Oral Itraconazole Treatment Research Articles

When cat rescue fails — Part 1. Lion-clip shaving, enilconazole bathing and oral itraconazole treatment failed to control an iatrogenic Microsporum canis outbreak in a shelter: but a novel ophytrium-chlorhexidine shampoo and mousse treatment succeeded in the home

OBJECTIVE: To identify the reason(s) for failure to prevent repeated nosocomial dermatophyte infection of shelter cats and to present alternative strategies which are less stressful to the cats and humans involved. ANIMALS: The Dorset branch of the Royal Society for the Prevention of Cruelty to Animals (RSPCA) seized 30 of 32 Persian cats from a cat breeder on the 2nd of August 2019 and put them into Ashley Heath RSPCA shelter. Two cats and three dogs were left at home. All 30 cats were returned to their guardian in July 2020. Three cats died between 2020 and 2022, leaving 29 cats which were seized on the 8th of March 2022 and put into two RSPCA shelters. The dogs were not seized. Four cats were later euthanased. METHODS: RSPCA Animal Treatment Reports along with photographs used for evidence in the court case against the breeder and the veterinary records of their primary veterinary surgeon were retrospectively reviewed. RESULTS: Clinical signs of dermatophytosis occurred on the index_ _case one week after dematting with clippers in August 2019. _Microsporum canis_ (_M. canis) _was cultured from 27 of 30 (90%)_ _cats on the 39th day of the Ashley Heath shelter stay in 2019. _M. canis_ infection could only have been acquired while in RSPCA care because the incubation period from infection to development of clinical signs for _M. canis_ is one to three weeks, and there was no history of ringworm in their home. Efforts to control the ringworm outbreak in the shelter included lion clipping, weekly enilconazole bathing and oral itraconazole (EI treatment) for five or seven weeks until culture negative. Six cats became culture positive again in 2020. Cats were housed in pairs in 2019 to 2020 and singly in 2022, therefore transmission was indirect (i.e. via fomites). Two cats remained positive when the cats were returned to their guardian in 2020, all 30 were treated with a single ophytrium-chlorhexidine (Douxo S3 Pyo) shampoo followed by ophytrium-chlorhexidine mousse rubbed into their fur for three weeks. It was reasonable to conclude that the ophytrium-chlorhexidine treatment had cleared the _M. canis_ infection for the following six reasons: first no cat developed clinical signs of dermatophytosis during the 20 months in their home. Second, no obvious ringworm lesions were seen on the photographs taken for evidence and third, no veterinary surgeon noted in the records any lesions suspicious of dermatophytosis during the examination of the cats within days of them being seized again in March 2022. Fourth: no positive dermatophyte results were produced as evidence during the trial (ringworm charges against the owner were dropped). Fifth: three of four dermatophyte tests performed on EI untreated cats were negative and samples from the positive cat were after three months in the shelter. Sixth: no EI treatment was administered until the cats had been in the shelters again for two and a half months. Nevertheless, shelter staff assumed ringworm infection from the arrival of the cats in 2022 and again subjected them to the stressful shaving/bathing/itraconazole protocol. CLINICAL RELEVANCE AND CONCLUSIONS: This is the first report of ophytrium-chlorhexidine for treatment and prevention of _M. canis _in cats. We recommend shelter staff be trained in basic barrier nursing and be educated regarding the difference between true dermatophyte infection versus fomite carriage.

The efficacy of oral itraconazole in the treatment of otomycosis accompanied by a perforated tympanic membrane

: Managing otomycosis in patients with an existing tympanic membrane perforation can pose challenges. However, this study underscores the efficacy of oral itraconazole as a viable treatment option for such instances.The research encompassed 34 individuals experiencing both otomycosis and a perforated tympanic membrane. These participants received a combination of oral itraconazole and antibiotic ear drops as treatment. Over a period of six weeks, their progress was monitored to assess the treatment's effectiveness and to observe any potential instances of recurrence.Out of the total 34 subjects examined in the study, 25 individuals achieved complete recovery after just one week of oral itraconazole treatment. Among the remaining 9 patients, 6 experienced a successful resolution of the condition following two weeks of therapy. For 3 patients, an extended treatment duration was required, and in a singular case, a recurrence of the condition was observed at the six-week mark.Oral itraconazole treatment presents as an efficacious substitute for conventional approaches in addressing otomycosis accompanied by tympanic membrane perforation.

Blastomycosis: A Review of Mycological and Clinical Aspects.

