几种抗真菌药物对马尔尼菲青霉的体外药敏试验

目的 观察马尔尼菲青霉（PM）广西野生银星竹鼠寄生株与临床人分离株对伏立康唑和几种常用抗真菌药物的敏感性。方法 采用美国临床实验室标准委员会（CLSI）M27-A2和M38-A方案中的微量稀释法,测定伏立康唑、伊曲康唑、特比萘芬、两性霉素B 及氟康唑对14株广西野生银星竹鼠PM寄生株与25株临床人PM分离株25 ℃菌丝相及37 ℃酵母相的最小抑菌浓度（MIC）。用两样本均数比较t检验比较PM寄生株与临床人PM分离株MIC的差异性,用配对t检验比较同一株菌在两种不同温度相下的MIC差异性。结果 伏立康唑、伊曲康唑、特比萘芬、两性霉素B、氟康唑对PM寄生株菌丝相的MIC分别为：0.0313 ～ 0.1250、0.1250 ～ 1.0000、0.0313 ～ 0.5000、0.2500 ～ 4.0000、2.0000 ～ 8.0000 mg/L;对PM寄生株酵母相的MIC分别为：0.0078 ～ 0.2500、0.0313 ～ 0.5000、0.0313 ～ 1.0000、0.2500 ～ 2.0000、1.0000 ～ 8.0000 mg/L;对PM临床人分离株菌丝相的MIC分别为：0.0313 ～ 0.2500、0.0625 ～ 1.0000、0.0313 ～ 1.0000、0.2500 ～ 4.0000、2.0000 ～ 32.0000 mg/L;对PM临床人分离株酵母相的MIC分别为：0.0039 ～ 0.2500、0.0313 ～ 0.5000、0.0313 ～ 2.0000、0.1250 ～ 2.0000、2.0000 ～ 16.0000 mg/L。5种抗真菌药物对广西野生银星竹鼠PM寄生株与临床人PM分离株菌丝相和酵母相均敏感。同一温度下伏立康唑对两种不同来源PM的MIC最低,其他药物的MIC依次为伊曲康唑、特比萘芬 < 两性霉素B < 氟康唑。同一药物在同一温度下对广西野生银星竹鼠PM寄生株与PM临床分离株的MIC无明显差异;伊曲康唑、两性霉素B、特比萘芬对同一菌株在菌丝相和酵母相下的MIC存在差异。结论 PM对伏立康唑的敏感性最高;来自于广西野生银星竹鼠的PM寄生株与临床人PM分离株对伏立康唑、伊曲康唑、特比萘芬、两性霉素B及氟康唑的MIC类似;菌相的改变可影响PM对伊曲康唑、两性霉素B、特比萘芬的敏感性。     

Clinical Evaluation of a New-Formula Shampoo for Scalp Seborrheic Dermatitis Containing Extract of Rosa centifolia Petals and Epigallocatechin Gallate: A Randomized,Double-Blind,Controlled Study

Background

Scalp seborrheic dermatitis is a chronic type of inflammatory dermatosis that is associated with sebum secretion and proliferation of Malassezia species. Ketoconazole or zinc-pyrithione shampoos are common treatments for scalp seborrheic dermatitis. However, shampoos comprising different compounds are required to provide patients with a wider range of treatment options.

Objective

This study was designed to evaluate a new-formula shampoo that contains natural ingredients-including extract of Rosa centifolia petals and epigallocatechin gallate (EGCG)-that exert antioxidative, anti-inflammatory, and sebum secretion inhibitory effects, and antifungal agents for the treatment of scalp seborrheic dermatitis.

Methods

Seventy-five patients were randomized into three treatment groups; new-formula shampoo, 2% ketoconazole shampoo, and 1% zinc- pyrithione shampoo. The clinical severity scores and sebum levels were assessed by the same dermatologists at baseline (week 0), and at 2 and 4 weeks after using the shampoo. User satisfaction and irritation were also assessed with the aid of a questionnaire.

Results

The efficacy of the new-formula shampoo was comparable to that of both the 1% zinc-pyrithione shampoo and the 2% ketoconazole shampoo. Furthermore, it was found to provide a more rapid response than the 1% zinc-pyrithione shampoo for mild erythema lesions and was associated with greater user satisfaction compared with the 2% ketoconazole shampoo. However, the new-formula shampoo did not exhibit the previously reported sebum inhibitory effect.

Conclusion

Extract of R. centifolia petals or EGCG could be useful ingredients in the treatment of scalp seborrheic dermatitis.     

