背景:在过去的几十年里,与特比萘芬耐药毛癣菌相关的复发性皮肤癣菌病的发病率增加,对皮肤癣菌病的治疗提出了严峻的挑战。治疗失败的独立报告和抗真菌药的最低抑菌浓度(MIC)高,但与MIC和临床结局相关的数据仍然很少.因此,本研究旨在评估全身治疗皮肤癣菌病的结局及其与此类患者分离的病原体MIC的相关性.
方法:对2017年3月至2019年3月587例皮肤癣菌病患者进行回顾性分析。记录了患者的人口统计学和临床细节,以及直接显微镜和真菌培养的结果。通过对rDNA的内部转录间隔区进行测序来鉴定分离物。抗真菌药敏试验按照CLSIM38方案进行。通过DNA测序和ARMS-PCR检测角鲨烯环氧酶(SE)基因的突变。基于培养阳性和规定的全身抗真菌药,患者分为接受特比萘芬全身性治疗的I组培养阳性病例和接受伊曲康唑全身性治疗的II组培养阳性病例,每次共12周。
结果:在本研究中,477(81.39%)为文化阳性;然而,对294名患者(I-157组和II-137组)进行了12周的随访,这些患者被纳入统计分析。两组[I-37/63组(51.4%)和II-14/54组(58.3%)],如果在患病后<6个月内开始治疗,则观察到更好的治愈率。治疗结果显示,如果治疗延长8-12周,伊曲康唑(OddRatio-15.5)或特比萘芬(OddRatio-4.34)的治愈率几率显著提高(p<.001)。在第I组中有41例(治愈18例和未治愈23例)和第II组中有39例(治愈16例和未治愈23例),特比萘芬的MIC较高。来自治愈(I-17/18组;94.4%和II-14/16组;87.5%)和未治愈(I-20/23组;86.9%和II-21/23组;91.3%)的病例在SE基因中具有F397L突变。毛癣菌属患者的治愈率没有显着差异。特比萘芬MIC≥1或<1μg/mL(I组-p=.712和II组-p=.69)。
结论:这项研究表明,延长特比萘芬或伊曲康唑治疗8周以上而不是标准的4周可显著提高治愈率。此外,在抗真菌药物敏感性和临床结局之间未观察到相关性.MIC仍然是定义抗真菌活性和预测抗真菌剂针对特定真菌的效力的主要参数。然而,仅基于真菌菌株的MIC预测治疗成功并不总是可靠的,因为研究表明,体外数据和体内结果之间的相关性较差。为了解决这个问题,需要进一步将抗真菌药敏试验(AFST)数据与临床结局和治疗药物监测相关.它还强调,在疾病<6个月内开始治疗可提高治愈率并减少复发。需要进行广泛的研究以建立更好的皮肤癣菌病治疗方案。
BACKGROUND: Over the past decades, the increasing incidence of recurrent dermatophytosis associated with
terbinafine-resistant Trichophyton has posed a serious challenge in management of dermatophytosis. Independent reports of failure of treatment and high minimum inhibitory concentrations (MIC) of antifungals are available, but data correlating MIC and clinical outcomes is still sparse. Therefore, the present study was conducted to evaluate the outcomes of systemic treatment of dermatophytosis and its correlation with MIC of the etiological agents isolated from such patients.
METHODS: Retrospective analysis of 587 consecutive patients with dermatophytosis was done from March 2017 to March 2019. Demographic and clinical details of the patients were noted, along with the results of direct microscopy and fungal culture. The isolates were identified by sequencing the internal transcribed spacer region of rDNA. Antifungal susceptibility testing was performed following the CLSI M38 protocol. Mutation in the squalene epoxidase (SE) gene was detected by DNA sequencing and ARMS-PCR. Based on the culture-positivity and prescribed systemic antifungal, patients were categorised into Group I culture-positive cases treated with systemic terbinafine and Group II culture-positive cases treated with systemic itraconazole, each for a total period of 12 weeks.
RESULTS: In the present study, 477 (81.39%) were culture-positive; however, 12 weeks follow-up was available for 294 patients (Group I-157 and Group II-137) who were included for statistical analysis. In both groups [Group I-37/63 (51.4%) and Group II-14/54 (58.3%)], a better cure rate was observed if the initiation of therapy was performed within <6 months of illness. Treatment outcome revealed that if therapy was extended for 8-12 weeks, the odds of cure rate are significantly better (p < .001) with either itraconazole (Odd Ratio-15.5) or
terbinafine (Odd Ratio-4.34). Higher MICs for
terbinafine were noted in 41 cases (cured-18 and uncured-23) in Group I and 39 cases (cured-16 and uncured-23) in Group II. From cured (Group I-17/18; 94.4% and Group II-14/16; 87.5%) and uncured (Group I-20/23; 86.9% and Group II-21/23; 91.3%) cases had F397L mutation in the SE gene. No significant difference in cure rate was observed in patients with Trichophyton spp. having
terbinafine MIC ≥ 1or <1 μg/mL (Group I-p = .712 and Group II-p = .69).
CONCLUSIONS: This study revealed that prolonging
terbinafine or itraconazole therapy for beyond 8 weeks rather than the standard 4 weeks significantly increases the cure rate. Moreover, no correlation has been observed between antifungal susceptibility and clinical outcomes. The MIC remains the primary parameter for defining antifungal activity and predicting the potency of antifungal agents against specific fungi. However, predicting therapeutic success based solely on the MIC of a fungal strain is not always reliable, as studies have shown a poor correlation between in vitro data and in vivo outcomes. To address this issue, further correlation of antifungal susceptibility testing (AFST) data with clinical outcomes and therapeutic drug monitoring is needed. It also highlights that initiation of the treatment within <6 months of illness increases cure rates and reduces recurrence. Extensive research is warranted to establish a better treatment regime for dermatophytosis.