[The course of a process and the efficiency of treatment of pulmonary tuberculosis patients excreting Mycobacterium tuberculosis with extensive drug resistance to antituberculous drugs].

Forty-one pulmonary tuberculosis patients (32 males and 9 females) excreting Mycobacterium tuberculosis (MBT) with extensive drug resistance to antituberculous drugs were examined. The process was first detected in 14.6% of the patients. At the previous stage of treatment, the vast majority of patients (85.4%) received antituberculous drugs. Fibrocavernous tuberculosis was a predominant form (73.1%). The acutely progressive course of the process was observed in 29.3% of patients. Lung destructive changes and bacterial excretion were revealed in all (100%) patients. Resistance to streptomycin, isoniazid, rifampicin, and fluoroquinolones was seen in all (100%) patients. The fact that in this cohort of patients the resistance of MBT to reserve drug, such as kanamycin, amikacin, and cycloserine, is observed at a rather high rate (from 58.5 to 73.1%) is concerned about. For evaluation of the efficiency of treatment, all the examinees were divided into 2 groups, which were equal in clinical and laboratory characteristics. Group 1 patients (n = 19) were given chemotherapy regimen 2b (in new cases of tuberculosis) and individual chemotherapy regimens. Collapse therapy was additionally used in the treatment of Group 2 patients (n = 22). After 3-month chemotherapy, negative sputum was established in 4 (9.8%) and 6 (14.6%) patients in Groups 1 and 2, respectively. Following 6-month therapy, MBT excretion ceased in 13 (31.7%) and 15 (36.6%) patients in Groups 1 and 2, respectively. After 3- and 6-month therapy, decay cavity closure occurred in 2 (4.8%) and 7 (17%) Group 1 patients and in 4 (9.8%) and 15 (36.6%) Group 2 patients, respectively (p < 0.05).

[Systemic transplantation of autologous mesenchymal stem cells of the bone marrow in the treatment of patients with multidrug-resistant pulmonary tuberculosis].

The study undertaken 3 years ago examined the effect of systemic transplantation of autologous mesenchymal stem cells (MSC) in the complex therapy of 27 patients with pulmonary tuberculosis, including 15 patients with multidrug-resistant pulmonary tuberculosis and 12 with extensive drug resistance of Mycobacterium tuberculosis. All the patients were bacteria-discharging persons with disseminated destructive processes in lung tissue, most (n=17) of them had chronic fibrocavernous tuberculosis. In all the patients, previous long specific antituberculous treatment was ineffective or inadequately effective. After systemic MSC transplantation, 16 patients were followed up for 1.5-2 years or more and the remaining 11 patients for at least 6 months. After MSC administration, a positive clinical effect was observed in all 27 cases; bacterial discharge stopped in 20 patients after 3-4 months; resolution of sustained lung tissue cavities further occurred in 11 patients. At present, a persistent remission of a tuberculous process may be stated in 9 of the 16 patients in whom MSCs were transplanted 1.5-2 years, significant positive bacteriological and morphological changes are observed in 6 patients. Thus, inclusion of transplantation of the autologous MSCs propagated in the culture into a course of antituberculous therapy may be a promising procedure for enhancing the efficiency of therapy in patients with resistant forms of pulmonary tuberculosis.

[Use of fluoroquinolones in the intensive phase of treatment of new tuberculosis cases].

The efficiency of treatment using the routine (I) versus IIB regime was evaluated in 161 new HIV-negative cases of destructive tuberculosis within the first 3 months of chemotherapy. The IIB regimen used in the intensive phase of chemotherapy in new tuberculosis cases before obtaining data on the drug resistance of Mycobacterium tuberculosis significantly enhance the efficiency of treatment in eliminating bacterial excretion and destructive resolution in the lung. The IIB regimen used in new tuberculosis cases with primary multidrug resistance allowed bacterial excretion to be stopped in 80% by month 3 of therapy whereas this index in the similar patients treated by the I regimen was as high as 25%. Decay cavities could be also resolved significantly more frequently by month 6 of therapy in the group of patients treated by the IIB regimen in 59% versus 29% of the patients treated by the I regimen. The inclusion of fluoroquinolones into chemotherapy caused no increase in the incidence of undesirable adverse reactions.

[Diagnostic features and efficiency of treatment in nonbacteria-isolating patients with pulmonary tuberculosis].

In patients with pulmonary tuberculosis with negative sputum bacterioscopic tests, the diagnosis of tuberculosis may be verified by supplementary studies: sputum inoculation, polymerase chain reaction, medium inoculation, bronchoalveolar lavage, smear microscopy, blood medium inoculation, determination of serum antigens and antibodies. The patients in whom sputum Mycobacterium tuberculosis has not been detectable by bacterioscopy, the diagnosis of tuberculosis established by X-ray tomography and verified by supplementary studies should receive chemotherapy (primarily WHO Category 3 chemotherapy). An algorithm is proposed to diagnose tuberculosis in patients with three negative smear microscopic tests.