Analysis of the antifungal activity of ketoconazole, zinc pyrithione, and ciclopirox olamine against Pityrosporum ouale. A diffusion assay for cultures in solid media

Background Recently dandruff has been associated with a local increment in the number of Pityrosporum yeasts. Due to this fact, several anti-dandruff shampoos containing antifungals have been marketed. Objective We studied the sensitivity of Pityrosporum ovale (PO) to three different groups of antimycotics (ketoconazole, Zn pyrithione, and ciclopirox olamine). Methods /Results The drugs were tested by an inhibition assay in solid medium. Ketoconazole proved to be the most effective drug in inhibiting PO growth in a dose-dependent fashion. The results of our evaluation revealed that the inhibitory effects of the drugs were ketoconazole > Zn pyrithione > ciclopirox olamine. Conclusion We postulate that the diffusion assay is a reliable medium for evaluating the effectiveness of antifungals contained in anti-dandruff shampoos.     

皮炎外瓶霉临床和环境分离株对6种常用抗真菌药物的敏感性测定

目的 探讨临床分离的皮炎外瓶霉对6种常用抗真菌药物的敏感性。方法 参考美国临床实验室标准化研究所M27-A2方案测定特比萘芬（TRB）、伊曲康唑（ITC）、两性霉素B（AMB）、氟康唑（FLC）、伏立康唑（VRC）及卡泊芬净（CAS） 对16株皮炎外瓶霉的最低抑菌浓度（MIC）,同时以E-test法测定VRC、ITC和AMB对16株皮炎外瓶霉的MIC,并进一步测定每种药物的最低杀菌浓度（MFC）。在此基础上,观察TRB与ITC及VRC联合应用时对皮炎外瓶霉的抗菌作用。结果 微量液基稀释法测得TRB、VRC、ITC、AMB、FLC和CAS 对皮炎外瓶霉MIC范围分别为：0.125 ~ 0.25、0.25 ~ 0.5、2.0、2.0、16 ~ 32和16 ~ 64mg/L;TRB、VRC、ITC、AMB和FLC的MFC范围分别为：0.125 ~ 0.5、0.25 ~ 0.5、2.0 ~ 4.0、2.0 ~ 4.0和16 ~ 64 mg/L。E-test法测定VRC、ITC和AMB的MIC范围为：0.032 ~ 0.094、0.047 ~ 0.5和0.125 ~ 3.0 mg/L。TRB与ITC及VRC在体外联合应用对皮炎外瓶霉无协同效应。结论 皮炎外瓶霉在体外对TRB、ITC、AMB、VRC敏感,对FLC和CAS不敏感。     

脓肿分枝杆菌临床分离株药物敏感性初探

目的:分析脓肿分枝杆菌临床分离株对常用抗生素的体外药物敏感性.方法:临床菌株分离自2019年9月至2021年6月就诊于陆军军医大学大坪医院皮肤科的脓肿分枝杆菌皮肤软组织感染患者,用微量肉汤稀释法检测其对克拉霉素、阿奇霉素、阿米卡星、莫西沙星、环丙沙星、米诺环素、美罗培南、利奈唑胺、异烟肼、利福平、头孢西丁的最小抑菌浓度...     

In vitro susceptibility testing of ciclopirox,terbinafine, ketoconazole and itraconazole against dermatophytes and nondermatophytes,and in vitro evaluation of combination antifungal activity

BACKGROUND: With the development of newer antifungal agents with activity against both yeasts and filamentous fungi, there is an increased need to develop and standardize in vitro assays that will evaluate the activity of antimycotics against filamentous fungi. In vitro analysis of antifungal activity of these agents would also allow for the comparison between different antimycotics, which in turn may clarify the reasons for lack of clinical response or serve as an effective therapy for patients with chronic infection. OBJECTIVES: To determine the in vitro susceptibility of fungal organisms to ciclopirox, terbinafine, ketoconazole and itraconazole and to evaluate the in vitro activity and mode of interaction of ciclopirox in combination with either terbinafine or itraconazole. MATERIALS AND METHODS: In the minimum inhibitory concentration (MIC) study 133 strains were evaluated, including dermatophytes (110 strains; 98 from Trichophyton spp.), Candida spp. (14 strains) and nondermatophyte moulds (nine strains). In vitro susceptibility testing was conducted in microbroth dilutions based on the National Committee for Clinical Laboratory Standards (NCCLS) M27-A proposed standard. The testing MIC ranges were 0.003-2 microg mL-1 for ciclopirox and terbinafine, and 0.06-32 microg mL-1 for itraconazole and ketoconazole. For inoculum preparation, dermatophytes were grown on Heinz oatmeal cereal agar slants. Inoculum suspensions of dermatophytes were diluted in RPMI 1640 (Sigma-Aldrich) with the desired final concentration being 2-5 x 103 c.f.u. mL-1. Once inoculated, the microdilution plates were set up according to the NCCLS M27-A method, incubated at 35 degrees C, and read visually following 7 days of incubation. For azole agents, the MIC was the lowest concentration showing 80% growth inhibition; for terbinafine and ciclopirox, the MIC was the lowest concentration showing 100% growth inhibition. In the synergy studies, 29 strains from nondermatophyte species were evaluated using a checkerboard microdilution method. The concentrations tested were: 0 and 0.06-32 microg mL-1 for itraconazole, and 0 and 0.003-4 microg mL-1 for both terbinafine and ciclopirox. Modes of interaction between drugs were classified as synergism, additivism, antagonism or indifference based on fractional inhibitory concentration index values (FIC index). Synergism was defined as an FIC index of < or = 0.50, additivity as an FIC index of < or = 1.0, and antagonism as an FIC index of > or = 2.0. The drug combination was interpreted as indifferent if neither of the drugs had any visible effect on the presence of the other drug. RESULTS: In the MIC study, the dermatophyte MIC values (microg mL-1) (mean +/- SEM) were: ciclopirox (0.04 +/- 0.02), terbinafine (0.04 +/- 0.23), itraconazole (2.28 +/- 7.42) and ketoconazole (0.83 +/- 1.99). The yeast MIC values (microg mL-1) (mean +/- SEM) were: ciclopirox (0.05 +/- 0.02), terbinafine (1.77 +/- 0.58), itraconazole (0.18 +/- 0.27) and ketoconazole (0.56 +/- 0.60). The non-dermatophyte fungi MIC values (microg mL-1) (mean +/- SEM) were: ciclopirox (1.04 +/- 2.62), terbinafine (1.04 +/- 0.95), itraconazole (17.87 +/- 16.75) and ketoconazole (10.69 +/- 13.09). In the synergy study, with ciclopirox in combination with terbinafine, mainly a synergistic or additive reaction was observed; there were no cases of antagonism. For ciclopirox in combination with itraconazole, there were some instances of additivism or synergism, with indifference in the majority of instances; there were no cases of antagonism. CONCLUSIONS: In vitro susceptibility testing indicates that ciclopirox may have a broad antimicrobial profile including dermatophytes, yeasts and other nondermatophytes. Terbinafine is extremely potent against dermatophytes. In vitro evaluation of activity of ciclopirox and terbinafine suggests many instances of synergy or additivism; for ciclopirox and itraconazole there may be indifference, synergy or additivism.     

