Sohnle P G, Hahn B L, Erdmann M D
Division of Infectious Diseases, Medical College of Wisconsin, Milwaukee 53226, USA.
Antimicrob Agents Chemother. 1996 Nov;40(11):2622-5. doi: 10.1128/AAC.40.11.2622.
The treatment of chronic mycoses may expose the infecting organisms to antimicrobial agents for extended periods of time. It is possible that an azole antifungal drug such as fluconazole, with primarily fungistatic activity in standard in vitro susceptibility tests, might be able to damage the fungal cells and reduce their viability over prolonged incubations under nonproliferating conditions. To test this possibility, Candida albicans yeast cells were exposed to various concentrations of fluconazole in RPMI 1640 tissue culture medium for 4 h at 37 degrees C, washed free of the drug, and then incubated at 37 degrees C for a 28-day period; enumeration of the remaining CFU at various times during this period revealed no increased loss of viability for the fluconazole-exposed organisms. However, when fluconazole was added to the organisms maintained in distilled water (with or without pretreatment with the drug), a marked reduction of viability was found. At 14 days of incubation with two strains of C. albicans, negative cultures were found for 7 of 10 and 10 of 11 samples, respectively, containing 1.0 microgram of fluconazole per ml versus 0 of 10 and 1 of 11 control samples (P of < 0.01 and 0.001, respectively). The effect of fluconazole on fungal viability under these conditions became noticeable at approximately 7 days and was greater when the samples were incubated at 37 degrees C rather than 25 degrees C. These findings suggest that fluconazole may have fungicidal effects on fungal cells during prolonged exposures under conditions in which the organisms are prevented from proliferating by lack of nutrients.
慢性真菌病的治疗可能会使感染的生物体长时间接触抗菌药物。在标准体外药敏试验中主要具有抑菌活性的唑类抗真菌药物，如氟康唑，有可能在非增殖条件下长时间孵育后损害真菌细胞并降低其活力。为了验证这种可能性，将白色念珠菌酵母细胞在37℃下于RPMI 1640组织培养基中暴露于不同浓度的氟康唑4小时，洗去药物，然后在37℃下孵育28天；在此期间不同时间对剩余菌落形成单位（CFU）进行计数，结果显示氟康唑处理过的生物体活力丧失并未增加。然而，当将氟康唑添加到保存在蒸馏水中的生物体中（无论是否用该药物预处理）时，发现其活力显著降低。在对两株白色念珠菌进行14天孵育时，每毫升含1.0微克氟康唑的样本中，分别有10个样本中的7个和11个样本中的10个培养结果为阴性，而对照样本中10个样本中的0个和11个样本中的1个培养结果为阴性（P值分别<0.01和0.001）。在这些条件下，氟康唑对真菌活力的影响在大约7天时变得明显，并且当样本在37℃而不是25℃下孵育时影响更大。这些发现表明，在生物体因缺乏营养而无法增殖的条件下长时间暴露时，氟康唑可能对真菌细胞具有杀菌作用。
