Pham Ngoc Thach Hospital, 120 Hung Vuong, District 5, Ho Chi Minh City, Viet Nam.
BMC Infect Dis. 2012 Mar 1;12:49. doi: 10.1186/1471-2334-12-49.
Early diagnosis of tuberculosis (TB) and multidrug resistant tuberculosis (MDR TB) is important for the elimination of TB. We evaluated the microscopic observation drug susceptibility (MODS) assay as a direct rapid drug susceptibility testing (DST) method for MDR-TB screening in sputum samples
All adult TB suspects, who were newly presenting to Pham Ngoc Thach Hospital from August to November 2008 were enrolled into the study. Processed sputum samples were used for DST by MODS (DST-MODS) (Rifampicin (RIF) 1 μg/ml and Isoniazid (INH) 0.4 μg/ml), MGIT culture (Mycobacterial Growth Indicator Tube) and Lowenstein Jensen (LJ) culture. Cultures positive by either MGIT or LJ were used for proportional DST (DST-LJ) (RIF 40 μg/ml and INH 0.2 μg/ml). DST profiles on MODS and LJ were compared. Discrepant results were resolved by multiplex allele specific PCR (MAS-PCR).
Seven hundred and nine TB suspects/samples were enrolled into the study, of which 300 samples with DST profiles available from both MODS and DST-LJ were analyzed. Cording in MODS was unable to correctly identify 3 Mycobacteria Other Than Tuberculosis (MOTT) isolates, resulting in 3 false positive TB diagnoses. None of these isolates were identified as MDR-TB by MODS. The sensitivity and specificity of MODS were 72.6% (95%CI: 59.8, 83.1) and 97.9% (95%CI: 95.2, 99.3), respectively for detection of INH resistant isolates, 72.7% (95%CI: 30.9, 93.7) and 99.7% (95%CI: 98.1, 99.9), respectively for detecting RIF resistant isolates and 77.8% (95%CI: 39.9, 97.1) and 99.7% (95%CI: 98.1, 99.9), respectively for detecting MDR isolates. The positive and negative predictive values (PPV and NPV) of DST-MODS were 87.5% (95%CI: 47.3, 99.6) and 99.3% (95%CI: 97.5, 99.9) for detection of MDR isolates; and the agreement between MODS and DST-LJ was 99.0% (kappa: 0.8, P < 0.001) for MDR diagnosis. The low sensitivity of MODS for drug resistance detection was probably due to low bacterial load samples and the high INH concentration (0.4 μg/ml). The low PPV of DST-MODS may be due to the low MDR-TB rate in the study population (3.8%). The turnaround time of DST-MODS was 9 days and 53 days for DST-LJ.
The DST-MODS technique is rapid with low contamination rates. However, the sensitivity of DST-MODS for detection of INH and RIF resistance in this study was lower than reported from other settings.
早期诊断结核病（TB）和耐多药结核病（MDR-TB）对于消除结核病至关重要。我们评估了显微镜观察药物敏感性（MODS）检测作为 MDR-TB 筛查的直接快速药物敏感性检测（DST）方法，该方法用于痰液样本。
2008 年 8 月至 11 月期间，新向 Pham Ngoc Thach 医院就诊的所有成年 TB 疑似患者均纳入本研究。用 MODS（DST-MODS）（利福平（RIF）1μg/ml 和异烟肼（INH）0.4μg/ml）、MGIT 培养（分枝杆菌生长指示管）和 Lowenstein Jensen（LJ）培养对处理过的痰液样本进行 DST。MGIT 或 LJ 培养阳性的样本用于比例 DST（DST-LJ）（RIF 40μg/ml 和 INH 0.2μg/ml）。比较 MODS 和 LJ 上的 DST 谱。通过多重等位基因特异性 PCR（MAS-PCR）解决不一致的结果。
共纳入 709 例 TB 疑似患者/样本，其中 300 例样本可从 MODS 和 DST-LJ 获得 DST 谱进行分析。MODS 中的分枝杆菌属鉴定不能正确识别 3 株非结核分枝杆菌（MOTT）分离株，导致 3 例 TB 假阳性诊断。这些分离株均未被 MODS 鉴定为 MDR-TB。MODS 检测 INH 耐药株的敏感性和特异性分别为 72.6%（95%CI：59.8，83.1）和 97.9%（95%CI：95.2，99.3），检测 RIF 耐药株的敏感性和特异性分别为 72.7%（95%CI：30.9，93.7）和 99.7%（95%CI：98.1，99.9），检测 MDR 株的敏感性和特异性分别为 77.8%（95%CI：39.9，97.1）和 99.7%（95%CI：98.1，99.9）。DST-MODS 的阳性和阴性预测值（PPV 和 NPV）分别为 87.5%（95%CI：47.3，99.6）和 99.3%（95%CI：97.5，99.9），用于检测 MDR 株；MODS 和 DST-LJ 之间的一致性为 99.0%（kappa：0.8，P <0.001），用于 MDR 诊断。MODS 对耐药性检测的敏感性较低可能是由于样本细菌载量低和 INH 浓度高（0.4μg/ml）所致。DST-MODS 的低 PPV 可能是由于研究人群中 MDR-TB 率较低（3.8%）所致。DST-MODS 的周转时间为 9 天，DST-LJ 的周转时间为 53 天。
DST-MODS 技术快速，污染率低。然而，在本研究中，DST-MODS 检测 INH 和 RIF 耐药性的敏感性低于其他环境的报道。