念珠地丝菌对五种抗真菌药的体外敏感性及电镜观察

目的 探讨5种临床常见抗真菌药对念珠地丝菌的体外抑制作用,并观察用药后念珠地丝菌的形态学变化。方法 5种临床常见抗真菌药为特比萘芬、两性霉素B、氟胞嘧啶、氟康唑和伊曲康唑。参照美国国家临床试验标准委员会修订的M27?A2方案及相关文献,测定各药物对念珠地丝菌的MIC值。应用扫描电镜观察特比萘芬作用后念珠地丝菌的形态学变化。结果 5种药物对念珠地丝菌的MIC值依次为：特比萘芬0.01 μg/ml、两性霉素B 0.4 μg/ml、氟胞嘧啶2 μg/ml、氟康唑2.69 μg/ml、伊曲康唑 0.25 μg/ml。念珠地丝菌对特比萘芬、两性霉素B、氟胞嘧啶、氟康唑均敏感,对伊曲康唑为剂量依赖性敏感。扫描电镜可见,经特比萘芬作用后念珠地丝菌菌体表面出现粗糙、皱缩、不规则缺损及孔洞,甚至呈碎片状。结论 特比萘芬对念珠地丝菌的抗菌活性最显著,在一定范围内,特比萘芬浓度越高,念珠地丝菌被破坏的程度越严重。     

In vitro activity of the lipopeptide derivative (Pal-lys-lys-NH2), alone and in combination with antifungal agents, against clinical isolates of dermatophytes

Background  An increasing number of antimycotics have become available for the treatment of dermatophytoses; however, there are reports suggesting recalcitrance to therapy or resistance of a dermatophyte against conventional treatment. Lipopeptides represent novel therapeutic drugs with a new mode of action.
Objectives  The aim of this study was to investigate the in vitro effects of the lipopeptide Pal-Lys-Lys-NH₂ (PAL) alone and in combination with standard antifungal agents, such as fluconazole (FLU), itraconazole (ITRA) and terbinafine (TER) against 24 clinical isolates of dermatophytes belonging to four species.
Methods  A broth microdilution method following the Clinical and Laboratory Standards Institute recommendations (M38-A) was used for testing drugs alone and in combination.
Results  PAL minimum inhibitory concentrations (MICs) ranged from ≤ 0·25 to > 16 μg mL⁻¹ and they were similar to those of FLU and higher than those of either ITRA or TER. Synergy, defined as a fractional inhibitory concentration (FIC) index of ≤ 0·50, was observed in 67%, 52% and 15% of PAL/ITRA, PAL/TER and PAL/FLU interactions, respectively. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination.
Conclusions  Our study demonstrates that PAL has potential activity against dermatophytes. In addition, the in vitro activity of PAL can be enhanced upon combination with standard drugs. This lipopeptide applied in the form of lacquer, spray or ointment, could represent an interesting new therapy, particularly when combined with conventional treatment in recalcitrant or resistant dermatophyte infections.