Blastomycosis is caused by a thermally dimorphic fungus that thrives in moist acidic soil. Blastomyces dermatitidis is the species responsible for most infections in North America and is especially common in areas around the Great Lakes, the St. Lawrence Seaway, and in several south-central and southeastern United States. Other Blastomyces species have more recently been discovered to cause disease in distinct geographic regions around the world. Infection almost always occurs following inhalation of conidia produced in the mold phase. Acute pulmonary infection ranges from asymptomatic to typical community-acquired pneumonia; more chronic forms of pulmonary infection can present as mass-like lesions or cavitary pneumonia. Infrequently, pulmonary infection can progress to acute respiratory distress syndrome that is associated with a high mortality rate. After initial pulmonary infection, hematogenous dissemination of the yeast form of Blastomyces is common. Most often this is manifested by cutaneous lesions, but osteoarticular, genitourinary, and central nervous system (CNS) involvement also occurs. The diagnosis of blastomycosis can be made by growth of the mold phase of Blastomyces spp. in culture or by histopathological identification of the distinctive features of the yeast form in tissues. Detection of cell wall antigens of Blastomyces in urine or serum provides a rapid method for a probable diagnosis of blastomycosis, but cross-reactivity with other endemic mycoses commonly occurs. Treatment of severe pulmonary or disseminated blastomycosis and CNS blastomycosis initially is with a lipid formulation of amphotericin B. After improvement, therapy can be changed to an oral azole, almost always itraconazole. With mild to moderate pulmonary or disseminated blastomycosis, oral itraconazole treatment is recommended.

P317 Phaeohyphomycosis caused by Phialophora verrucosa in a patient with CARD9 mutations

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectivesTo study an intractable case of phaeohyphomycosis caused by Phialophora verrucosa and the underlying genetic and immunological mechanisms.MethodsClinical and laboratory findings of the patient were studied. The patient's DNA was sequenced for CARD9. Innate and adaptive immunological responses of patient-derived PBMCs were evaluated with ELISA and flow cytometry.ResultsA 29-year-old Chinese male, born to nonconsanguineous parents, developed an enlarging plaque on his right anterior tibia at 25 years and underwent a 15-month treatment of oral itraconazole at the local hospital. Upon discontinuation of the medication, the plaque spread over his face, upper limbs, and back. Physical examination indicated dark brown verrucous plaques and nodules with surface ulcers and scabs on his right leg, upper limbs, and face. Skin biopsy revealed pigmented yeast cells with budding and yeast cell chain in the dermis. Based on tissue culture, we identified P. verrucosa as the causative pathogen, which was further validated by ITS, BT, and TEF gene sequencing. Thus, subcutaneous phaeohyphomycosis was diagnosed, and itraconazole combined with amphotericin B was prescribed. The lesions improved only marginally. We, therefore, gave him oral posaconazole instead, based on in vitro antifungal susceptibility results. After 1 month of posaconazole treatment, the serum BG assay value decreased and the lesions improved markedly.Based on previous reports linking CARD9 deficiency to phaeohyphomycosis, as well as early onset and recalcitrance characters, Sanger sequencing was performed in this patient and identified two compound heterozygous mutations in exon 6 (R373P) and exon 8 (D274GfsX60) of CARD9. We then evaluated the functional effect of the CARD9 mutations by assessing the stimuli-dependent release of proinflammatory cytokines and helper T cell differentiation. Cytokine production was markedly impaired in PBMCs post 24 h of stimulation with LPS, curdlan, TDB, mannan, MDP, β‐glucan, and various fungal ligands. Moreover, the patient showed a significant absence in Th22 and Th17 cell proportions, as well as lower IL-17A and IL-22 production after six days of co-incubation with the stimuli mentioned above.ConclusionOur report highlighted that otherwise healthy patients diagnosed with early-onset, unexplained, and recalcitrant phaeohyphomycosis should be analyzed for CARD9 mutations and immune deficiency. Furthermore, posaconazole may be an alternative worth trying after the failure of other antifungals due to its ideal results achieved in our case.

