Investigation of Epidemiological Characteristics and Molecular Mechanisms of Moxifloxacin Resistance in Mycobacterium tuberculosis Strains Isolated from Pulmonary Tuberculosis Patients.

TEZ10802Tez (Uzmanlık) -- Çukurova Üniversitesi, Adana, 2015.Kaynakça (s. 62-65) var.ix, 66 s. : res. (bzs. rnk.), tablo ; 29 cm.Amaç: Bu çalışmada bölgemizdeki klinik materyallerden izole edilen Mycobacterium tuberculosis suşlarının moksifloksasin duyarlılıklarının fenotipik yöntemlerle tespit edilmesi ve bölgesel direnç oranlarının belirlenmesi ayrıca fenotipik direnç ile gyrA genindeki mutasyonların ilişkisinin araştırılması amaçlandı. Gereç ve Yöntem: Çalışmaya Adana Bölge Tüberküloz Laboratuvarına gönderilen pulmoner tüberkülozlu hasta örneklerinden izole edilen Mycobacterium tuberculosis suşlarından çoklu ilaç direnci görülmeyen sıralı 100 izolat ile çoklu ilaç direnci tespit edilen 37 izolat dahil edilmiştir. Bu izolatların Löwenstein-Jensen proporsiyon yöntemi kullanılarak moksifloksasin’e duyarlılıkları belirlenmiş ve epidemiyolojik özellikleri araştırılmıştır. Yine bu izolatların gyrA bölgesinin dizi analizi yapılmış ve ilaç duyarlılık oranları ile karşılaştırılmıştır. Bulgular: Fenotipik duyarlılıkları test edilen 137 izolatın 25’inde (% 18,2) moksifloksasine karşı direnç bulunmuştur. Çoklu ilaç direnci görülmeyen ve çoklu ilaç direnci görülen suşlar arasındaki direnç oranları sırasıyla % 17 ve % 21,6 olarak tespit edilmiştir. 25 dirençli klinik izolatın gönderildiği bölgelere göre dağılımına baktığımızda; izolatlardan 10’unun Adana, 6’sının Gaziantep, 5’inin Hatay, 3’ünün Mersin ve 1’inin de Kahramanmaraş iline ait oldukları tespit edilmiştir. Çalışmaya dahil edilen tüm izolatların gyrA bölgesinin dizi analizi sonucuna göre toplamda 6 örnekte tek baz mutasyonuna rastlanmıştır. Mutasyonların pozisyonları Asp94Tyr, Asp94Gly, Ala90Val, Gly88Ala ve iki örnekte de Asp89Asn şeklinde tespit edilmiştir. Mutasyon görülen örneklerin ikisi moksifloksasine fenotipik olarak duyarlı bulunmuştur. Sonuç: Çalışmamız sonucunda moksifloksasine karşı gelişen direncin tüberküloz tedavisine sekonder olamayacağı tespit edilmiştir. Oluşan direnç ile genin analiz edilen kısmındaki mutasyonların ilişkisinin yetersiz olduğu ve yüksek dirençten farklı moleküler mekanizmaların sorumlu olacağı görülmüştür. Moksifloksasin direncinin araştırılmasının daha geniş vaka grupları ve izolatlar kullanılarak devam ettirilmesi ayrıca bu grup ilaçlara karşı kısa sürede direnç gelişme ihtimalinin varlığı ve non-spesifik endikasyonlarda daha sınırlı kullanılması gerektiğinin ısrarla anlatılmasının önemli olacağı sonucuna varılmıştır.Objective: In this study, it is aimed to determine the moxifloxacin sensitivities of Mycobacterium tuberculosis strains isolated in our region and to specify the regional resistance rates besides to investigate the relation of phenotypical resistance with mutations in gyrA gene. Materials and Method: Sequential 100 isolates that are seen to be non-multi drug resistant and 37 isolates that are determined as multidrug resistant among Mycobacterium tuberculosis strains isolated from pulmonary tuberculosis patient's samples which sent to Region Tuberculosis Laboratory of Adana were included in this study. Drug sensitivity rates and DNA Sequencing of gyrA region of these isolates are compared again. Findings: Resistance to moxifloxacin is found in 25 of 137 (18,2 %) isolates of which phenotypic susceptibilities were tested. Resistance rates among strains which seen to have multidrug resistance and those which have not multidrug resistance were 17 % and 21,6 % respectively. Looking at the distribution according to regions which sent 25 clinical isolates; it is determined that 10 of isolates were belonged to Adana, 6 to Gaziantep, 5 to Hatay, 3 to Mersin and 1 to Kahramanmaraş province. Among all isolates included in study, Single bases mutation was encountered in 6 samples in total according to DNA sequencing result of gyrA region. The positions of mutations were identified as Asp94Tyr, Asp94Gly, Ala90Val, Gly88Ala and in 2 samples as Asp89Asn. Two of the samples which mutation is seen were found to be sensitive to moxifloxacin phenotypically. Result: At the end of our study it is determined that, resistance developed to moxifloxacin would not be secondary in the treatment of tuberculosis. It is seen that different molecular mechanisms will be responsible from high resistance and the relation between resistance and mutations in the analysed gene is insufficient. It is concluded that research on moxifloxacin resistance should be continue with wider case groups and isolates also it will be important to persistently explain that there is a probability of resistance development in a short time to these group of drugs and it is required to use them more limited in non-spesific indications.Bu çalışma Ç.Ü. Bilimsel Araştırma Projeleri Birimi tarafından desteklenmiştir. Proje No: TF2013LTP12

