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首页> 外文期刊>Journal of Clinical Microbiology >Emergence of Resistance of Candida albicans to Clotrimazole in Human Immunodeficiency Virus-Infected Children: In Vitro and Clinical Correlations
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Emergence of Resistance of Candida albicans to Clotrimazole in Human Immunodeficiency Virus-Infected Children: In Vitro and Clinical Correlations

机译：在人类免疫缺陷病毒感染儿童中白色念珠菌对克霉唑的抗药性的出现：体外和临床相关性。

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Oropharyngeal candidiasis (OPC) is a common opportunistic infection in human immunodeficiency virus (HIV)-infected patients and other immunocompromised hosts. Clotrimazole troches are widely used in the treatment of mucosal candidiasis. However, little is known about the potential contribution of clotrimazole resistance to the development of refractory mucosal candidiasis. We therefore investigated the potential emergence of resistance to clotrimazole in a prospectively monitored HIV-infected pediatric population receiving this azole. Adapting the National Committee for Clinical Laboratory Standards M27-A reference method for broth antifungal susceptibility testing of yeasts to clotrimazole, we compared MICs in macrodilution and microdilution assays. We further analyzed the correlation between these in vitro findings and the clinical response to antifungal therapy. One isolate from each of 87 HIV-infected children was studied by the macrodilution and microdilution methods. Two inoculum sizes were tested by the macrodilution method (103 and 104 CFU/ml) in order to assess the effect of inoculum size on clotrimazole MICs. The same isolates also were tested using a noncolorimetric microdilution method. Clotrimazole concentrations ranged from 0.03 to 16 μg/ml. Readings were performed after incubation for 24 and 48 h at 35°C. For 62 (71.2%) of 87 clinical isolates, the MICs were low (≤0.06 μg/ml). The MIC for 90% of the strains tested was 0.5 μg/ml, and the highest MIC was 8 μg/ml. There was no significant difference between MICs at the two inoculum sizes. There was 89% agreement (±1 tube) between the microdilution method at 24 h and the macrodilution method at 48 h. If the MIC of clotrimazole for an isolate of C. albicans was ≥0.5 μg/ml, there was a significant risk (P < 0.001) of cross-resistance to other azoles: fluconazole, ≥64 μg/ml (relative risk [RR] = 8.9); itraconazole, ≥1 μg/ml (RR = 10). Resistance to clotrimazole was highly associated with clinically overt failure of antifungal azole therapy. Six (40%) of 15 patients for whom the clotrimazole MIC was ≥0.5 μg/ml required amphotericin B for refractory mucosal candidiasis versus 4 (5.5%) of 72 for whom the MIC was <0.5 μg/ml (P = 0.001; 95% confidence interval = 2.3 to 22; RR = 7.2). These findings suggest that an interpretive breakpoint of 0.5 μg/ml may be useful in defining clotrimazole resistance in C. albicans. The clinical laboratory's ability to determine MICs of clotrimazole may help to distinguish microbiologic resistance from the other causes of refractory OPC, possibly reducing the usage of systemic antifungal agents. We conclude that resistance to clotrimazole develops in isolates of C. albicans from HIV-infected children, that cross-resistance to other azoles may develop concomitantly, and that this resistance correlates with refractory mucosal candidiasis.
机译：口咽念珠菌病（OPC）是感染人类免疫缺陷病毒（HIV）的患者和其他免疫功能低下宿主的常见机会性感染。克霉唑锭剂被广泛用于粘膜念珠菌病的治疗。然而，关于克霉唑抗药性对难治性粘膜念珠菌病发展的潜在贡献知之甚少。因此，我们在接受该唑的前瞻性监测HIV感染儿科患者中调查了对克霉唑耐药的潜在出现。我们采用了美国国家临床实验室标准委员会M27-A对酵母对克霉唑的肉汤抗真菌药敏性测试的参考方法，我们比较了大稀释和微量稀释测定中的MIC。我们进一步分析了这些体外发现与抗真菌治疗的临床反应之间的相关性。通过宏观稀释和微量稀释方法研究了87名HIV感染儿童的每一个分离株。通过大稀释法测试了两种接种量（10 3 和10 4 CFU / ml），以评估接种量对克霉唑MIC的影响。还使用非比色微量稀释法测试了相同的分离物。克霉唑的浓度范围为0.03至16μg/ ml。在35°C孵育24和48小时后进行读数。对于87个临床分离株中的62个（71.2％），MIC较低（≤0.06μg/ ml）。 90％的菌株的MIC为0.5μg/ ml，最高MIC为8μg/ ml。两种接种物大小的MIC之间没有显着差异。 24小时的微稀释方法与48小时的大稀释方法之间有89％的一致性（±1管）。如果克霉唑的MIC为 C的分离株。白色念珠菌≥0.5μg/ ml，与其他唑类药物氟康唑交叉耐药的显着风险（ P <0.001）（相对风险[RR] = 8.9）;伊曲康唑，≥1μg/ ml（RR = 10）。对克霉唑的耐药性与抗真菌唑治疗的临床明显失败密切相关。克霉唑MIC≥0.5μg/ ml的15名患者中有6名（40％）难治性粘膜念珠菌病需要两性霉素B，而MIC <0.5μg/ ml的72名中有4名（5.5％） / em> = 0.001; 95％置信区间= 2.3至22; RR = 7.2）。这些发现表明，0.5μg/ ml的解释性断点可能对确定C中克霉唑的耐药性有用。白色的。临床实验室确定克霉唑MIC的能力可能有助于将微生物耐药性与难治性OPC的其他原因区分开，可能会减少全身性抗真菌药的使用。我们得出的结论是，对克霉唑的抗性在 C分离株中发展。来自感染HIV的儿童的白色念珠菌，可能与其他唑类产生交叉耐药性，并且这种耐药性与难治性粘膜念珠菌病有关。

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