曲霉菌耐药性正快速增强

潮水

Clin Infect Dis. (2011) 52 (9): 1123-1129.
High-frequency Triazole Resistance Found In Nonculturable Aspergillus fumigatus from Lungs of Patients with Chronic Fungal Disease

Abstract

Background. Oral triazole therapy is well established for the treatment of invasive (IPA), allergic (ABPA), and chronic pulmonary (CPA) aspergillosis, and is often long-term. Triazole resistance rates are rising internationally. Microbiological diagnosis of aspergillosis is limited by poor culture yield, leading to uncertainty about the frequency of triazole resistance.

Methods.Using an ultrasensitive real-time polymerase chain reaction (PCR) assay for Aspergillus spp., we assessed respiratory fungal load in bronchoalveolar lavage (BAL) and sputum specimens. In a subset of PCR-positive, culture negative samples, we further amplified the CYP51A gene to detect key single-nucleotide polymorphisms (SNPs) associated with triazole resistance.

Results.Aspergillus DNA was detected in BAL from normal volunteers (4/11, 36.4%) and patients with culture or microscopy confirmed IPA (21/22, 95%). Aspergillus DNA was detected in sputum in 15 of 19 (78.9%) and 30 of 42 (71.4%) patients with ABPA and CPA, compared with 0% and 16.7% by culture, respectively. In culture-negative, PCR-positive samples, we detected triazole-resistance mutations (L98H with tandem repeat [TR] and M220) within the drug target CYP51A in 55.1% of samples. Six of 8 (75%) of those with ABPA and 12 of 24 (50%) with CPA had resistance markers present, some without prior triazole treatment, and in most despite adequate plasma drug concentrations around the time of sampling.

Conclusions.The very low organism burdens of fungi causing infection have previously prevented direct culture and detection of antifungal resistance in clinical samples. These findings have major implications for the sustainability of triazoles for human antifungal therapy.

英国研究人员日前报告说，最近对一些曲霉菌感染者的化验显示，这种细菌对现在常用的三唑类抗菌药的耐药性正在快速增强，具有这种耐药性的曲霉菌在逐渐传播，这种趋势值得医学界警惕。

英国曼彻斯特大学研究人员在新一期美国《临床传染病》杂志上报告说，他们最近对一批感染曲霉菌的患者进行了化验，结果发现55%的被检测者体内的曲霉菌都具有一些耐药性特征，对常用于抗菌的三唑类药物表现出耐药性。而就在两年前的一次检查中，这一比例还只是28%％。

此外，还有迹象显示具有耐药性的曲霉菌正在广泛传播。研究人员检查了8名从未使用过三唑类药物的病人，结果发现其中6人体内的曲霉菌也都有耐药性。

研究人员戴维·丹宁说，本次研究发现的曲霉菌耐药性比例非常高，数据显示这种细菌的耐药性正在快速增强，这值得医疗界警惕。

他认为，造成曲霉菌耐药性增强的原因可能有两个方面，一是现在农业上使用的许多杀虫剂都含有三唑类药物成分；一是在临床治疗中长期使用三唑类药物。这两方面都可能使细菌在不致命剂量药物的“锻炼”下发展出耐药性。

对人类而言，曲霉菌常会导致肺部疾病，会加重哮喘患者的症状，此外对那些有其他肺部感染或免疫系统受损的患者来说，也可能会使病情加重。

星火

近期遇到一例曲霉菌硬膜外感染灶，困惑耐药性，不知道如何控制。

5ej

感谢楼主，学习了！