Systemic Ketoconazole Research Articles

A Comparative Study of Efficacy, Safety and Relapse Rate of Three Drugs; Systemic Ketoconazole, Systemic Itraconazole and Topical Oxiconazole in the Treatment of Pityriasis Versicolor

Aim : The aim of our study was to evaluate the efficacy, safety and relapse rate of systemic Ketoconazole, systemic Itraconazole and topical Oxiconazole in the treatment of pityriasis versicolor. Study design : 94 patients who had pityriasis versicolor were included in the study. The patients were given Ketoconazole, Itraconazole and Oxiconazole randomly and were followed up at the interval of 15 days, 1 month and 3 months for assessement of clinical and mycological cure. Results : In assessment of clinical parameters maximum improvement in scaling, pigmentation and pruritus was seen in Oxiconazole group compared to itraconazole and ketoconazole group. During the study it was observed that rate of clinical cure was maximum in Oxiconazole group (76.67%) as compared to Itraconazole (58.82%) and Ketoconazole group (46.66%). Mycological cure during visit 2 in Oxiconazole group was (83.33%), as compared to (88.2%) Itraconazole group and (88.7%) Ketoconazole group. During visit 3, mycological cure was present in 93.3% cases in Oxiconazole group, 94.1% in Itraconazole group and 93.3% in Ketoconazole group. During visit 4 mycological cure was assessed which showed 88.7% cure rate in Oxiconazole group compared to 88.2% in Itraconazole group and 88.7% in Ketoconazole group. These results suggested presence of relapse in 6.6% cases in both Oxiconazole and Ketoconazole group and 5.9% cases in Itraconazole group. There were no side effects with oxiconazole group while cases treated with ketoconazole and itraconazole had side effects like nausea and urticaria. Conclusion : According to the present study we conclude that topical Oxiconazole therapy was more effective as compared to systemic Itraconazole and Ketoconazole therapy in early improvement of scaling, pigmentation and pruritus secondary to Pityriasis versicolor with no significant side effects.

A Comparative Study of Efficacy, Safety and Relapse Rate of Three Drugs; Systemic Ketoconazole, Systemic Itraconazole and Topical Oxiconazole in the Treatment of Pityriasis Versicolor

<strong>Aim</strong>: The aim of our study was to evaluate the efficacy, safety and relapse rate of systemic Ketoconazole, systemic Itraconazole and topical Oxiconazole in the treatment of pityriasis versicolor. <strong>Study design</strong>: 94 patients who had pityriasis versicolor were included in the study. The patients were given Ketoconazole, Itraconazole and Oxiconazole randomly and were followed up at the interval of 15 days, 1 month and 3 months for assessement of clinical and mycological cure. <strong>Results</strong>: In assessment of clinical parameters maximum improvement in scaling, pigmentation and pruritus was seen in Oxiconazole group compared to itraconazole and ketoconazole group. During the study it was observed that rate of clinical cure was maximum in Oxiconazole group (76.67%) as compared to Itraconazole (58.82%) and Ketoconazole group (46.66%). Mycological cure during visit 2 in Oxiconazole group was (83.33%), as compared to (88.2%) Itraconazole group and (88.7%) Ketoconazole group. During visit 3, mycological cure was present in 93.3% cases in Oxiconazole group, 94.1% in Itraconazole group and 93.3% in Ketoconazole group. During visit 4 mycological cure was assessed which showed 88.7% cure rate in Oxiconazole group compared to 88.2% in Itraconazole group and 88.7% in Ketoconazole group. These results suggested presence of relapse in 6.6% cases in both Oxiconazole and Ketoconazole group and 5.9% cases in Itraconazole group. There were no side effects with oxiconazole group while cases treated with ketoconazole and itraconazole had side effects like nausea and urticaria. <strong>Conclusion</strong>: According to the present study we conclude that topical Oxiconazole therapy was more effective as compared to systemic Itraconazole and Ketoconazole therapy in early improvement of scaling, pigmentation and pruritus secondary to Pityriasis versicolor with no significant side effects.

Superficial Fungal Infections

Superficial Fungal Infections

In vitro antifungal susceptibility of Malassezia pachydermatis from dogs with and without skin lesions

Canine Malassezia dermatitis is frequently treated with systemic ketoconazole (KTZ) and itraconazole (ITZ). However, no information is available on the antifungal susceptibility to azoles and allilamine of Malassezia pachydermatis isolates from dogs with or without skin lesions. The present study was designed to evaluate the in vitro antifungal susceptibility of M. pachydermatis strains from dogs with or without skin lesions to KTZ, ITZ, miconazole (MICO), fluconazole (FLZ), posaconazole (POS), voriconazole (VOR) and terbinafine (TER) using the Clinical and Laboratory Standards Institute reference Broth Microdilution Method (CLSI M27-A2). The association between the susceptibility to antifungal compounds and the origin of M. pachydermatis, from skin with or without lesions has been also assessed. A total of 62 M. pachydermatis strains from healthy dogs (i.e., Group A=30) or with skin lesions (i.e., Group B=32) were tested. ITZ, KTZ and POS showed the highest activity against M. pachydermatis strains, whereas MICO TER and FLZ the lowest. A higher number of Malassezia resistant strains were registered among isolates from Group B than those from Group A.This study indicates that M. pachydermatis strains were susceptible to ITZ, KTZ, and POS. However, dogs with lesions may harbour strains with low susceptibility to antifungal agents and displaying cross-resistance phenomena to azole. The antifungal therapy in Malassezia infections requires careful appraisal of choice of drugs especially in cases of unresponsiveness to antifungal treatment or recurrent infections.