COVID-19 associated with disseminated histoplasmosis in a kidney transplant patient

We report a case of disseminated histoplasmosis and COVID-19 infection in a renal transplant recipient in Argentina. The patient exhibited respiratory symptoms, and a chest computed tomography scan (CT) showed multiple bilateral centrilobular opacities with a tree-in-bud pattern in both lobes. The patient was initially treated as having bacterial community-acquired pneumonia, and then tuberculosis. A month later, histoplasmosis was diagnosed, and Histoplasma capsulatum LAmB clade was isolated from sputum, skin and oral lesions. The patient was hospitalized and treatment was started with intravenous liposomal amphotericin B. During the course of the antifungal therapy the respiratory symptoms worsened, a new chest CT showed a unilateral lesion with a ground glass appearance and SARS-CoV-2 was detected in a new nasopharyngeal sample. In addition, plasma therapy was administered, and the immunosuppressive regimen was adjusted (everolimus was interrupted, mycophenolate mofetil reduced, and meprednisone increased). Finally, the patient's progress was favorable and was discharged after five days on oral itraconazole treatment for histoplasmosis.

Topical treatment of mycotic rhinitis-rhinosinusitis in dogs with meticulous debridement and 1% clotrimazole cream: 64 cases (2007–2014)

OBJECTIVE To evaluate outcomes for dogs with mycotic rhinitis-rhinosinusitis (MRR) treated by meticulous debridement and topical application of 1% clotrimazole cream and investigate potential prognostic factors that could help predict whether 1 or multiple treatments would be needed for clinical resolution of the condition. DESIGN Retrospective case series. ANIMALS 64 dogs. PROCEDURES Medical records were reviewed to identify dogs treated for MRR by meticulous debridement and topical application of 1% clotrimazole cream. Signalment, clinical signs, previous treatments, CT findings, presence of unilateral or bilateral disease, predisposing factors, number and type of treatments, and complications were recorded. Outcome information was obtained from records or by telephone interview with owners. Association of selected factors with the number of treatments needed for clinical resolution was evaluated. RESULTS Clotrimazole was instilled via the trephination site (n = 42) or under endoscopic guidance (22). Thirteen dogs underwent a 5-minute flush with 1% clotrimazole solution prior to cream application, and 34 received adjunctive oral itraconazole treatment. The MRR was deemed resolved in 58 dogs, and clinical signs persisted in 1 dog. Five dogs died (2 of causes unrelated to MRR) ≤ 1 month after treatment. The first treatment was successful in 42 of 62 (68%) dogs; overall success rate was 58 of 62 (94%). No prognostic factors for the number of treatments needed to provide clinical resolution were identified. Seven dogs with reinfection were successfully retreated. CONCLUSIONS AND CLINICAL RELEVANCE Topical treatment by meticulous debridement and 1% clotrimazole cream application had results similar to or better than those described in other studies of dogs with MRR. Trephination or adjunctive itraconazole treatment did not influence the number of treatments needed for a successful outcome.

Effects of Combined Treatment With Arsenic Trioxide and Itraconazole in Patients With Refractory Metastatic Basal Cell Carcinoma.

Tumor resistance is an emerging problem for Smoothened (SMO) inhibitor-treated metastatic basal cell carcinoma (BCC). Arsenic trioxide and itraconazole antagonize the hedgehog (HH) pathway at sites distinct from those treated by SMO inhibitors. To determine whether administration of intravenous arsenic trioxide and oral itraconazole in patients with metastatic BCC is associated with a reduction in GLI1 messenger RNA expression in tumor and/or normal skin biopsy samples. Five men with metastatic BCC who experienced relapse after SMO inhibitor treatment underwent intravenous arsenic trioxide treatment for 5 days, every 28 days, and oral itraconazole treatment on days 6 to 28. Data were collected from April 10 to November 14, 2013. Follow-up was completed on October 3, 2015, and data were analyzed from June 5 to October 6, 2015. The primary outcome was the change in messenger RNA levels of the GLI family zinc finger 1 (GLI1) gene (HH-pathway target gene) in biopsy specimens of normal skin or BCC before and after treatment. Secondary objectives were evaluation of tumor response and tolerability. Of the 5 patients (mean [SD] age, 52 [9] years; age range, 43-62 years), 3 completed 3 cycles of treatment and 2 discontinued treatment early owing to disease progression or adverse events. Adverse effects included grade 2 transaminitis and grade 4 leukopenia with a grade 3 infection. Overall, arsenic trioxide and itraconazole reduced GLI1 messenger RNA levels by 75% from baseline (P < .001). The best overall response after 3 treatment cycles was stable disease in 3 patients. Targeting the HH pathway with sequential arsenic trioxide and itraconazole treatment is a feasible treatment for metastatic BCC. Although some patients experienced stable disease for 3 months, none had tumor shrinkage, which may be owing to transient GLI1 suppression with sequential dosing. Continuous dosing may be required to fully inhibit the HH pathway and achieve clinical response.

