drug susceptibility and resistance of fungal isolates in onychomycosis against efinaconazole

P7037Disseminated mucormycosis

Ha Do, MD, MS, Indiana University, Dermatology Department, Indianapolis, IN,United States; Lori Sanford, MD, Indiana University, Dermatology Department,Indianapolis, IN, United States; Yongxue Yao, MD, PhD, Indiana University,Dermatology Department, Indianapolis, IN, United States

We present a case of a 55-year-old man with a history of metastatic pancreaticneuroendocrine tumor statusepost-multivisceral (liver, stomach, pancreas, andintestine) transplant in March 2011. He subsequently developed hepatic EBV-associated monomorphic posttransplant lymphoproliferative disorder in June 2011and was treated with 4 cycles of weekly Rituxan. He was admitted in February 2012for severe dyspnea related to persistent pancytopenia since transplant. During thishospitalization, the patient developed a 4-day history of generalized tender rashassociated with arthralgia. Examination revealed multiple tender erythematous,indurated dermal nodules, some with central dusky erosions, on the trunk andextremities. Skin biopsy showed large fungal hyphae and spores in the dermis.Fungal morphology evaluation and skin tissue culture confirmed mucormycosisspecies. Pan-CT imaging showed multifocal cutaneous and paranasal involvement.Ambisome and micafungin were initiated for disseminated mucormycosis. Heunderwent several surgical debridements in addition to medical therapy.Mucormycosis is a rare fungal infection that often occurs in diabetics, chronic renalfailure patients, or immunosuppressed population such as leukemia, lymphoma,AIDS, burns, and organ transplant patients. The clinical course is acute with rapiddeterioration and associated with high mortality rate up to 80%. All 5 major clinicalforms (cutaneous, rhinocerebral, pulmonary, gastrointestinal, and disseminated) arecharacterized by blood vessel invasion which leads to tissue infarction and necroticpurulent eschar.

AB128

cial support: None identified.

P6538Drug susceptibility and resistance of fungal isolates in onychomycosisagainst efinaconazole

William Jo, PhD, Dow Pharmaceutical Sciences (a division of ValeantPharmaceuticals International), Petaluma, CA, United States; Atsushi Iwata, MS,Kaken Pharmaceutical Co Ltd, Kyoto, Japan; Hisato Senda, DVM, KakenPharmaceutical Co Ltd, Kyoto, Japan; Takashi Nakamura, MS, KakenPharmaceutical Co Ltd, Tokyo, Japan

Background: Efinaconazole 10% solution is a new triazole antifungal in developmentfor topical treatment of onychomycosis. Many antifungals have been widely used formycoses with inherent drug resistance concerns. However, few studies assess thepotential for drug resistance in onychomycosis therapy.

Objective: To investigate in vitro susceptibility of onychomycosis clinical isolatesagainst efinaconazole and their potential to develop drug resistance.

Methods: The in vitro susceptibility to efinaconazole was determined for isolatesrecovered in 2 multicenter, vehicle-controlled onychomycosis clinical studies withtopical efinaconazole 10% solution, using the broth micro dilution minimuminhibitory concentration (MIC) assay (CLSI M38-A2). Isolates were from theUnited States, Canada and Japan collected at screening (N¼ 1498), end of treatment(N ¼ 45, week 48) and follow-up (N ¼ 121, week 52) visits. The potential ofdermatophytes acquiring resistance to efinaconazole was also examined in vitrowith serial subculturing of 6 T rubrum strains and 1 T mentagrophytes strain in thepresence of subinhibitory efinaconazole concentrations for 10-12 passages. TheMICwas determined for each strain before the first passage and after each passage tomonitor changes in MIC.

Results: The species distribution of isolates at screening included T rubrum (N ¼1387, 92.6%) T mentagrophytes (N ¼ 106, 7.1%), and Epidermophyton floccosum(N ¼ 5, 0.3%). The efinaconazole MICs against T rubrum and T mentagrophyteswere # 0.002-0.03 and # 0.002-0.06 �g/mL, respectively. Only 3 and 10 T rubrumisolates were recovered from efinaconazole 10% solution treatment arms at weeks48 and 52, respectively (MIC # 0.002-0.015 �g/mL). After serial subculturing withefinaconazole, only 2 T rubrum and 1 T mentagrophytes strains exhibited a 2- to 4-fold increase in MIC. The MIC increases were similar to those observed withitraconazole and clotrimazole.

Conclusion: Efinaconazole demonstrated potent antifungal activity within a narrowrange of MICs in recently-collected dermatophyte isolates from onychomycosispatients from different geographical locations. The MICs for T rubrum isolatesrecovered were within the screening MIC range. No significant increases in MICwere observed in T rubrum and T mentagrophytes strains after serial subculturing.These data suggest that the potential of dermatophytes developing resistance toefinaconazole in onychomycosis therapy is low.

nsored by Valeant Dermatology a division of Valeant Pharmacerica LLC.