[Use of valvular bronchoblocation in the complex treatment of patients with disseminated pulmonary tuberculosis complicated by pulmonary hemorrhage].

The results of treatment are analyzed in 102 patients with disseminated pulmonary tuberculosis complicated by pulmonary hemorrhage. The authors have developed and clinically tested a procedure for arresting pulmonary hemorrhage by creating therapeutic hypoventilation and atelectasis of a lung portion, in which there is a source of bleeding, by using valvular bronchoblocation of the draining bronchus. The application of valvular bronchoblocation to patients with pulmonary bleeding enhances the efficiency of complex treatment and reduces mortality by 4.9 times and a need for emergency and urgent surgical interventions by 7.4 times.

[Efficiency of a new standard chemotherapy regimen in the treatment of patients with recurrent pulmonary tuberculosis].

The efficiency of conventional chemotherapy regimens was comparatively studied in 75 patients with recurrent pulmonary tuberculosis. In the patients with recurrent pulmonary tuberculosis, conventional chemotherapy regimen "2b" including isoniazid, rifampicin, pyrazinamide, ethambutol, fluoroquinolone (ofloxacin, ciprofloxacin, and levofloxacin), and canamycin (amikacin) versus conventional chemotherapy regimen "2a" including isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin could cease bacterial isolation after 3-month therapy, as evidenced by sputum microscopy (86.1 and 62.5%, respectively; p < 0.05). Cavity closure was more frequently observed after 6-month chemotherapy using regimen "2b" (76.7 and 48.0%, respectively; p < 0.05). In patients with recurrent pulmonary tuberculosis who isolated Mycobacterium tuberculosis (MBT) resistant to isoniazid and other antituberculous drugs (exclusive of rifampicin), 3-month use of conventional regimen "2b" led to cessation of bacterial isolation (as evidenced by the inoculation test) in 66.7% of cases; but this did not occur with conventional regimen "2a" in any case. Similarly, 3-month use of regimens "2b" and "2a" in patients isolating MBT resistant to rifampicin and other agents (exclusive of isoniazid) resulted in the cessation of bacterial isolation in 80 and 0% of cases, respectively. In multidrug resistance, these parameters were 11.1 and 0%, respectively.

[Artificial pneumoperitoneum in the complex treatment of pulmonary tuberculosis patients isolating drug-resistant mycobacterium tuberculosis].

The pretreated patients who isolated drug-resistant Mycobacterium tuberculosis (MBT) were randomly divided into 2 groups. A multidrug-resistant MBT strain was isolated from 77 and 62.2% of patients in the study and control groups, respectively. Artificial pneumoperitoneum (PP) was applied to the study group patients (n = 95) during adequate chemotherapy. In the control group (n = 43), only chemotherapy was performed in accordance with the data of a MBT drug sensitivity test. The results were assessed by the trend in bacterial isolation cessation and decay cavity closure. In the group of patients treated with PP and chemotherapy, sputum inoculation abacillarity occurred in 72.6 and 95.8% by months 4 and 6, respectively; in the control group, this did in 48.8 and 65.1% in the same periods. Moreover, decay cavity closure was noted in 95.1% in the study group and in 63.7% in the control group following 6 months of treatment.

[Organization of hospital care to patients with tuberculosis concurrent with HIV infection in Tuberculosis care hospital No. seven].

HIV-infection morbidity rates continue to increase in Moscow, the Moscow Region, and in the whole country. The epidemiological situation associated with tuberculosis concurrent with HIV infection remains tense in Moscow and its region, as judged from the data of an analysis of this disease at tuberculosis hospital seven (TH-7) over 9 years. A total of 411 patients with tuberculosis concurrent with HIV infection were treated at TH-7 in 1996 to December 2004. Among them, 49.6% were Moscow residents, 15.1 and 26.5% of the patients lived in the Moscow Region and other regions of the Russian Federation, respectively; 6.8% were homeless persons and 2% foreigners. The number of patients with tuberculosis concurrent with HIV infection has been annually increasing at TH-7. Among the total number of patients, their proportion was 13.4% in 2004. In the structure of patients with comorbidity, the proportion of surgical patients has been on the rise and it was 51.8% in 2004. Among the surgical patients with tuberculosis concurrent with HIV, the proportion of patients with generalized (multiple organ) tuberculosis has increased; it was 50% in 2004. Patients with tuberculosis concurrent with HIV infection need a greater scope of surgical interventions al number of patients for therapeutic and diagnostic purposes.

