Jacobson Karen R, Barnard Marinus, Kleinman Mary B, Streicher Elizabeth M, Ragan Elizabeth J, White Laura F, Shapira Ofer, Dolby Tania, Simpson John, Scott Lesley, Stevens Wendy, van Helden Paul D, Van Rie Annelies, Warren Robin M
Section of Infectious Diseases, Boston University School of Medicine, Massachusetts.
National Health Laboratory Service, Cape Town, South Africa.
Clin Infect Dis. 2017 Jun 1;64(11):1502-1508. doi: 10.1093/cid/cix128.
BACKGROUND.: Xpert MTB/RIF (Xpert) detects rifampicin-resistant tuberculosis (RR-tuberculosis), enabling physicians to rapidly initiate a World Health Organization-recommended 5-drug regimen while awaiting second-line drug-susceptibility test (DST) results. We quantified the second-line DST results time and proportion of patients potentially placed on suboptimal therapy.
METHODS.: We included RR-tuberculosis patients detected using Xpert at the South African National Health Laboratory Services (NHLS) of the Western Cape between November 2011 and June 2013 and at Eastern Cape, Free State, and Gauteng NHLS between November 2012 and December 2013. We calculated time from specimen collection to phenotypic second-line DST results. We identified isoniazid and ethionamide resistance mutations on line probe assay and performed pyrazinamide sequencing.
RESULTS.: Among 1332 RR-tuberculosis patients, only 44.7% (596) had second-line DST for both fluoroquinolones and second-line injectable: 55.8% (466 of 835) in the Western Cape and 26.2% (130 of 497) in the other provinces. Patients with smear negative disease and age ≤10 years were less likely to have a result (risk ratio [RR] = 0.72; 95% CI, 0.64-0.81 and RR = 0.49; 95% CI, 0.26-0.79). Median time to second-line DST was 53 days (range, 8-259). Of the 252 patients with complete second-line DST, 101 (40.1%) potentially initiated a suboptimal regimen: 46.8% in the Western Cape and 25.3% in the other provinces.
CONCLUSIONS.: Many South Africans diagnosed with RR-tuberculosis by Xpert initiate a suboptimal regimen, with information to adjust therapy available in half of all patients after a median 7 weeks. Algorithm completion and time delays remain challenging.
Xpert MTB/RIF（Xpert）检测利福平耐药结核病（RR结核病），使医生能够在等待二线药敏试验（DST）结果时迅速启动世界卫生组织推荐的五药方案。我们对二线DST结果时间以及可能接受次优治疗的患者比例进行了量化。
我们纳入了2011年11月至2013年6月在西开普省南非国家卫生实验室服务中心（NHLS）以及2012年11月至2013年12月在东开普省、自由邦省和豪登省NHLS使用Xpert检测出的RR结核病患者。我们计算了从标本采集到二线表型DST结果的时间。我们在线探针分析中鉴定异烟肼和乙硫异烟胺耐药突变，并进行吡嗪酰胺测序。
在1332例RR结核病患者中，仅44.7%（596例）接受了氟喹诺酮类药物和二线注射剂的二线DST检测：西开普省为55.8%（835例中的466例），其他省份为26.2%（497例中的130例）。涂片阴性疾病患者和年龄≤10岁的患者获得结果的可能性较小（风险比[RR]=0.72；95%可信区间，0.64 - 0.81；RR = 0.49；95%可信区间，0.26 - 0.79）。二线DST的中位时间为53天（范围，8 - 259天）。在252例完成二线DST检测的患者中，101例（40.1%）可能启动了次优方案：西开普省为46.8%，其他省份为25.3%。
许多通过Xpert诊断为RR结核病的南非人启动了次优方案，在中位7周后，半数患者可获得调整治疗的信息。算法完善和时间延迟仍然具有挑战性。