100% spo euticalsNorth Am

J AM ACAD DERMATOL

P6794Feline sporotrichosis: Family case report

Lily Paola Belmonte Casta~neda, MD, Policlinica Geral Do Rio de Janeiro, Rio deJaneiro, Brazil; Glaura Plata, MD, Policlinica Geral Do Rio de Janeiro, Rio deJaneiro, Brazil; Marcos Vinicius Lima Galles, MD, Policlinica Geral Do Rio deJaneiro, Rio de Janeiro, Brazil; Mayra Alejandra Carillo Uribe, MD, PoliclinicaGeral Do Rio de Janeiro, Rio de Janeiro, Brazil; M�onica Daniela Gauto Nu~nez, MD,Policlinica Geral Do Rio de Janeiro, Rio de Janeiro, Brazil

Sporotrichosis is described as a disease of low incidence in Brazil; however, recentreports show that the state of Rio de Janeiro has been the scene of an urban epidemicarea. In this especificy area, cases have been reported related to scratch or bite ofdomestic animals (dogs, cats), leading to family outbreaks, affecting individuals of allages and sex, becoming an emerging zoonosis and thus a public health problem dueto the significant increase in cases. With the increased incidence, also increases theincidence of severe clinical forms or atypical form of the disease. Case 1: Female, 14years, born and raised in Rio de Janeiro, presenting 20 days ago, ulcerated lesion inthe left malar region, with the later onset of other painful and erythematous nodulesin the same lymph hemiface following the path. Reported a scratch by a domesticcat. Culture: isolated Sporothrix schenckii. Histopatologic: pseudoepitheliomatoushyperplasia of the epidermis, dermis with marked mononuclear cell infiltration, andgiant cell granulomatous reaction multinucleadas. Treatment: Itraconazole 100 mgdaily, with complete resolution of lesions in one month. Case 2: Patient, 45 years,mother and resident of the same household, housewife. Report that 1 month afterdomestic cat scratch, she presented ulcerated nodules in the proximal portion of theright leg, later had smaller lesions on thigh of the same limb, following the lymphaticpath. Culture: isolated Sporothrix schenckii. Histopatologic: granulomatous, epi-thelioid histiocytes, multinucleated giant cells and necrose. Treatment: Itraconazole100 mg daily and thermotherapy, progressing to healing of lesions in 2 months. Theoccurrence of sporotrichosis and increased incidence in the metropolitan area ofthe state, is strongly related to social, environmental, and behavioral factors thatinfluence their frequency, transmission, and geographic distribution. This strainshave slightly different characteristics of the strains studied in Spain and S~ao Paulo.We need further studies to determine the epidemiologic and social transcendence ofhuman sporotrichosis in the state of Rio de Janeiro, perhaps it is necessary toimplement this as a state and municipal reportable disease.

cial support: None identified.

P6481Juvenile form of paracoccidioidomycosis associated with exuberanthypoalbuminemia

Adriana T�aquez Munoz, Policl�ınica Geral do Rio de Janeiro, Rio de Janeiro, Brazil;Aline Sarkis dos Santos, Policl�ınica Geral do Rio de Janeiro, Rio de Janeiro, Brazil;Antonio Francesconi do Valle, Fundac~ao Oswaldo Cruz (FIOCRUZ), Rio deJaneiro, Brazil; Carlos Alberto Cer�on, Policl�ınica Geral do Rio de Janeiro, Rio deJaneiro, Brazil; Ludimila Noleto de Rezende, Policl�ınica Geral do Rio de Janeiro,Rio de Janeiro, Brazil; Raquel Noschang Pereira, Policl�ınica Geral do Rio deJaneiro, Rio de Janeiro, Brazil

Background: Paracoccidioidomycosis (PCM) is a suppurative and granulomatoussystemic mycosis caused by thermodimorphic Paracoccidioides brasiliensis (Pb)fungus. It is shown in the following clinical forms: chronic adult (90%) and juvenile(10%).

Case report: Male patient, 26 years, farmer, showed multiple lymphadenopathyduring 8 months, bilateral, in the cervical, axillary and inguinal regions, and alsonodular lesions on the face and ulceration in the groin, associated to afternoon fever,anorexia and weight loss. Exams: Serology for fungi: non-reactive, direct mycologicexamination and culture of lymph node aspirated: positive for Pb, lymph nodebiopsy: paracoccidiodiomicose, albumin: 1.8 (hypoalbuminemia). Evolution:Started the treatment with itraconazole 200 mg/day, showing improvement onthe skin lesions but with significant lymphedema of the penis, scrotum, pubicregion, and lower limbs. Was treated with corticosteroids but without improve-ment. Only after 5 months showed gradual clinical improvement and results in theedema with antifungal medication and oral protein replacement.

Discussion: The PCM runs with great clinical polymorphism and the lymph nodesare the organsmost frequently involved in the juvenile form, as seen in this case. Thehypoalbuminemia affects great part of the patients, especially in the juvenile form,what can interfere in the clinical course and in the treatment response. The patienthad a very important protein calorie depletion, which was responsible for theedema and only relented with spare protein. The double immunodiffusion test is themost used in diagnosis because of its ease execution and high sensitivity andspecificity; however, it may have false-negative results, being significantly higher injuvenile clinical form, which is what happened with this patient. The treatment ofPCM juvenile type can be done with Itraconazole, trimethoprim + sulfamethoxa-zole, and in malabsorptive syndrome case it shall be used intravenous medication(amphotericin B). Drug combinations can also be used, because of the lowresponses from the use of only one drug. In patients with PCM it is used the term‘‘apparent cure or clinical cure’’ because of the impossibility of Pb eradication, andthe potential risk of a late revival. After the treatment, patients should be monitoredonce a year, during three years, at least, with clinical, radiologic, and serologicexaminations.

cial support: None identified.

APRIL 2013