[Frequency and pattern of adverse reactions due to treatment of patients with pulmonary tuberculosis with antitubercular reserve drugs]. / Chastota i kharakter pobochnykh reaktsii pri lechenii bol'nykh tuberkulezom legkikh protivotuberkuleznymi preparatami rezervnogo riada.

Two hundred and fifty-four patients with pulmonary tuberculosis, treated with reserve antituberculous drugs due to multidrug resistance, the ineffective prior stage of treatment, or intractable adverse reactions, were examined. Aminoglycosides and capreomycin were administered. Combinations simultaneously included 5-7 drugs. Adverse reactions were developed in 72.8% of the patients to different drugs and in different periods. Adverse gastrointestinal, renal, central nervous system, and auditory reactions of reserve drugs were most commonly detected. Essential were also electrolyte metabolic disturbances, hypothyroidism (when reserve drugs were given), intestinal dysbacteriosis, and allergic reactions. The paper analyzes the pattern of adverse reactions caused by each preparation, the time of their occurrence, and methods for their elimination in detail. Adverse reactions to reserve drugs exerted a negative effect of the efficiency of the chemotherapy performed.

[Effectiveness of artificial pneumothorax in the treatment of patients with pulmonary tuberculosis with multiple drug-resistant Mycobacteria]. / Effektivnost' iskusstvennogo pnevmotoraksa v lechenii bol'nykh tuberkulezom legkikh s mnozhestvennoi lekarstvennoi ustoichivost'iu mikobakterii.

The efficiency of treatment was compared in 2 groups of patients with destructive pulmonary tuberculosis and isolation of multidrug resistant Mycobacteria. In 43 patients of a study group, artificial pneumothorax (AP) was used during chemotherapy with reserve drugs while 43 patients of a control group received chemotherapy alone. AP was shown to be highly effective in treating patients with destructive pulmonary tuberculosis who isolated multidrug resistant Mycobacteria. Moreover, by the end of 12-month therapy, AP in combination with chemotherapy ensured cessation of bacterial isolation in 88.7% and cavernous closure in the lung in 86.8%, which was almost twice higher than that with therapy with reserve antituberculous drugs.

[Efficacy of chemotherapy for tuberculosis in patients who isolate drug-resistant strains of M. tuberculosis with different genotypes]. / Effektivnost' khimioterapii tuberkuleza u bol'nykh, vydeliaiushchikh lekarstvenno-ustoichivye shtammy M. tuberculosis s razlichnymi genotipami.

Two hundred and twenty-four patients with pulmonary tuberculosis and bacterial isolation were examined to study the efficiency of chemotherapy in patients who isolated drug-resistant strains of Mycobacterium tuberculosis (MBT) of different genotypes. According to the pattern of susceptibility to antituberculous drugs (ATDs), the patients were divided into 3 groups: 1) those who were found to have ATD-susceptible MBT; 2) those who had multiresistant MBT susceptible to all ATDs, other than isoniazid and rifampicin; 3) those with multidrug resistance. MBT genotyping in accordance with the polymorphism of the length of restriction fragments IS6110 has indicated that the strains of the families W and AI were prevalent in all the groups. However, the strains of mycobacteria of the W family were most frequently (62%) detected among the patients with tuberculosis with slight drug resistance. Treatment was performed in accordance with the data of tests of MBT for their susceptibility to chemical agents. Comparison of the efficiency of therapy failed to reveal any relationship of the genotype of the causative agent within the groups of patients with tuberculosis with different resistance of Mycobacteria, including those with slight drug resistance. At the same time, the pattern of drug susceptibility of MBT largely determined the frequency and trends of bacterial isolation cessation.

[Role of radionuclide studies in the evaluation of the activity of a pathological process in the lymph nodes and lung of patients with tuberculosis]. / Rol' radionuklidnykh issledovanii v otsenke aktivnosti patologicheskogo protsessa v limfaticheskikh uzlakh i legkikh u bol'nykh tuberkulezom.

The authors studied the activity of a pathological process in the lymph nodes of the mediastinum, by using 67Ga citrate and 99mTc, and pulmonary circulation with MAA-99mTc. Radionuclide studies have established that in new cases of respiratory tuberculosis, the function of lymph nodes recovers by 1.5 times higher than that in pretreated patients. In patients with destructive tuberculosis, pulmonary circulation restores insignificantly and slowly, particularly in a group of pretreated patients. This is explained by the fact that the lung fibrous changes available prior to therapy defy an evolutionary process.

[Course of tuberculosis in patients with HIV infection]. / Techenie tuberkuleza u bol'nykh s VICh-infektsiei.

