Investigation of Extensive Drug Resistance in Multidrug Resistance Tuberculosis Isolates

Abstract

Increasing number of drug resistant tuberculosis (TB) cases, observed in recent years, is an important public health problem. Extensively drug resistant TB (XDR-TB) is the development of resistance against any fluoroquinolones and at least one of the injectable second line anti-TB drugs in addition to resistance against isoniazide and rifampicin which are the first line anti-TB drugs [definition of multidrug resistant TB (MDR-TB)]. Anti-TB therapy failed with first-line anti-TB drugs due to MDR-TB cases is being planned according to second-line anti-TB drug susceptibility test results if available and if not, standart treatment protocols are used. Although it is recommended that individual anti-TB therapy should be designed according to the isolate's susceptibility test results, standart therapeutic protocols are always needed since second-line anti-TB drug susceptibility testing generally could not be performed in developing countries like Turkey. For this reason, nationwide and regional surveillance studies to determine the resistance patterns are always needed to make decisions about the standard therapy algorithms. In this study, it was aimed to investigate the presence of extensive drug resistance among 81 MDR-TB isolates obtained from various health care facilities from Istanbul, Izmir and Manisa and to determine the XDR-TB incidence in Marmara and Aegean regions. Furthermore, we aimed to provide epidemiological data to clinicians to support their choice of second-line anti-TB drugs for MDR-TB infections. Susceptibility testing of isolates for the first and the second-line anti-TB drugs were performed by using modified Middlebrook 7H9 broth in fluorometric BACTEC MGIT 960 system (Becton Dickinson, USA). Eighty-one MDR-TB isolates included in this study were isolated from 43 (53.1%) patients residing in Istanbul, 26 (32.1%) in Izmir and 12 (14.8%) in Manisa provinces. We could not find any isolate consistent with XDR-TB definition in this study. Second-line drug resistance rates of MDR-TB isolates to amikacin and kanamycin were 1.2%, ofloxacin and levofloxacin were 2.5%, capreomycin was 14.8%, ethionamide was 37% whereas linezolid resistance was not detected. Statistically significant correlation was detected between resistance rates of these antibiotic pairs; levofloxacin-ofloxacin (p< 0.01), amikacin-kanamycin (p= 0.01) and streptomycin-ethionamide (p= 0.04). In our study, extensive drug resistance was not encountered in any MDR-TB isolates while high resistance rates was observed against ethionamide and capreomycin. It can be concluded that parenteral aminoglycosides amikasin and kanamycin, fluoroquinolones and linezolid seemed to be reliable anti-TB agents in MDR-TB treatment, however, further larger scale studies are needed.

Türkiyenin Doğusunda Çeşitli Klinik Örneklerden İzole Edilen Mycobacterium tuberculosis Suşlarinin Major Anti-Tüberküloz İlaçlara Duyarlılıklarının Araştırılması

“…[7,8] MDR-TB is defined as TB resistant to caused by M. tuberculosis complex isolates resistant to INH and RIF which are among the primary (first-line) anti-TB drugs. [9,10] In our country, the number of MDR-TB in 2017 patients was 191. In 2015, the treatment success for MDR-TB patients at the 24 th month 2015 was 67.8%.…”

The evaluation of second line drug susceptibilities and molecular epidemiological profiles of multidrug resistance Mycobacterium tuberculosis isolates isoleted from different region of Turkey

“…Bektöre et al (30) investigated the susceptibility status of 81 MDR-TB isolates isolated from MDR-TB patients living in Istanbul, Izmir and Manisa to first-and secondline anti-TB drugs with the fully automated BACTEC MGIT960 system; determined the rates of resistance to second-line anti-TB drugs as 1.2% for Amikacin (AMK) and CAN, 2.5% for OFL and levofloxacin (LVX), 14.8% for CPM, 37% for ETN, and did not detect resistance to LIN. ETN resistance rate in our study was found to be similar to this study.…”

Characterization of resistance mutations against first and second line antituberculosis drugs of multi-drug resistant Mycobacterium tuberculosis strains isolated from clinical samples by In house PCR method and comparison of resistance profiles

“…In patients with MDR-TB, the addition of second-line drugs in addition to first-generation drugs leads to prolongation of treatment 6 . The fact that the second line anti-tuberculosis drugs added to the treatment have more toxic effects and are less effective cause many side effects in patients, but also negatively affect patient compliance 7 .In addition, the cost of second-line drugs is another reason for patients to be negatively affected 8 . Drug resistance in Mycobacterıum tuberculosis (MTB)develops with many mechanisms, althoughit has a different frequency for each antibiotic.These mechanisms can be listed as enzyme inactivation, decrease in permeability, change in antibiotic target, increased efflux mechanisms, and decrease in the activity of enzymes that activate prodrugs 9,10 .Determining resistance quickly and accurately is extremely important in preventing antituberculosis drug resistance 11 .…”