Susceptibilidad in vitro a antifúngicos de especies de Cándida / In vitro antifungal susceptibility of Candida spp

Resumen Objetivo. Analizar la susceptibilidad in vitro de aislamientos de Candida spp. provenientes de onicomicosis obtenidos entre 2016 y 2019, para contribuir con el conocimiento sobre la necesidad o no de realizar pruebas de susceptibilidad a los microorganismos aislados antes de prescribir el tratamiento. Métodos. El estudio consistió en identificar 23 aislamientos de Candida spp. utilizando el sistema automatizado Vitek2® (bioMérieux, Francia). Se determinó la susceptibilidad in vitro de estos aislamientos ante dos antifúngicos tópicos (amorolfina y ciclopirox) y dos antifúngicos sistémicos (fluconazol e itraconazol) por el método de microdilución en caldo M27-A3 del Instituto Estándares para el Laboratorio Clínico (CLSI por sus siglas en inglés) de los Estados Unidos de América. Resultados. La mayoría de los aislamientos correspondieron a Candida parapsilosis (34,8 %), seguido por C. albicans (30,3 %), C. guilliermondii (17,4 %), C. tropicalis (8,7 %), C. dubliniensis (4,4 %) y C. krusei (4,4 %). No se encontraron diferencias estadísticamente significativas entre las CIMs de los diferentes antifúngicos y en promedio hubo susceptibilidad para todos los antifúngicos analizados. Sin embargo, para fluconazol se encontró un aislamiento con CIM alta de C. guilliermondii y un aislamiento resistente de C. parapsilosis. Conclusiones. Las directrices internacionales recomiendan pruebas de susceptibilidad para Candida spp. de hemocultivos o tejidos tras infecciones sistémicas. En todas las demás candidiasis se identifica la especie y se revisan sus patrones de susceptibilidad en la literatura. Por lo tanto, es de importancia conocer que aislamientos de onicomicosis de Candida no-albicans, especialmente de C. guilliermondii y C. parapsilosis, presentan una susceptibilidad disminuida a ciertos antifúngicos que se utilizan como tratamiento, por lo que se recomienda realizar pruebas de susceptibilidad en caso de no tener una buena respuesta al tratamiento en casos de onicomicosis por estas levaduras.

Abstract Aim. The purpose of this investigation was to determine the in vitro susceptibility patterns of Candida spp. isolated from onychomycosis, in order to contribute with strategies for optimal clinical laboratory management of patients with onychomycosis infected with these yeasts. Methods . A total of 23 isolates of Candida spp. were identified with the automatized system Vitek®2 (system bioMérieux, France). In vitro susceptibility patterns were evaluated with two topic antifungals (amorolfine and ciclopirox) and two systemic antifungals (fluconazole and itraconazole) using the Clinical Laboratory and Standards Institute (CLSI) broth microdilution M27-A3 guidelines. Results . Most of the isolates were identified as Candida parapsilosis (34,8 %), followed by C. albicans (30,3 %), C. guilliermondii (17,4 %), C. tropicalis (8,7 %), C. dubliniensis (4,4 %) and C. krusei (4,4 %). There were no statistically significant differences among the MICs of the antifungals tested. However, there was one isolate of C. guilliermondii with high MIC for fluconazole and one fluconazole resistant isolate of C. parapsilosis. Conclusions. Susceptibility tests are only recommended internationally for Candida spp. isolated from blood stream or tissue in systemic infections. In every other candidiasis there is only a species identification, while its susceptibility pattern for treatment is reviewed in literature. Therefore, it is important to report that Candida no-albicans isolates from onychomycosis, especially C. guilliermondii and C. parapsilosis, have a reduced susceptibility to some antifungals commonly used for treatment. According to the obtained in vitro results, we recommend performing antifungal susceptibility testing in those cases of onychomycosis caused by Candida spp. no responsive to treatment.

