Boyles Tom H, Nduna Matilda, Pitsi Thalitha, Scott Lesley, Fox Matthew P, Maartens Gary
Department of Medicine, University of Cape Town, Cape Town, South Africa.
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Open Forum Infect Dis. 2020 Jan 6;7(2):ofz543. doi: 10.1093/ofid/ofz543. eCollection 2020 Feb.
The use of a "trial of antibiotics" as empiric therapy for bacterial pneumonia as a diagnostic tool for tuberculosis in people with HIV (PWH) was removed from World Health Organization (WHO) recommendations in 2007, based on expert opinion. Current guidelines recommend antibiotics only after 2 Xpert MTB/RIF tests (if available), chest x-ray, and clinical assessment have suggested that tuberculosis is unlikely. Despite this, a "trial of antibiotics" remains common in algorithms in low-resource settings, but its value is uncertain. C-reactive protein (CRP), which has been proposed as a "rule-out" test for tuberculosis, may be an objective marker of response to antibiotics.
We performed a passive case-finding cohort study of adult PWH with a positive WHO symptom screen. All participants received antibiotics at first visit according to the local protocol and were reviewed to ascertain clinical response. Point-of-care CRP was measured at both visits. All patients had sputum tested with Xpert MTB/RIF Ultra (Ultra), and the reference standard was based on 2 sputum mycobacterial cultures. We explored multivariable prediction models (MPM) for tuberculosis based on 1 or 2 visits.
Seventy-five of 207 patients (36%) had confirmed tuberculosis. Clinical response to antibiotics after 2 days was a good predictor of disease. An MPM based on 2 visits, without CRP, had acceptable discrimination (c-statistic, 0.75) and calibration (goodness-of-fit = .07). Addition of CRP after antibiotics improved the model moderately (c-statistic, 0.78). CRP at first visit was not an independent predictor of tuberculosis.
In adult PWH seeking care for symptoms suggestive of tuberculosis, lack of response to antibiotics is a strong predictor of disease and is likely to be useful, particularly when access to Ultra is limited. CRP adds value when measured after antibiotics but is of limited value at first visit.
基于专家意见，2007年世界卫生组织（WHO）的建议不再将使用“抗生素试验”作为对感染艾滋病毒者（PWH）细菌性肺炎的经验性治疗手段及结核病的诊断工具。当前指南建议仅在2次Xpert MTB/RIF检测（若可获得）、胸部X光检查及临床评估均提示不太可能为结核病后才使用抗生素。尽管如此，在资源匮乏地区的诊疗流程中，“抗生素试验”仍然常见，但其价值尚不确定。C反应蛋白（CRP）已被提议作为结核病的“排除”检测指标，可能是对抗生素反应的客观标志物。
我们对世卫组织症状筛查呈阳性的成年PWH进行了一项被动病例发现队列研究。所有参与者在首次就诊时根据当地方案接受抗生素治疗，并接受复查以确定临床反应。两次就诊时均检测即时CRP。所有患者的痰液均采用Xpert MTB/RIF Ultra（Ultra）检测，参考标准基于2次痰液分枝杆菌培养。我们探索了基于1次或2次就诊的结核病多变量预测模型（MPM）。
207例患者中有75例（36%）确诊为结核病。2天后对抗生素的临床反应是疾病的良好预测指标。基于2次就诊且不包括CRP的MPM具有可接受的区分度（c统计量为0.75）和校准度（拟合优度 = 0.07）。抗生素治疗后加入CRP可适度改善模型（c统计量为0.78）。首次就诊时的CRP不是结核病的独立预测指标。
在因疑似结核病症状就诊的成年PWH中，对抗生素无反应是疾病的有力预测指标，可能会很有用，尤其是在获得Ultra检测的机会有限时。抗生素治疗后检测CRP有价值，但首次就诊时价值有限。
