Pasipanodya Jotam G, Ogbonna Deborah, Deshpande Devyani, Srivastava Shashikant, Gumbo Tawanda
Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA.
J Antimicrob Chemother. 2017 Sep 1;72(suppl_2):i3-i19. doi: 10.1093/jac/dkx311.
To perform a systematic review and meta-analysis of the level of funding support and the sputum culture conversion rates in pulmonary Mycobacterium avium-intracellulare complex (P-MAC) disease in adult patients without cystic fibrosis or HIV infection, treated with recommended antibiotic regimens.
We performed a literature search to identify clinical trials, prospective studies and registries that reported outcomes in P-MAC patients. Studies that reported P-MAC diagnosis and treatments based on established guidelines met the inclusion criteria and were examined for bias and quality. We modified existing quality scales and came up with a 10 star quality score. Outcomes meta-analysed were sputum conversion incidence ratios (IR) and their 95% CI, weighted for study quality.
Twenty-one studies that examined 28 regimens, including 2534 patients in intent-to-treat analyses and 1968 in per-protocol analyses, were identified. The study quality mean ± SD scores were 5.4 ± 2.2 out of 10 stars. Only two (9.5%) studies received public funding. There was significant heterogeneity of microbial effect among treatment regimens (I2 > 40%; P > 0.001). The pooled IR for sustained sputum conversion was 0.54 (95% CI 0.45-0.63) for macrolide-containing regimens versus 0.38 (0.25-0.52) with macrolide-free regimens. Prolonging therapy duration beyond 12 months was associated with an average decline in sputum conversion to 22% (95% CI 1%-44%).
Researchers working on P-MAC therapy have received very little public funding support. As a result, the evidence base for treatment guidelines is based on studies of relatively small numbers of patients in low-quality studies. Nevertheless, these studies showed poor sputum conversion rates in patients receiving recommended treatment regimens.
对在无囊性纤维化或HIV感染的成年患者中,采用推荐抗生素方案治疗的肺部鸟分枝杆菌复合群(P-MAC)疾病的资金支持水平和痰培养转化率进行系统评价和荟萃分析。
我们进行了文献检索,以确定报告P-MAC患者结局的临床试验、前瞻性研究和登记处。根据既定指南报告P-MAC诊断和治疗的研究符合纳入标准,并对其偏倚和质量进行检查。我们修改了现有的质量量表,并得出了一个10星质量评分。荟萃分析的结局指标是痰转化发病率比(IR)及其95%置信区间,并根据研究质量进行加权。
共纳入21项研究,这些研究检验了28种治疗方案,意向性分析中有2534例患者,符合方案分析中有1968例患者。研究质量的平均±标准差评分为5.4±2.2(满分10星)。只有两项(9.5%)研究获得了公共资金。治疗方案之间的微生物效应存在显著异质性(I2>40%;P>0.001)。含大环内酯类方案的持续痰转化合并IR为0.54(95%CI 0.45-0.63),而不含大环内酯类方案为0.38(0.25-0.52)。将治疗时间延长至12个月以上与痰转化率平均下降至22%(95%CI 1%-44%)相关。
从事P-MAC治疗研究的人员获得的公共资金支持非常少。因此,治疗指南的证据基础是基于低质量研究中相对少量患者的研究。尽管如此,这些研究显示接受推荐治疗方案的患者痰转化率较低。