Bektöre Bayhan, Haznedaroğlu Tunçer, Baylan Orhan, Ozyurt Mustafa, Ozkütük Nuri, Satana Dilek, Cavuşoğlu Cengiz, Seber Engin
GATA Haydarpasa Training Hospital, Department of Medical Microbiology, Istanbul, Turkey.
Mikrobiyol Bul. 2013 Jan;47(1):59-70. doi: 10.5578/mb.4229.
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.
近年来耐药结核病（TB）病例数量不断增加，这是一个重要的公共卫生问题。广泛耐药结核病（XDR-TB）是指除了对一线抗结核药物异烟肼和利福平耐药外，还对任何氟喹诺酮类药物以及至少一种注射用二线抗结核药物产生耐药（多重耐药结核病（MDR-TB）的定义）。由于MDR-TB病例导致一线抗结核药物治疗失败，如果有二线抗结核药物药敏试验结果，则根据该结果制定治疗方案，若没有，则使用标准治疗方案。尽管建议应根据分离株的药敏试验结果设计个体化抗结核治疗方案，但由于在土耳其等发展中国家通常无法进行二线抗结核药物药敏试验，因此始终需要标准治疗方案。因此，始终需要进行全国性和区域性监测研究以确定耐药模式，以便就标准治疗算法做出决策。在本研究中，旨在调查从伊斯坦布尔、伊兹密尔和马尼萨的各种医疗机构获得的81株MDR-TB分离株中广泛耐药的情况，并确定马尔马拉和爱琴海地区的XDR-TB发病率。此外，我们旨在为临床医生提供流行病学数据，以支持他们为MDR-TB感染选择二线抗结核药物。使用荧光BACTEC MGIT 960系统（美国BD公司）中的改良Middlebrook 7H9肉汤对分离株进行一线和二线抗结核药物的药敏试验。本研究纳入的81株MDR-TB分离株分别来自伊斯坦布尔的43例（53.1%）患者、伊兹密尔的26例（32.1%）患者和马尼萨省的12例（14.8%）患者。在本研究中，未发现任何符合XDR-TB定义的分离株。MDR-TB分离株对阿米卡星和卡那霉素的二线耐药率为1.2%，对氧氟沙星和左氧氟沙星为2.5%，对卷曲霉素为14.8%，对乙硫异烟胺为37%，而未检测到利奈唑胺耐药。这些抗生素对的耐药率之间存在统计学显著相关性；左氧氟沙星-氧氟沙星（p<0.01）、阿米卡星-卡那霉素（p=0.01）和链霉素-乙硫异烟胺（p=0.04）。在我们的研究中，任何MDR-TB分离株均未出现广泛耐药，但对乙硫异烟胺和卷曲霉素观察到高耐药率。可以得出结论，胃肠外氨基糖苷类药物阿米卡星和卡那霉素、氟喹诺酮类药物和利奈唑胺在MDR-TB治疗中似乎是可靠的抗结核药物，然而，还需要进一步的大规模研究。