A randomized, double-blind trial of amorolfine 0.25% cream and sertaconazole 2% cream in limited dermatophytosis

Background: Dermatophytosis is becoming increasingly unresponsive to conventional antifungals. Newer topical antifungals may be more effective in these patients. Aims: To evaluate and compare the efficacy and safety of amorolfine 0.25% cream and sertaconazole 2% cream in limited tinea cruris/corporis. Methods: A single-center, randomized (1:1), double-blind, parallel group, active-controlled trial (CTRI/2014/12/005246) was performed. Sixty-six untreated adults with acutely symptomatic tinea cruris/corporis were included in the study. All patients had limited cutaneous involvement and were KOH mount positive. Group A received amorolfine 0.25% cream, and group B received sertaconazole 2% cream twice daily application to the lesions for 4 weeks. After the baseline visit, four follow-up visits were carried out. The outcome measures for effectiveness were clinical and mycological cure. Safety parameters studied were treatment-emergent adverse events and changes in routine laboratory parameters. Results: Both sertaconazole and amorolfine significantly reduced symptoms (P < 0.001) in both groups. However, improvement in symptoms (pruritus, burning sensation, erythema, scaling and crusting) was significantly greater in the sertaconazole group at every follow-up visit. Sertaconazole cream was also more effective than amorolfine cream in reducing the number of lesions (P = 0.002 at 12 weeks) and improving the Dermatology Life Quality Index (P < 0.001) at all the follow-up visits. Adverse events were similar in the two groups (P = 0.117). Fungal cultures became negative in 92.3% of the sertaconazole group as compared to 80% in the amorolfine group (P = 0.010). Limitations: Antifungal susceptibility testing could not be done. Conclusion: Sertaconazole 2% is superior to amorolfine 0.25%, both in terms of effectiveness and tolerability. Improvement can be appreciated from second week onwards.

Clinical Efficacy of Long-pulsed 1064 nm Laser Combined with Amorolfine Hydrochloride in the Treatment of Patients with Onychomycosis / 中国药师

Objective:To investigate the clinical efficacy of long-pulsed 1064nm laser combined with amorolfine hydrochloride in the treatment of patients with onychomycosis. Methods:Totally 106 cases of patients with onychomycosis were randomly divided into the observation group (n=53) and the control group(n=53) according to the random number table. The control group was given 5%amorolfine hydrochloride liniment, while the observation group was treated with long-pulsed 1064nm laser additionally. The course of treatment was 6 months. The clinical efficacy, length of deck in ward areas, length of deck in health zone, clearance of mycology and adverse reactions were compared between the groups. Results:The total effective rate of the observation group(90. 57%) was signifi-cantly higher than that of the control group(75. 47%, P<0. 05). After the treatment, the length of deck in ward areas in both groups were significantly decreased, while the length of deck in health zone were significantly increased (P<0. 05). The length of deck in ward areas in the observation group was significantly lower than that in the control group, while the length of deck in health zone was significantly higher than that in the control group(P<0. 05). The clearance rate of mycology in the observation group (86. 79%) was significantly higher than that in the control group (67. 92%, P<0. 05). There were no serious adverse reactions during the treatment course. Conclusion:Long-pulsed 1064nm laser combined with 5% amorolfine hydrochloride liniment in the treatment of patients with onychomycosis has remarkable, safe and reliable clinical effects, which shows important study value.

Experience of Combination Treatment of Toenail Onychomycosis with Oral Itraconazole and Topical 5% Amorolfine Nail Lacquer / 대한의진균학회지

