Wirth Fernanda, de Azevedo Maria Isabel, Pilla Carmen, Aquino Valério Rodrigues, Neto Gustavo Wissmann, Goldani Luciano Zubaran
Universidade Federal do Rio Grande do Sul, Faculdade de Medicina, Ramiro Barcelos, 2400. Porto Alegre, RS, Brazil.
Hospital de Clínicas de Porto Alegre (HCPA), Section of Infectious Diseases. Ramiro Barcelos, 2350. Porto Alegre, RS, Brazil.
Med Mycol. 2018 Apr 1;56(3):257-262. doi: 10.1093/mmy/myx054.
The purpose of this study was to evaluate the influence of intracranial hypertension in the cerebrospinal fluid (CSF) levels of amphotericin B and fluconazole levels of patients with cryptococcal meningitis. CSF samples and intracranial pressure were obtained by means of routine punctures performed at days 1, 7, and 14 of therapy, respectively. Amphotericin B and fluconazole CSF levels were measured by HPLC method as previously described. The minimum inhibitory concentration for amphotericin B, fluconazole, 5΄flucytosine, and voriconazole of each Cryptococcus isolate was performed according to CLSI. The predominant Cryptococcus species found was C. neoformans, and the major underlying condition was AIDS. Only one CSF sample had a detectable level for amphotericin B during the 14 days of therapy. Fluconazole CSF levels progressively increased from day 1 to day 14 of therapy for most cases. Fluconazole levels in the CSF were above the minimum inhibitory concentrations (MICs) for Cryptococcus during the initial 14 days of antifungal therapy. Variations of intracranial pressure did not affect amphotericin B and fluconazole levels in the CSF. The generalized estimating correlation (GEE) and Spearman correlation test (SCT) showed no significant correlation between the amphotericin B or fluconazole concentrations in the CSF and intracranial pressure (P = .953 and P = .093, respectively for GEE test and P = .477 and P = .847, respectively, for SCT). Combination therapy of amphotericin B with fluconazole was effective in 60% of the patients considering CSF cultures were negative in 9 of 15 patients after 14 days of therapy. Further studies are necessary to evaluate the role of intracranial hypertension on the therapeutic efficacy of different antifungal agents in patients with cryptococcal meningitis.
本研究的目的是评估颅内高压对隐球菌性脑膜炎患者脑脊液中两性霉素B水平及氟康唑水平的影响。分别在治疗的第1天、第7天和第14天通过常规穿刺获取脑脊液样本和颅内压。两性霉素B和氟康唑的脑脊液水平采用先前描述的高效液相色谱法进行测定。根据临床和实验室标准协会（CLSI）对每种隐球菌分离株的两性霉素B、氟康唑、5-氟胞嘧啶和伏立康唑的最低抑菌浓度进行测定。发现的主要隐球菌种类为新型隐球菌，主要基础疾病为艾滋病。在治疗的14天内，只有一份脑脊液样本检测到两性霉素B水平。在大多数病例中，氟康唑的脑脊液水平从治疗第1天到第14天逐渐升高。在抗真菌治疗的最初14天内，脑脊液中的氟康唑水平高于隐球菌的最低抑菌浓度（MICs）。颅内压的变化不影响脑脊液中两性霉素B和氟康唑的水平。广义估计相关性（GEE）和Spearman相关性检验（SCT）显示，脑脊液中两性霉素B或氟康唑浓度与颅内压之间无显著相关性（GEE检验分别为P = 0.953和P = 0.093，SCT分别为P = 0.477和P = 0.847）。考虑到15例患者中有9例在治疗14天后脑脊液培养为阴性，两性霉素B与氟康唑联合治疗对60%的患者有效。有必要进一步研究评估颅内高压对隐球菌性脑膜炎患者不同抗真菌药物治疗效果的作用。
