Department of Obstetrics and Gynecology, Maine Medical Center, Portland, Maine, USA.
Antimicrob Agents Chemother. 2012 Mar;56(3):1403-6. doi: 10.1128/AAC.05025-11. Epub 2012 Jan 9.
The treatment of vulvovaginal candidiasis (VVC) due to Candida glabrata is challenging, with limited therapeutic options. Unexplained disappointing clinical efficacy has been reported with systemic and topical azole antifungal agents in spite of in vitro susceptibility. Given that the vaginal pH of patients with VVC is unchanged at 4 to 4.5, we studied the effect of pH on the in vitro activity of 11 antifungal agents against 40 C. glabrata isolates and compared activity against 15 fluconazole-sensitive and 10 reduced-fluconazole-susceptibility C. albicans strains. In vitro susceptibility to flucytosine, fluconazole, voriconazole, posaconazole, itraconazole, ketoconazole, clotrimazole, miconazole, ciclopirox olamine, amphotericin B, and caspofungin was determined using the CLSI method for yeast susceptibility testing. Test media were buffered to pHs of 7, 6, 5, and 4. Under conditions of reduced pH, C. glabrata isolates remained susceptible to caspofungin and flucytosine; however, there was a dramatic increase in the MIC(90) for amphotericin B and every azole drug tested. Although susceptible to other azole drugs tested at pH 7, C. albicans strains with reduced fluconazole susceptibility also demonstrated reduced susceptibility to amphotericin B and all azoles at pH 4. In contrast, fluconazole-sensitive C. albicans isolates remained susceptible at low pH to azoles, in keeping with clinical observations. In selecting agents for treatment of recurrent C. glabrata vaginitis, clinicians should recognize the limitations of in vitro susceptibility testing utilizing pH 7.0.
外阴阴道假丝酵母菌病（VVC）的治疗具有挑战性，因为针对光滑假丝酵母菌（Candida glabrata）的治疗选择有限。尽管体外药敏试验显示对唑类抗真菌药物敏感，但全身和局部应用唑类抗真菌药物的临床疗效却令人失望，原因不明。鉴于 VVC 患者的阴道 pH 值在 4 到 4.5 之间保持不变，我们研究了 pH 值对 11 种抗真菌药物对 40 株光滑假丝酵母菌的体外活性的影响，并比较了这些药物对 15 株氟康唑敏感和 10 株氟康唑敏感性降低的白假丝酵母菌菌株的活性。使用 CLSI 酵母药敏试验方法测定氟胞嘧啶、氟康唑、伏立康唑、泊沙康唑、伊曲康唑、酮康唑、克霉唑、咪康唑、环吡酮胺、两性霉素 B 和卡泊芬净的体外药敏性。测试培养基的 pH 值分别缓冲至 7、6、5 和 4。在 pH 值降低的条件下，光滑假丝酵母菌分离株对卡泊芬净和氟胞嘧啶仍保持敏感；然而，两性霉素 B 和所测试的每种唑类药物的 MIC90 值显著增加。尽管在 pH 7 时对其他唑类药物敏感，但氟康唑敏感性降低的白假丝酵母菌菌株在 pH 4 时对两性霉素 B 和所有唑类药物的敏感性也降低。相比之下，氟康唑敏感的白假丝酵母菌分离株在低 pH 值时仍对唑类药物保持敏感性，这与临床观察一致。在选择治疗复发性光滑假丝酵母菌阴道炎的药物时，临床医生应认识到利用 pH 7.0 进行体外药敏试验的局限性。
