Availability of drugs and resistance testing for BPaLM regimen for rifampicin-resistant tuberculosis in Europe.

OBJECTIVES: Multidrug-resistant/Rifampicin-resistant tuberculosis (TB) is a major obstacle to successful TB control. The recommendation by the World Health Organization to use bedaquiline, pretomanid, linezolid and moxifloxacin (BPaL(M)) for 6 months, based on results of three trials with high efficacy and low toxicity, has revolutionized treatment options. METHODS: In this study, representatives of the Tuberculosis Network European Trialsgroup (TBnet) in 44/54 countries of the WHO Europe region document the availability of the medicines and drug susceptibility testing (DST) of the BPaL(M) regimen through a structured questionnaire between September to November 2023. RESULTS: 24/44 (54.5%), 42/44 (95.5%), 43/44 (97.7%), and 43/44 (97.7%) had access to pretomanid, bedaquiline, linezolid, and moxifloxacin, respectively. Overall, 23/44 (52.3%) had access to all the drugs composing the BPaL(M) regimen. 7/44 (15.9%), 28/44 (63.6%), 34/44 (77.3%) and 36/44 (81.8%) had access to DST for pretomanid, bedaquiline, linezolid and moxifloxacin, respectively. DST was available for all medicines composing the BPaL(M) regimen in 6/44 (13.6%) countries. CONCLUSION: Only in about half of the countries participating in the survey clinicians have access to all the BPaL(M) regimen drugs. In less than a fifth of countries, a complete DST is possible. Rapid scale up of DST capacity to prevent unnoticed spread of drug resistance and equal access to new regimens are urgently needed in Europe.

Endobronchial Primary Pulmonary Angiomatoid Fibrous Histiocytoma in a Patient with Testicular Germ Cell Tumor: An Evidence Against Somatic Transformation.

Primary Pulmonary Angiomatoid Fibrous Histiocytoma is a recently described soft tissue tumor with challenging differential diagnosis both clinically and pathologically due to its rarity in this location. It may also occur as a secondary malignancy and its occurrence either as a somatic malignancy arising in the germ cell tumor or as a secondary malignancy after chemotherapy is questionable. In this report, we present a 29-year-old male patient with a mass in the lower lobe of the left lung, who underwent orchiectomy and received adjuvant chemotherapy due to a mixed germ cell tumor 8 years ago. Morphology, immunophenotype, and molecular findings were consistent with the diagnosis of primary pulmonary angiomatoid fibrous histiocytoma. Fluorescent in situ hybridization was unable to demonstrate the presence of 12p amplification or isochromosome 12p, which is known as the key event in the development of testicular germ cell neoplasia even present in somatic malignancies arising in germ cell tumors. Our results support that angiomatoid fibrous histiocytoma arising as a secondary malignancy does not represent the somatic transformation of germ cell tumors.

[Mycobacterium abscessus infection management: Macrolide and quinolone desensitization]. / Mycobacterium abscessus enfeksiyonu yönetimi: Makrolid ve kinolon desensitizasyonu.

Antibiotic hypersensitivity reactions can lead to marked morbidity, mortality and inadequate treatment options. Mycobacterium abscessus infection is a difficult management system for clinicians since it most commonly involves the lungs, progresses if untreated, and the organism is resistant to many antibiotics, as well as the agents used in treatment can cause undesirable side effects. Although macrolides are one of the most reliable antibiotic groups in terms of allergic reactions, early type hypersensitivity reactions against macrolides, one of the main antibiotics used in the treatment of Mycobacterium abscessus lung disease, may make the treatment management of the disease difficult. Due to the rapid increase in the use of quinolone in recent years, the frequency of developing allergic reactions with these agents also increases. In cases where antibiotic hypersensitivity is detected, the use of the responsible agent should be avoided, but desensitization may be necessary in cases without different treatment options. In this study, it was aimed to present a case of successful desensitization with clarithromycin and moxifloxacin in a patient who was diagnosed with Mycobacterium abscessus lung disease and developed anaphylaxis with clarithromycin and moxifloxacin after treatment was initiated.

[Frequently Isolated Slow Growing Nontuberculous Mycobacteria from Pulmonary Samples and Evaluation of Drug Susceptibility Testing Results in a Referral Hospital in Turkey]. / Türkiye'de Bir Referans Hastanede Akciger Örneklerinden Siklikla Izole Edilen Yavas Üreyen Tüberküloz Disi Mikobakteriler ve Ilaç Duyarlilik Sonuçlarinin Degerlendirilmesi.

