Paterson P J, Seaton S, Prentice H G, Kibbler C C
Departments of Microbiology and Haematology, Royal Free and University College Medical School, Royal Free Campus and Royal Free Hospital, Pond Street, London NW3 2QG, UK.
J Antimicrob Chemother. 2003 Nov;52(5):873-6. doi: 10.1093/jac/dkg434. Epub 2003 Sep 30.
To determine whether treatment failure in invasive aspergillosis (IA) is the result of resistance of Aspergillus spp. isolates to amphotericin B.
Six Aspergillus fumigatus and six Aspergillus flavus isolates cultured from deep tissue biopsies in 11 patients with haematological malignancies during 1991-1998 were tested. A method based on the NCCLS M38-A broth microdilution method, with colorimetric determination of MICs, was used to determine the MICs of amphotericin B and itraconazole.
All A. fumigatus isolates were susceptible to amphotericin B (MIC 0.25-0.5 mg/L), as were three A. flavus isolates (MIC 1 mg/L), but three were less susceptible (MIC 2 mg/L). All isolates were susceptible to itraconazole (MIC 0.125-0.25 mg/L). All patients had been treated with amphotericin B, having received a median of 12 days of treatment when the tissue was obtained.
The difficulty in treating IA may not be because of the susceptibility of the isolates, but because of poor penetration of antifungal agents into infected tissue. Aspergillus spp. invade blood vessels causing thrombosis and tissue infarction, and therefore it may be difficult for antifungal drugs to exceed MICs in infected tissues. This highlights the need for different treatment strategies, such as surgery and the administration of cytokines.
确定侵袭性曲霉病（IA）治疗失败是否是由于曲霉属分离株对两性霉素B耐药所致。
对1991年至1998年间从11例血液系统恶性肿瘤患者的深部组织活检中培养出的6株烟曲霉和6株黄曲霉分离株进行检测。采用基于NCCLS M38 - A肉汤微量稀释法并通过比色法测定最低抑菌浓度（MIC）的方法，来确定两性霉素B和伊曲康唑的MIC。
所有烟曲霉分离株对两性霉素B敏感（MIC为0.25 - 0.5mg/L），3株黄曲霉分离株也敏感（MIC为1mg/L），但有3株敏感性较差（MIC为2mg/L）。所有分离株对伊曲康唑敏感（MIC为0.125 - 0.25mg/L）。所有患者均接受过两性霉素B治疗，获取组织时接受治疗的中位天数为12天。
IA治疗困难可能并非因为分离株的敏感性，而是因为抗真菌药物难以渗透到感染组织中。曲霉属侵入血管导致血栓形成和组织梗死，因此抗真菌药物可能难以在感染组织中超过MIC。这凸显了需要采用不同的治疗策略，如手术和给予细胞因子。