BACKGROUND: Target of oral itraconazole is nail matrix via nail bed diffusion. On the contrary, topical amorolfine directly acts on nail plate through a transungual drug delivery system. When this combination treatment of oral itraconazole and topical amorolfine nail lacquer is applied for onychomycosis, we may expect their synergistic effects. OBJECTIVE: We will discuss our clinical experiences of 78 patients in Chung Ang University hospital about combination treatment of onychomycosis with oral itraconazole and topical 5% amorolfine nail lacquer. METHODS: We treated 135 toenail onychomycosis patients (M/F=79/56) from January 2001 to April 2004. But, among 135 patients, we analyzed only 78 (57.8%) patients (M/F=46/32) treated by combination treatments composed of twice weekly application of topical 5% amorolfine nail lacquer and 3 pulse therapy of oral itraconazole. Efficacies of treatment are composed of clinical cure based on decrement of affected nail area by digital camera recording and mycological cure based on KOH exam, and fungus cultures on after 6 months. RESULTS: Distribution of patients by clinical types is as follows; distal subungual onychomycosis (DSO) : 68 patients (87.2%), whitish superficial onychomycosis (WSO) : 4 patients (5.1%), and total dystrophic onychomycosis (TDO) : 6 patients (7.7%). Reduction rates of affected area by clinical types are DSO: 85.1%, WSO: 83.1%, and TDO: 70.3%. Isolated strains from the fungal culture are T. rubrum: 67 (85.9%), T. mentagrophytes: 5 (6.4%), and Candida spp.: 6 (7.7%). Reduction rate of affected nail area (75.0%) in patients with diabetes mellitus is significantly reduced comparing with that (80.8%) of patients without associated disease. The total reduced rate of affected nail area and cure rate are 81.5%, and 57.4% respectively. CONCLUSION: Oral itraconazole and topical amorolfine nail lacquer combination therapy will be a promising treatment modality for onychomycosis.

Hyperpigmentation Due to the Overuse of Amorolfine Nail Lacquer / 대한의진균학회지

Amorolfine is a broad-spectrum antimycotic agent, inhibiting biosynthesis of ergosterol. It penetrates rapidly into the nail after topical application by transungual drug delivery system. Although it is considered to be relatively stable chemical substances, it may cause nail discoloration by excessive topical application and prolonged sun exposure. We report a case of toenail hyperpigmentation due to the overuse of amorolfine nail lacquer, which is the first report in Korea.

Hyperpigmentation Due to the Overuse of Amorolfine Nail Lacquer / 대한의진균학회지

Amorolfine is a broad-spectrum antimycotic agent, inhibiting biosynthesis of ergosterol. It penetrates rapidly into the nail after topical application by transungual drug delivery system. Although it is considered to be relatively stable chemical substances, it may cause nail discoloration by excessive topical application and prolonged sun exposure. We report a case of toenail hyperpigmentation due to the overuse of amorolfine nail lacquer, which is the first report in Korea.

Amorolfine Nail Lacquer 5 % Once Weekly in Onychomycosis of Fingers and / or Toes / 대한피부과학회지

BACKGROUND: Amorolfine is a new topical antifungal drug of the morpholine class has broad spectrum fungicidal activity. Amorolfine nail lacquer 5% is a transungual delivery system which can penetrate well through the nail plate to the infected keratin and remain there for a prolonged period. OBJECTIVE: The aim of this study is to assess the efficacy and tolerability of 5% amorolfine nail lacquer given once weekly to the patients with onychomycosis. METHODS: 29 patients with onychomycosis affecting not more than 80% of the surface of nail were treated once weekly for up to 9 months with amorolfine nail lacquer 5%. Clinical and mycological examination were performed before treatment and 3, 6, 9 months after start of treatment. Final evaluation was done 3 months after the end of treatment. RESULTS: Average affected area(%) and average score of clinical signs-thickening, splitting, discoloration-were significantly decreased 3 months after start of treatment. Mycological cure rate was continuously increased according to the treatment duration reaching 75.9% at 3 months after treatment. Overall efficacy assessed by the investgators were cure in 31.0% and improvement in 41.4%. Tolerability, mode and frequency of treatment, and formulation were evaluated as good or excellent by most of the patients.No systemic or local side effect was observed. CONCLUSION: Amorolfine nail lacquer 5% used once weekly up to 9 months was relatively effective and safe for the treatment of onychomycosis.