Most of the nontuberculous mycobacteria (NTM) are opportunistic pathogenic microorganisms and free-living in nature. NTM can cause a wide range of infections. However, pulmonary NTM disease is the most frequent clinical picture. The aim of this study was to identify and evaluate drug susceptibility of slow growing NTM isolated from pulmonary samples of patients prediagnosed as tuberculosis between 2014 and 2018 in Atatürk Chest Diseases and Chest Surgery Training and Research Hospital Microbiology Laboratory by a commercial microtube dilution plaque method. A total of 435 NTM strains obtained from suspected TB patients were included in the study. After the samples were processed by homogenization and decontamination and acid-fast staining, culture in two solid media (Löwenstein-Jensen, Ogawa) and in MGIT-BACTEC960 automated system were performed. Acid-fast bacilli isolated from culture media were identified by using cart test (MPB64, Capilla TB-Neo) and polymerase chain reaction (PCR) based reverse hybridization "line probe assay (LPA)" method (GenoType MycobacteriumCM/AS, Hain Lifescience, GmbH, Germany). After DNA isolation from the culture, PCR was performed by using the primers specific for mycobacterial 23S rRNA spacer region. PCR products were then hybridized with the probes specific for Mycobacterium species on nitrocellulose strips according to the recommendations of the manufacturer and the results were evaluated. In this study, Mycobacterium avium (n= 77, 17.7%), Mycobacterium intracellulare (n= 70, 16.1%), Mycobacterium szulgai (n= 19, 4.4%), Mycobacterium kansasii (n= 10, 2.3%) ve Mycobacterium smiae (n= 9, 2.1%) were isolated as slowly growing mycobacteria from the pulmonary patients. Susceptibility testing was performed in cation-adjusted Mueller-Hinton broth (CAMH), supplemented with "oleic acid, albumin dextrose catalase" according to CLSI/ M24-A2 guideline recommendations. For the antibiotic susceptibility test, ready-to-use plaque drugs for slow-growing mycobacteria (SLOMYCO-Sensititre, TREK Diagnostic Systems Ltd, UK), were used. M.intracellulare, M.avium, M.kansasii and M.smiae isolates were found to be sensitive to clarithromycin %100, %99, %100 and %100, respectively. For M.intracellulare and M.avium isolates, moxifloxacin and linezolid sensitivity values were found to be 91%, 64% and 80%, 74% respectively. M.kansasii isolates were more sensitive than M.simiae isolates to the most of the drugs. M.kansasii isolates, were susceptible to rifabutin, rifampin, moxifloxacin, amikacin, linezolid, trimethoprim-sulfamethoxazole (TMP-SMX), ciprofloxacin and etambutol, with the frequencies of 100%, 90%, 100%, 100%, 80%, 70% and 50%, respectively. The study showed that the species identification and drug susceptibility testing of frequently isolated slow-growing NTM's from pulmonary specimens could guide for the treatment.

Comparison of the International Classification of High-resolution Computed Tomography for occupational and environmental respiratory diseases with the International Labor Organization International Classification of Radiographs of Pneumoconiosis.

The International Classification of High-resolution Computed Tomography for Occupational and Environmental Respiratory Diseases (ICOERD) has been developed for screening and diagnosis of occupational lung diseases. We evaluated the association of icoerd with the International Labor Organization (ILO) classification and respiratory functions in pneumoconiosis. Chest x-rays of patients with pneumoconiosis were classified with ilo and icoerd using hrct, irregular opacity, pleural pathology, and emphysema was detected in 78, 19, and 53 patients, and using chest x-rays in 47, 4, and 14 patients, respectively. There was a significant correlation between ILO categories and ICOERD grades. There was a negative correlation between ILO categories and FEV1% and FVC%, whereas, ICOERD grades were not correlated with FEV1% and FVC%. HRCT was superior to chest x-rays to detect pneumoconiosis in early stage, but not in evaluating pulmonary functions.

[Tuberculosis Laboratory Surveillance Network (TuLSA) study group. The first step for national tuberculosis laboratory surveillance: Ankara, 2011]. / Ulusal Tüberküloz Laboratuvar Sürveyansina ilk adim: Ankara, 2011.