AIM: To evaluate clinical features of tuberculosis in correlation with HIV-infection duration. MATERIAL AND METHODS: 117 patients with HIV-infection were divided into three groups: HIV-infected in the presence of long-standing tuberculosis (group 1), HIV- and tuberculosis-infected simultaneously (group 2), tuberculosis-infected 5-10 years after getting HIV-infection. CONCLUSION: Clinical picture and course of tuberculous infection in HIV-infected patients depend on the time of getting HIV-infection and are determined by the severity of T-cell immunodeficiency. RESULTS: Tuberculosis runs its usual course in patients of groups 1 and 2. In group 3 tuberculosis ran atypically, had lethal outcome due to either tuberculosis or opportunistic infections.

[Efficacy of treatment for pulmonary tuberculosis with multidrug mycobacterial resistance]. / Effektivnost' lecheniia tuberkuleza legkikh, vyzvannogo mikobakteriiami s mnozhestvennoi lekarstvennoi ustoichivost'iu.

The efficiency of treatment was studied in 149 patients with pulmonary tuberculosis who isolated multidrug resistance of Mycobacteria tuberculosis (MBT). The multidrug resistance of MTB, to at least isoniazid and rifampicin can be associated with both the resistance to other essential (streptomycin, ethambutol) and that to reserve drugs. With this, patients with MBT resistance to a combination of essential and reserve drugs more frequently showed a chronic course of the disease with severe clinical manifestations and more disseminated infiltrative-and-destructive lesions in the lung. Drug treatment regimens using a combination of reserve drug were effective only in patients with MBT resistance to essential drugs while they were little effective in those with resistance to essential and reserve agents. The use of artificial pneumothorax in patients with MBT resistance to essential and reserve agents could cease bacterial isolation in 77.8% of the patients even by ingesting a small number of the drugs. Clinically, the occurrence of MBT resistance to reserve drugs is justified to determine a radically new status in patients in the context of chemotherapy and the whole further treatment in this group of patients. A clinical classification of MBT multidrug resistance is proposed, which identifies two categories of patients with pulmonary tuberculosis: those resistant to essential drugs and those resistant to a combination of essential and reserve drugs.

[Dynamics in microcirculation and regional ventilation of the lung during treatment in patients with destructive tuberculosis]. / Dinamika mikrotsirkuliatsiimi regional'noi ventiliatsii legkikh v protsesse lecheniia u bol'nykh destruktivnym tuberkulezom.

Studies of the time course of changes in regional blood flow and regional ventilation of the lung in patients with destructive pulmonary tuberculosis (DPT) suggest that there may be different shifts in radionuclide indices after antibacterial therapy. Full recovery of regional blood flow and regional ventilation of the lung sometimes is accounted for by the resolution of inflammatory changes, by the healing of destruction frequently attended by a significant improvement, but there is a more regular change in the areas of the underlying process in particular, through evolving pneumosclerosis. A comprehensive radionuclide study in patients with destructive pulmonary tuberculosis in combination with clinical and X-ray studies allows clinicians to investigate the extent and site of a pathological process and thereby to define the functional status of capillary blood flow and pulmonary alveoles. Radionuclide studies enable a trend of a pathological process in the lung to be defined during treatment since alterations in the lung reflect the time course of changes in a specific process and the efficiency of treatment.

[Effectiveness of the standard mode of chemotherapy for newly-diagnosed patients with destructive pulmonary tuberculosis with bacterial isolation]. / Effektivnost' standartnogo rezhima khimioterapii pri lechenii vpervye vyiavlennykh bol'nykh destruktivnym tuberkulezom legkikh s bakteriovydeleniem.

The authors evaluated the efficiency of a routine drug therapy regimen by the WHO category 1 in treating 149 new cases of destructive pulmonary tuberculosis and bacterial isolation. They used not only the WHO sputum smear negativization criterion, but the data of cultural studies and on lung cavernous closure. The specific features of the approach applied were compulsory cultural studies determining Mycobacterium sensitivities before treatment and compulsory correction of chemotherapy after there was evidence for the sensitivity. Retrospective analysis of 6-month chemotherapy has ascertained that the efficiency of the routine drug therapy regimen largely depends on the baseline extent of infiltrative and destructive changes in the lung and on the baseline resistance of Mycobacteria tuberculosis. They showed a high baseline resistance to streptomycin (20.6%) and streptomycin and isoniazid (33.1%) and a low baseline resistance to ethambutol (5.1%). In these cases, the more optimum regimen was a combination of rifampicin, pyrazanamide, and ethambutol. When Mycobacteria showed multidrug resistance, the routine regimen was ineffective and caused amplification to a larger number of drugs. A modified treatment course using the routine regimen in the intensive phase was developed. If Mycobacterial resistance was present, compulsory correction was made by using reserve agents, pathogenetic treatments, artificial pneumothorax or surgical interventions, which made it possible to abacillate 94.1% of patients by their smears and culture by months 4-5 and to close caverns in 91.3% of cases by months 8-10.