Successful treatment of oral itraconazole for infantile hemangiomas: a case series.

Infantile hemangiomas can present a therapeutic challenge to clinicians, especially when associated with severe pain and feeding difficulties. The standard therapeutic management includes corticosteroids and propranolol. However, the clinical response is not always satisfactory. We present six cases of infantile hemangiomas successfully treated with oral itraconazole approximately 5mg/kg per day. In the first month, the red color of the lesions became a little lighter and the growth of the lesions was controlled in all cases. An obvious clinical improvement was noted in all cases during the 3-month period, with 80-100% improvement in each patient at the end of the treatment, which was judged by both their parents and the dermatologists. Compliance with treatment instructions of oral itraconazole in infants was judged to be very good. Side-effects were mild and limited. Although itraconazole can inhibit angiogenesis and tumor growth in vitro and in vivo associated with some cancers, further research is required to understand the pathogenesis of infantile hemangiomas and the mechanism of itraconazole.

Laryngeal histoplasmosis: an occupational hazard

Isolated laryngeal histoplasmosis is a very rare entity. It has variable clinical presentations that might mimic both benign and malignant lesions, and is usually associated with pulmonary and other disseminated forms of histoplasmosis. Herein, we report a case of primary laryngeal histoplasmosis without the involvement of other systems in a 70-year-old Chinese man, who previously worked as a miner. He presented with a history of hoarseness for two months, with no other associated symptoms. Direct laryngoscopy revealed irregularity of the posterior one-third of both vocal folds. Histopathological examination revealed the presence of Histoplasma capsulatumon periodic acidSchiff and Grocott's methenamine silver staining. The lesion resolved after one month of oral itraconazole treatment. However, the patient had to complete six months of antifungal treatment to prevent recurrence.

Oral Itraconazole in the Treatment of Chronic Rhinosinusitis

RATIONALE: We conducted a retrospective cohort study to determine the clinical efficacy of oral itraconazole treatment in patients with chronic rhinosinusitis (CRS).METHODS: Patients with physician-diagnosed CRS and sinus CT consistent with CRS and treated with oral itraconazole 200 mg once a day or twice daily from June 2005 to April 2006 were enrolled into the study. Charts were reviewed for symptoms, sinus CT, presence of nasal polyps by endoscopy, blood eosinophilia, and itraconazole treatment efficacy. A univariate logistic regression analysis was employed to determine whether symptoms, presence of nasal polyps, and blood eosinophilia predicted efficacy to itraconazole. P < 0.05 was considered statistically significant.RESULTS: Forty-eight subjects were enrolled (mean age of 52 ± 12 years; 25 males and 23 females) among whom 31(65%) had nasal polyps. The most common symptoms were nasal obstruction [40(83%)], postnasal drainage [25(52%)], and hypo/anosmia [25(52%)]. The most common treatments before itraconazole were sinus surgery (92%), antibiotics (81%), and intranasal steroid (69%). After itraconazole treatment, 30 (70%) of 43 subjects reported an improvement in their symptoms. Patients with nasal polyps were more likely to improve on itraconazole compared to those without nasal polyps [22/27 (81%) vs. 8/16 (50%) p=0.03, respectively]. Six of 48 patients had sinus CTs before and after treatment, and all 6 showed improvement. Blood eosinophilia was observed in 25% of patients, but it did not affect treatment outcomes.CONCLUSIONS: Oral itraconazole may be an effective treatment for CRS in patients with nasal polyps. A larger placebo-controlled study is needed to confirm these findings. RATIONALE: We conducted a retrospective cohort study to determine the clinical efficacy of oral itraconazole treatment in patients with chronic rhinosinusitis (CRS). METHODS: Patients with physician-diagnosed CRS and sinus CT consistent with CRS and treated with oral itraconazole 200 mg once a day or twice daily from June 2005 to April 2006 were enrolled into the study. Charts were reviewed for symptoms, sinus CT, presence of nasal polyps by endoscopy, blood eosinophilia, and itraconazole treatment efficacy. A univariate logistic regression analysis was employed to determine whether symptoms, presence of nasal polyps, and blood eosinophilia predicted efficacy to itraconazole. P < 0.05 was considered statistically significant. RESULTS: Forty-eight subjects were enrolled (mean age of 52 ± 12 years; 25 males and 23 females) among whom 31(65%) had nasal polyps. The most common symptoms were nasal obstruction [40(83%)], postnasal drainage [25(52%)], and hypo/anosmia [25(52%)]. The most common treatments before itraconazole were sinus surgery (92%), antibiotics (81%), and intranasal steroid (69%). After itraconazole treatment, 30 (70%) of 43 subjects reported an improvement in their symptoms. Patients with nasal polyps were more likely to improve on itraconazole compared to those without nasal polyps [22/27 (81%) vs. 8/16 (50%) p=0.03, respectively]. Six of 48 patients had sinus CTs before and after treatment, and all 6 showed improvement. Blood eosinophilia was observed in 25% of patients, but it did not affect treatment outcomes. CONCLUSIONS: Oral itraconazole may be an effective treatment for CRS in patients with nasal polyps. A larger placebo-controlled study is needed to confirm these findings.