The most effective method for monitoring country-level drug resistance frequency and to implement the necessary control measures is the establishment of a laboratory-based surveillance system. The aim of this study was to summarize the follow up trend of the drug-resistant tuberculosis (TB) cases, determine the load of resistance and evaluate the capacities of laboratories depending on laboratory quality assurance system for the installation work of National Tuberculosis Laboratory Surveillance Network (TuLSA) which has started in Ankara in 2011. TuLSA studies was carried out under the coordination of National Tuberculosis Reference Laboratory (NRL) with the participation of TB laboratories and dispensaries. Specimens of TB patients, reported from health institutions, were followed in TB laboratories, and the epidemiological information was collected from the dispensaries. One isolate per patient with the drug susceptibility test (DST) results were sent to NRL from TB laboratories and in NRL the isolates were rechecked with the genotypical (MTBDRplus, Hain Lifescience, Germany) and phenotypical (MGIT 960, BD, USA) DST methods. Molecular epidemiological analysis were also performed by spoligotyping and MIRU/VNTR. Second-line DST was applied to the isolates resistant to rifampin. A total of 1276 patients were reported between January 1st to December 31th 2011, and 335 cases were defined as "pulmonary TB from Ankara province". The mean age of those patients was 43.4 ± 20 years, and 67.5% were male. Three hundred seventeen (94.6%) patients were identified as new cases. The average sample number obtained from pulmonary TB cases was 3.26 ± 2.88, and 229 (68.3%) of them was culture positive. DST was applied to all culture positive isolates; 90.4% (207/229) of cases were susceptible to the five drugs tested (ethambutol, isoniazid, pyrazinamide, rifampicin, streptomycin). Eight (3.5%) of the isolates were multidrug-resistant (MDR-TB), while no extensively drug-resistant strains were detected. MDR-TB is likely to occur in 63.3 times more among previously treated cases, and 73.3 times more in legal aliens. The achievement of therapy among pulmonary TB cases was 91.9%. Spoligotyping performed for 221 M.tuberculosis complex isolates, showed that all strains were clustered in nine groups. SIT 41 (105/221; 47.5%) was the most frequent spoligotype detected, and clustering rate based on MIRU-VNTR results were found as 16.3%. All of the clustered strains were sensitive while all of MDR-TB isolates showed specific MIRU-VNTR profiles. In conclusion, TuLSA studies started in Ankara in 2011 and the system is still expanding in the country. Our data obtained with TuLSA have been published as a regional surveillance data in the WHO Global Tuberculosis Report 2011, and as a national surveillance data in Global Tuberculosis Report 2012.

Immediate-type hypersensitivity reactions due to antituberculosis drugs: a successful readministration protocol.

BACKGROUND: Little is known about drug hypersensitivity reactions from antituberculosis drugs. OBJECTIVE: To determine the frequency, risk factors, and characteristics of immediate-type hypersensitivity reactions from first-line antituberculosis drugs and to evaluate the usefulness of a readministration protocol for culprit drugs in this group of patients. METHODS: The study population consisted of patients with tuberculosis who were hospitalized and treated in the authors' hospital in 2011. Demographics and disease and treatment characteristics of patients with immediate-type hypersensitivity from antituberculosis drugs were compared with the other patients. Culprit drugs were readministered gradually according to a defined protocol to patients with immediate-type hypersensitivity. RESULTS: Tree hundred seventy-nine patients were included in the study. Eighteen immediate-type hypersensitivity reactions were detected in 13 patients (3.43%). The only identified risk factor was female sex (odds ratio 4.085). Isoniazid, rifampicin, pyrazinamide, and ethambutol were readministered in 11 patients and rifampicin was readministered in 2 patients, with 6- to 8-step protocols for each drug. Only in 2 patients did allergic reactions with rifampicin develop during the procedure. In these patients, after treatment and complete remission of allergic symptoms, the last tolerated dose was administered and the protocol was completed with the same adjustments. CONCLUSION: Immediate-type allergic reactions from antituberculosis drugs are not rare and not related to disease or treatment characteristics. The protocols used in this study provide a useful and safe method for readministration of culprit drugs to patients with antituberculosis drug hypersensitivity.

Intrathoracic Castleman disease.

AIM: To analyze patients with Castleman disease who were diagnosed by surgery. MATERIALS AND METHODS: We retrospectively investigated the postoperative pathological records of operations performed between January 1992 and December 2012 in our hospital. Files of 19 patients with the diagnosis of Castleman disease were analyzed. RESULTS: There were 13 male and 6 female patients with a mean age of 40.1 + 11.4 (range: 20-57) years. Fifteen thoracotomies and 3 video-assisted thoracoscopies, 12 on the right side and 6 on the left side, and 1 mediastinoscopy were performed. Biopsies and mass excisions were performed in 2 and 17 cases, respectively. Histopathological findings were hyaline vascular-type (n = 16), plasma cellular- type (n = 2), and hyaline vascular plus plasma cellular-type (n = 1) Castleman disease. CONCLUSION: Castleman disease can occur in all areas of the thorax, but the mediastinum and hilum are the most common locations. Surgical excision is the best method of diagnosis and treatment. Complete excision is curative for local forms of the disease. However, complete excision may not be possible at all times due to local invasion and hypervascularization. Multimodal treatment, including chemotherapy, is recommended in patients with a multicentric form of the disease, and they should be followed closely.

Tuberculosis preventive treatment in a single medical center and evaluation of the results.

