Cartledge J D, Midgley J, Gazzard B G
Department of HIV/GU Medicine, St Stephen's Centre, Chelsea and Westminster Hospital, London, UK.
AIDS. 1997 Dec;11(15):1839-44. doi: 10.1097/00002030-199715000-00008.
To determine the proportion of fluconazole-resistant Candida albicans isolates that have clinically significant cross-resistance to itraconazole or ketoconazole, that is sufficient to result in failure of these agents at their standard doses (200 and 400 mg daily for 7 days, respectively).
Seven hundred C. albicans isolates from HIV-positive patients with oral candidosis underwent susceptibility testing using a relative growth method, for which cut-off values corresponding to clinical drug failure have been established.
A total of 431 isolates were fully azole-susceptible and three main resistance patterns were detected: isolates resistant to fluconazole alone (n = 100); isolates resistant to fluconazole and ketoconazole but susceptible to itraconazole (n = 94); and isolates resistant to all three drugs (n = 50). No isolates were consistently resistant to ketoconazole without being fluconazole-resistant, and no itraconazole resistance was detected without ketoconazole resistance. Resistance to fluconazole alone was more common in specimens obtained soon after first clinical fluconazole failure, whereas specimens from patients with a longer history of fluconazole-unresponsive candidosis were more likely to be infected with cross-resistant isolates. Median days of prior azole exposure and cumulative fluconazole dose were significantly less for those with isolates resistant to fluconazole alone than for those with ketoconazole cross-resistant isolates, who had received less azole therapy and smaller cumulative fluconazole doses than those with isolates cross-resistant to all three drugs (although not statistically significant). After the diagnosis of fluconazole-unresponsive candidosis, increasing cumulative doses of itraconazole solution were associated with increasing likelihood of cross-resistance.
Clinically significant cross-resistance to other azoles may occur in fluconazole-resistant isolates of C. albicans, although initially most isolates are not cross-resistant and the detection of cross-resistant isolates is associated with a history of greater prior azole exposure. Patients who have been treated for fluconazole-resistant candidosis for longer and with greater cumulative doses of itraconazole solution tend to become infected with increasingly cross-resistant isolates of C. albicans.
确定对氟康唑耐药的白色念珠菌分离株中，对伊曲康唑或酮康唑具有临床显著交叉耐药性的比例，这种交叉耐药性足以导致这些药物在标准剂量（分别为每日200和400毫克，持续7天）下治疗失败。
对700株来自患有口腔念珠菌病的HIV阳性患者的白色念珠菌分离株，采用相对生长法进行药敏试验，已确定了与临床药物治疗失败相对应的临界值。
共有431株分离株对唑类药物完全敏感，检测到三种主要耐药模式：仅对氟康唑耐药的分离株（n = 100）；对氟康唑和酮康唑耐药但对伊曲康唑敏感的分离株（n = 94）；对所有三种药物均耐药的分离株（n = 50）。没有分离株在对氟康唑不耐药的情况下持续对酮康唑耐药，也没有在对酮康唑不耐药的情况下检测到伊曲康唑耐药。仅对氟康唑耐药在首次临床氟康唑治疗失败后不久获得的标本中更为常见，而来自对氟康唑无反应的念珠菌病病史较长的患者的标本更有可能感染交叉耐药分离株。仅对氟康唑耐药的分离株患者的先前唑类药物暴露天数中位数和累积氟康唑剂量，显著低于对酮康唑有交叉耐药性的分离株患者，后者接受的唑类药物治疗和累积氟康唑剂量均低于对所有三种药物均有交叉耐药性的分离株患者（尽管无统计学意义）。在诊断为对氟康唑无反应的念珠菌病后，伊曲康唑溶液累积剂量增加与交叉耐药可能性增加相关。
在对氟康唑耐药的白色念珠菌分离株中可能会出现对其他唑类药物的临床显著交叉耐药性，尽管最初大多数分离株没有交叉耐药性，且交叉耐药分离株的检测与先前更大的唑类药物暴露史相关。接受氟康唑耐药念珠菌病治疗时间更长且伊曲康唑溶液累积剂量更大的患者，往往会感染交叉耐药性越来越高的白色念珠菌分离株。
