011-2012, we detected that in ‘residual changes after suffering tuberculosis’ had been transferred five patients, which was 1, 1% of the cases, fatal outcome was recorded in 46 patients (10, 3%).

After analyzing the profiles of multidrug-resistant tuberculosis, we can establish the fact of high frequency of occurrence of primary drug resistance in our population, as evidenced by 33, 9% of the reported cases in the first category - the ‘new case.’ Of the factors contributing to the emergence of MBT secondary resistance, the most common are cases of recurrent tuberculosis, chronic TB and repeated failure of chemotherapy. Such threatening statistics is due to difficulties in early MDR TB diagnosis, undisciplined and unconscious patients, avoiding systematic receiving anti-TB drugs on various excuses, as well as due to difficulties in the acquisition of high-quality second-line drugs in full.

Conclusions:

1. Today, the majority of verified MDR TB patients are patients with newly diagnosed tuberculosis and recurrent tuberculosis, with primary resistance of M.tuberculosis being 33, 9% of the cases.

2. Of MDR TB patients, the most common are strains of M.tuberculosis with HRES-resistance profile – followed by sensitivity to second-line drugs, as well as with additional resistance to the different number of second-line anitubercular drugs.

3. Wide prevalence of MDR TB patients drug resistance amounted to 10, 3%.

4. Apart from resistance to isoniazid and rifampicin, MDR TB patients the most frequently showed resistance to streptomycin – 96, 8%, to ethambutol – 67, 4%; kanamycin – 35, 5%, to ethionamide – 19, 8%; to amikacin – 18, 6%; to capreomycin – 14, 8%, to fluoroquinolones – 14, 2%.

Література
1. Клініко-лабораторні особливості перебігу мультирезистентного туберкульозу легень в Україні / І.В. Ліскіна, С.Д. Кузовкова, О.А. Журило, А.І. Барбова [и др.] // Туберкульоз, легеневі хвороби, ВІЛ-інфекція. − 2011. – № 2 (05). – С. 5-10.
2. Лепшина С.М. Проблемы химиорезистентного туберкулеза на современном этапе / С.М. Лепшина // Архив клинической и экспериментальной медицины. − 2008. – Т 17, № 1. – С. 77-80.
3. Наказ МОЗ України від 22.10.2008 № 600 «Про затвердження стандарту надання медичної допомоги хворим на хіміорезистентний туберкульоз».
4. Наказ МОЗ України від 06.02.2002 № 45 «Про затвердження Інструкції з бактеріологічної діагностики туберкульозної інфекції».
5. Caminero J.A. Multidrug-resistant tuberculosis: epidemiology, risk factors and case finding / J.A. Caminero // Int. J. Tuberc. Lung Dis. - 2010. – Vol. 14(4). – P. 382-390.
6. Chiang C.Y. Drag-resistant tuberculosis:bpast, present, future / C.Y. Chiang, R. Centis, G.B. Migliori // Respirology. – 2010. – Vol. 15(3). – P. 413-432.
7. Global Tuderculosis Сontrol: surveillance, planning, financing: WHO report 2010. – Geneva: Switzerland, 2010. –383 p.