Normal Microbial Flora effect on Human Health and Human Microbiome Project

Presence of microorganisms that we share our body has been an already known fact. However, changes in our way of life and particularly new molecular compounds we encounter, cause several effects on microorganisms. Recently developed new generation sequencing techniques, allow detailed analysis of the changes in these microbial communities. Recent studies indicate that, these communities of microorganisms have more impact than predicted on human health. [Archives Medical Review Journal 2014; 23(3.000): 420-423

Detection and Molecular Analysis of Moxifloxacin MIC Values of Mycobacterium tuberculosis Strains Isolated from Clinical Specimens

WOS: 000476627600001PubMed ID: 31414626Tuberculosis (TB) is a chronic, granulomatous and necrotizing disease caused by microorganisms belonging to the Mycobacterium tuberculosis complex group. In 2017, 6.4 million new TB cases have been reported according to the World Health Organization 2018 Global Tuberculosis Report. TB remains among the major health problems of our time due to the increasing drug resistance problem and the difficulties in definitive diagnosis in recent years. It is stated by clinicians that intensive use of quinolone group drugs with oral form in simple indications such as respiratory or urinary tract infections may lead to resistance and this may result in treatment failures. The aim of this study was to determine the moxifloxacin susceptibility of M. tuberculosis isolates obtained from clinical specimens by phenotypical methods, to determine the resistance rates of moxifloxacin and to investigate the relationship between phenotypical resistance and mutations in the gyrA gene. A hundred (n= 100) consecutive non-multidrug resistant and 37 non-consecutive multidrug resistant M.tuberculosis strains isolated from the clinical specimens of patients with pulmonary tuberculosis were included in the study. The moxifloxacin susceptibility of the isolates was determined by using Lowenstein-Jensen medium and their epidemiological properties were investigated and also mutations detected by gyrA region were compared with drug susceptibility rates. Of the 137 isolates tested for phenotypical susceptibility, 25 (18.2%) were found to be resistant to moxifloxacin. Resistance rate among non-multidrug resistant and multidrug resistant isolates were determined as 17% and 21.6%, respectively. According to the results of the sequencing analysis, of the gyrA regions of all the isolates included in the study, a single base mutation was found in a total of six samples. The location positions of the mutations were determined as D94Y, D94G, A90V, G88A and among two strains as D89N. Two of the isolates with mutations were found to be phenotypically susceptible to moxifloxacin. In our study, it was found that moxifloxacin resistance in M.tuberculosis isolates was higher than similar studies and it was found that different mechanisms may be responsible for the existing resistance other than the mutations in the gyrA gene. It was concluded that the data obtained from the study should be shared with all clinicians in the country due to the possibility of resistance development to this group of drugs in a short time and considering this drug will have an important role in the treatment of TB, it should be used more limited in non-specific indications. Further studies using larger case groups and isolates are needed for the continuation of the research