Cerebral phaeohyphomycosis masquerading as a parafalcian mass: case report

Background Cerebral phaeohyphomycosis caused by Fonsecaea pedrosoi is a rarity. However, about four cases have been reported in the literature. The disease remains mostly fatal despite employment of new treatment modalities. Case An 18-year-old boy presented seizures of recent onset. Two years back, he developed cutaneous phaeohyphomycosis after a splinter scratch on his chest wall. Imaging revealed a contrast enhancing parafalcian solid mass. Right frontal parasagittal craniotomy was performed and the lesion resected as much as possible, followed by IV amphotericin B and oral itraconazole treatment. The patient has been doing well during a 15-month follow-up period. Discussion Cerebral phaeohyphomycosis is an extremely rare lesion, which could masquerade as a parafalcian mass. Radical surgical removal together with antimicrobials remains the cornerstone treatment of cerebral phaeohyphomycosis.

Framing the Future of Antifungals in Atopic Dermatitis

Atopic dermatitis (AD) is a frequent chronic inflammatory skin disease. Some fungal colonization or infection of the skin may exacerbate AD severity, particularly the so-called head and neck variant. In addition, excessive intestinal colonization by Candida albicans may represent an additional triggering factor. Hence, there is a rationale to use antifungals in selected AD patients. Early trials with topical ketoconazole in head and neck AD showed a decrease in Malassezia colonization, but no significant improvement was observed in the clinical severity. In contrast, clinical improvement and decreased serum IgE were obtained in patients with positive Malassezia radioallergosorbent tests (RASTs) who were treated by oral ketoconazole. Some preliminary data suggested that oral itraconazole treatment in AD patients reduced the need for topical corticosteroids, provided clinical improvement particularly in head and neck AD, reduced the cutaneous and intestinal fungal colonization that may trigger AD, reduced the percentage of positive Malassezia cultures and demonstrated a decrease in C. albicans and Malassezia RAST values. Furthermore, beside its antifungal action, itraconazole in part relieves pruritus and inflammation. In conclusion, oral itraconazole treatment can alleviate AD severity in selected patients. Fluconazole is also effective. Further research is warranted to identify whether the load in skin surface fungal agents, the fungal RAST values and specific prick testing should be assessed in order to optimize the antifungal management in AD patients.

Ostéoarthrite à Pseudallescheria boydii chez un patient porteur de leucémie aiguë lymphoblastique : à propos d'un cas

Pseudallescheria boydii arthritis in a patient with acute lymphoblastic leukemia: a case report. Introduction. — The outcome of neutropenic patients with Pseudallescheria boydii infection is poor. Exegesis. — We report the first case of Pseudallescheria boydii hip arthritis in a patient treated for acute lymphoblastic leukemia. In vitro susceptibility testing showed that the strain was resistant to amphotericin B, fluorocytosine and nystatin, but susceptible to itraconazole. The patient received oral itraconazole (600 mg/day) and clinical symptoms initially resolved. Two months later, after a course of chemotherapy and high-dose steroids while receiving oral itraconazole treatment, the patient developed fever, skin lesions and disseminated lung infiltrates due to Pseudallescheria boydii and finally died. Conclusion. — This case illustrates the severity of fungal infections due to Pseudallescheria boydii despite a presumably well-conducted antifungal therapy.

Folliculitis in Down's syndrome

Twenty-two male and 20 female adults with Down's syndrome were examined. Ten of the men and two of the women had a follicular rash consistent with Malassezia folliculitis. Oral itraconazole treatment produced a significant improvement in the rash, accompanied by a decrease in the skin Malassezia count. Clinical relapse occurred when therapy was discontinued, and was accompanied by return of the Malassezia yeasts.