The aim of the present study was to evaluate the application of tuberculosis preventive treatment (TB-PT). Demographic data, indications and results for cases that received TB-PT at the Ankara Tuberculosis Control Dispensary No. 7 between 2008 and 2011 were retrospectively evaluated. The 'Prevention with Drugs' registry at the dispensary was used. A total of 463 cases received TB-PT, with the indications including close contact with an active TB case (44%), positive tuberculin skin test (TST) in a child <15 years-old (25%) and immunosuppressive therapy (31%). The immunosuppressed group (n=144) were administered steroids (10%) or tumor necrosis factor (TNF)-α inhibitors (90%). Indications of TST conversion and sequela lesions were not observed among the cases. The male/female ratio was 106/98 for cases with TB close contact, 61/54 for TST-positive cases and 85/59 for immunosuppressed cases. The mean ages of these groups were 9±5.7, 9.5±3.8 and 38±14.9 years, respectively. TB-PT was completed in 364 cases (78.6%), and the rate of discontinuation due to adverse effects was 1% for TB close contact and 2% for TST-positive cases, but 5% for immunosuppressed cases. While the percentage of TB close contact cases receiving TB-PT decreased during the four-year study period, the percentage of cases with immunosuppression (in particular patients using TNF-α inhibitors) increased. Among the studied cases, only two subjects developed active TB. The first case involved a 1.5-year-old female that had close contact exposure to TB from a parent, while the other case involved a 14-year-old TST-positive male (induration size,16 mm). In conclusion, patients receiving TB-PT should be monitored and/or followed-up carefully to control any side-effects from the treatment and development of active TB.

[The relation of serum interleukin-2 and C-reactive protein levels with clinical and radiological findings in patients with pulmonary tuberculosis]. / Akciger tüberkülozlu hastalarda serum interlökin-2 ve C-reaktif protein düzeylerinin klinik ve radyolojik bulgularla iliskisi.

Immunological events, not the bacilli, are responsible from the tissue damage of tuberculosis. Clarifying the immunological events may lead to the development of new approaches to treatment and defence against tuberculosis disease. In this study we aimed to determine the serum levels of interleukin-2 (IL-2) and C-reactive protein (CRP) in patients with tuberculosis and evaluate the relationship with clinical and radiological findings. The study included 60 patients (mean age: 37 +/- 12 years, all male) with newly diagnosed pulmonary tuberculosis and 23 healthy controls (mean age: 40 +/- 13 years, all male). Admission symptoms, clinical features, demographic data, laboratory investigations and radiological findings were all recorded into the study form. Serum samples which were obtained for determination of IL-2 and CRP levels were preserved at -80 degrees C. While serum IL-2 levels were similar in patients with tuberculosis and healthy controls, serum CRP levels were significantly higher in patients with tuberculosis (p< 0.001). There was a positive correlation between serum IL-2 level and the diameter of cavity (p= 0.012). CRP levels were significantly higher in patients who admitted with fever (p= 0.001) and weight loss (p= 0.024). Serum CRP levels were significantly higher in patients who had involvement of four or more zones (p= 0.029) and multiple cavitary disease (p= 0.001). There was a positive correlation between serum CRP level and the diameter of cavity (p= 0.004). In conclusion, apart from the diameter of cavity, serum IL-2 levels were not correlated with any clinical, laboratory or radiological parameter. Serum CRP levels were a good indicator of disease severity.

Bronchoscopic diagnosis of ruptured pulmonary hydatid cyst presenting as nonresolving pneumonia: report of two patients.

The diagnosis and management of pulmonary hydatid disease represents an important clinical problem in areas of the world endemic to echinococcal infection. We report two patients, ages 14 and 34, respectively, who were admitted to our clinic for investigation of nonresolving pneumonia. Neither had responded to antibiotics prior to admission. Chest x-rays demonstrated lobar collapse and consolidation in both patients. Fiberoptic bronchoscopy revealed laminated membrane of hydatid cyst occluding the bronchus of apicoposterior and anterior segmental bronchi of the left upper lobe in the first patient and the anterior segment of the right upper lobe in the second patient. The diagnoses were confirmed at the time of surgery.

The effect of mannose-binding protein gene polymorphisms in recurrent respiratory system infections in children and lung tuberculosis.

Mannose-binding lectin (MBL) is able to bind pathogens as an opsonin and plays an important role in the innate immunity. The aim of the present study was to determine the frequencies of the MBL gene variants in the Turkish population and to examine the presence of any association between MBL variants and development of tuberculosis (TB) in adults and recurrent respiratory tract infections in children. Two structural gene mutations in exon 1 of MBL gene (codon 54 and codon 57) were studied. The overall distribution of genotypes did not significantly differ between controls and TB patients/children with recurrent respiratory system infections. The frequency of allele B was calculated as 0.14, 0.09 and 0.06 for control, TB patients and children with recurrent respiratory system infections, respectively. It was found to be significantly lower in children with recurrent respiratory system infections than in controls (chi2: 4.68, d.f: 1, p: 0.030).