A Case with Microbiologically Confirmed Lepromatous Leprosy from Mersin, Türkiye

Leprosy, a chronic infectious disease caused by Mycobacterium leprae bacillus, causes damage especially to the skin, upper respiratory tract mucosa and peripheral nerves. In order to prevent the spread of leprosy, which has an effective treatment, it is essential to promptly identify and accurately diagnose cases in the early stages. In this article, we present a patient with lepromatous leprosy who applied to the dermatology outpatient clinic in a non-endemic region. The diagnosis was confirmed through the detection of acid-fast bacilli in the patient’s skin biopsies and the identification of the M. leprae complex using molecular methods. This disease, characterized by non-specific skin lesions in the early stages, should be considered by all clinicians as a potential differential diagnosis. Furthermore, adopting a multidisciplinary approach can greatly facilitate the diagnosis process

Pulmonary Brucellosis Case Report

Bruselloz; ülkemizde endemik olarak görülen, tekrarlayan ateş, eklem ağrısı, halsizlik, iştahsızlık ile seyreden sistemik bir hastalıktır. Solunum sistemi tutulumunda en sık görülen semptom %10-33 ile non prodüktif öksürüktür. Olgumuz, 76 yaşında, erkek hasta kırsal bölgede çiftçilik ile uğraşıyor. On beş gündür devam eden kuru öksürük, üşüme-titreme ile yükselen ateş ve uykuya eğilim şikayetleri ile enfeksiyon hastalıkları servisine yatışı yapıldı. Özgeçmişinde taze peynir tüketimi mevcuttu. Hastaya ampirik sefrtriakson 2x2 gr ve klindamisin 4x600 mg IV başlandı. Brusella agglutinasyonu 1/160 titrede pozitif olarak saptandı. Doksisiklin 2x100 mg ve rifampisin 2x300 mg başlandı. Toraks bilgisayarlı tomografisinde (BT) pnömoni, solda minimal plevral efüzyon izlendi. Pnömoni etkenleri serolojik olarak dışlandı. Bruselloz tedavisinin 5. gününde hastanın ateşi düştü, genel durumu düzeldi ve akciğer dinleme bulgularında düzelme görüldü. Kan kültüründe Brucella melitensis üremesi oldu. Tedavisi 8 haftaya tamamlanan hastada klinik ve radyolojik olarak düzelme görüldü. Ülkemizde endemik olarak görülen brusellozun nadir görülen pulmoner tutulumu, pnömoni ile başvuran hastalarda ayırıcı tanıda akılda tutulmalıdırBrucellosis, an endemic disease in our country, is a systemic disorder characterized with recurrent fever, joint pain, malaise and anorexia. Although it may affect many systems, respiratory involvement is quite rare. In case of respiratory system involvement, the most common (10-33%) symptom is non-productive cough. Our patient was a 76 year old male living in rural areas engaged in farming. He was hospitalized with fifteen days ongoing complaints, dry cough, fever with chills and tendency to sleep. On physical examination, fever, tachypnea, decreased breath sounds at left lung baseline and crepitan crackles at right baseline and loss of muscle strength was present. In his history, fresh cheese consumption was present. Empirically, ceftriaxone and clindamycin was initiated. Brucella agglutination was 1/160 titer positive. Doxycycline and rifampin was started. Thoracic computed tomography revealed pneumonia and minimal pleural effusion on the left lobe. The other pneumonia agents were excluded serologically. Cerebrospinal fluid revealed normal findings. Neurobrucellosis was excluded. On the fifth day of brucellosis treatment patient was afebrile, general condition improved and lung symptomsand findings resolved. Blood culture was positive for Brucella melitensis. The patient completed 8 weeks of treatment, clinical and radiological improvement was seen. Brucellosis, an endemic disease in our country, rarely shows pulmonary involvement and it should be kept in mind in differential diagnosis in patients admitted with pneumoni