Walsh T J, Garrett K, Feurerstein E, Girton M, Allende M, Bacher J, Francesconi A, Schaufele R, Pizzo P A
Infectious Diseases Section, National Cancer Institute, Bethesda, Maryland 20892, USA.
Antimicrob Agents Chemother. 1995 May;39(5):1065-9. doi: 10.1128/AAC.39.5.1065.
Pulmonary infiltrates in neutropenic hosts with invasive aspergillosis are due to vascular invasion and hemorrhagic infarction. In order to measure the effect of antifungal compounds on this organism-mediated tissue injury, we monitored the course of pulmonary infiltrates by serial ultrafast computerized tomography (UFCT) in persistently granulocytopenic rabbits with experimental invasive pulmonary aspergillosis. The course of pulmonary lesions measured by serial UFCT scans was compared with those measured by conventional chest radiography, histopathological resolution of lesions, and microbiological clearance of Aspergillus fumigatus. Treatment groups included either amphotericin B colloidal dispersion in dosages of 1, 5, and 10 mg/kg of body weight per day intravenously or conventional desoxycholate amphotericin B at 1 mg/kg/day intravenously. Therapeutic monitoring of pulmonary lesions by UFCT demonstrated a significant dose-response relationship. Lesions continued to progress in untreated controls, whereas lesions in treated rabbits initially increased and then decreased in response to antifungal therapy in a dosage-dependent manner (P < or = 0.05 to P < or = 0.005, depending upon the groups compared). This same trend of resolution of lesions in response to antifungal therapy was also demonstrated by postmortem examination and by microbiological clearance of the organism. These data indicated that amphotericin B colloidal dispersion at 5 and 10 mg/kg/day exerted a more rapid rate of clearance of lesions than conventional amphotericin B. UFCT was more sensitive than conventional chest radiography in detecting lesions due to invasive pulmonary aspergillosis (P < 0.05 to P < 0.005, depending upon the groups compared). These findings establish a correlation among UFCT-defined lesions, microbiological response, and resolution of pathologically defined lesions in experimental invasive pulmonary aspergillosis. Serial monitoring of UFCT-defined lesions of aspergillosis provides a novel system for determining the antifungal response of organism-mediated tissue injury.
中性粒细胞减少宿主发生侵袭性曲霉病时出现的肺部浸润是由血管侵袭和出血性梗死所致。为了测定抗真菌化合物对这种由病原体介导的组织损伤的作用，我们通过连续超速计算机断层扫描（UFCT）监测了持续性粒细胞减少的实验性侵袭性肺曲霉病兔的肺部浸润过程。将通过连续UFCT扫描测得的肺部病变过程与通过传统胸部X线摄影测得的过程、病变的组织病理学转归以及烟曲霉的微生物学清除情况进行了比较。治疗组包括每天静脉注射剂量为1、5和10mg/kg体重的两性霉素B胶体分散液，或每天静脉注射1mg/kg的传统脱氧胆酸盐两性霉素B。通过UFCT对肺部病变进行治疗监测显示出显著的剂量反应关系。未治疗的对照组病变持续进展，而治疗组兔的病变最初增加，随后随着抗真菌治疗呈剂量依赖性下降（P≤0.05至P≤0.005，取决于所比较的组）。尸检和病原体的微生物学清除也显示出抗真菌治疗后病变消退的相同趋势。这些数据表明，每天5和10mg/kg的两性霉素B胶体分散液比传统两性霉素B能更快速地清除病变。在检测侵袭性肺曲霉病所致病变方面，UFCT比传统胸部X线摄影更敏感（P<0.05至P<0.005，取决于所比较的组）。这些发现确立了在实验性侵袭性肺曲霉病中UFCT界定的病变、微生物学反应和病理学界定病变的消退之间的相关性。对UFCT界定的曲霉病病变进行连续监测为确定病原体介导的组织损伤的抗真菌反应提供了一种新系统。