Mixed fungal keratitis of Penicillium species and Acremonium species

Mixed fungal keratitis of two different genera has rarely been reported. We described a case of mixed fungal keratitis of Penicillium sp and Acremonium sp. A 67-year-old male developed severe keratitis after undergoing superficial corneal trauma of his right eye while picking herbs ( Ficus erecta Thunb. var.) 3 days earlier. Corneal stromal infiltration with a feathery border and a surrounding immunological reaction ring was noted without epithelial defect. Direct smear examination of corneal scraping showed the presence of filamentous fungi, and topical natamycin (5%) hourly was prescribed along with systemic voriconazole. However, hypopyon soon developed. Culture revealed growths of Penicillium sp and Acremonium sp. Combined treatment with topical amphotericin B (0.1%) and natamycin, alternated hourly, and systemic ketoconazole resulted in resolution in a fluctuating course. The culture results were important for the diagnosis of a mixed infection and together with careful follow-up were critical for a good result.

An azole-resistant isolate of Malassezia pachydermatis

Canine Malassezia dermatitis (MD) is frequently treated with systemic ketoconazole (KTZ) and itaconazole (ITZ). However, the antifungal susceptibility of clinical isolates of M. pachydermatis from dogs and cats to the azoles has not been well investigated. In the present study, the in vitro susceptibility of the standard strain (CBS1879: the neotype strain of M. pachydermatis) and 29 clinical isolates of M. pachydermatis to the azoles was measured by a modified CLSI M27-A2 test using modified Dixon medium as well as by the E-test. The minimum inhibitory concentrations (MICs) of the 30 isolates of M. pachydermatis (including the neotype strain) against KTZ and ITZ were <0.03μg/ml by the two methods. The MICs of 1 clinical isolate (ASC-11) were 1 and 2μg/ml against KTZ, and 2 and 8μg/ml against ITZ, by the modified CLSI M27-A2 test and the E-test, respectively. Thus, isolate ASC-11 may be resistant to these azoles, making this the first report of a resistant isolate of M. pachydermatis to KTZ and ITZ.

Ketoconazole in the treatment of central serous chorioretinopathy: a pilot study

The aim of this study was to evaluate a possible effect of systemic ketoconazole on visual acuity (VA) and retinal thickness in patients with acute central serous chorioretinopathy (CSCR). Fifteen consecutive patients were treated with ketoconazole 200 mg/day for a period of 4 weeks. Another 15 patients served as a control group. Baseline examination and review after 4 weeks included VA testing and measurement of neuroretinal or pigment epithelial detachment by optical coherence tomography (OCT). Fluorescein angiography was performed to verify the diagnosis. At baseline, mean VA in Snellen units was 0.6+/-0.2 (logMAR 0.2+/-0.7) in the treatment group and 0.7+/-0.3 (logMAR 0.2+/-0.5) in the control group. On OCT, mean neuroretinal or pigment epithelial detachment measured 288+/-163 microm in the ketoconazole group and 225+/-51 microm in the control group, respectively. Four weeks later, mean VA improved in both groups. On OCT, neuroretinal or pigment epithelial detachment decreased in both the treatment and control groups. The differences were not statistically significant. Although a pharmacological decrease in endogenous cortisol synthesis appears to be a rational approach in the treatment of CSCR, systemic ketoconazole at 200 mg/day was not associated with a significantly better outcome in this preliminary study.

A case of cutaneous protothecosis successfully treated with local thermal therapy as an adjunct to itraconazole therapy in an immunocompromised host

We report a case of human protothecosis in an immunocompromised host which was caused by Prototheca wickerhamii and was successfully treated with thermal adjunct therapy combined with systemic itraconazole therapy. A 78-year-old man taking 30 mg prednisolone daily had a 1-week history of erythematous plaques on the dorsal aspect of his right hand and forearm after sustaining a small traumatic injury. Histopathology of the lesions revealed granulomatous inflammatory changes with numerous microorganisms that had multiple septations in their cytoplasm. On the basis of mycological features and the results of the sugar assimilation test, the etiologic agent was identified as Prototheca wickerhamii. Although the lesion showed no response to the systemic itraconazole therapy and topical ketoconazole treatment, a complete resolution was achieved by the use of thermal therapy as an adjunct to systemic itraconazole.

Microsporum canis infection in a red fox (Vulpes vulpes)

Summary A 3-month-old male red fox that was in contact with a Persian cat referred to the small animal hospital, Faculty of Veterinary Medicine, University of Tehran with multi-focal circular non-pruritic skin lesions and hair loss mainly on the head and extremities. A complete series of dermatologic tests such as Wood’s light examination, direct microscopic examination, and fungal culture were performed. The isolated pathogen was identified as Microsporum canis. The animal was treated using topical and systemic ketoconazole for 4 weeks. After treatment, the lesions were completely disappeared, and there was no recurrence of skin lesions during the follow-up period. It should be noted that asymptomatic cats may carry M. canis, thus may increase the risk of fungal infections for their owners and other pets as well. This is the first documented report of M. canis infection and its treatment in a red fox.

Paecilomyces lilacinus olecranon bursitis in an immunocompromised host: case report and review

Paecilomyces lilacinus is a little-known mold that causes rare cases of invasive infections in humans regardless of their immune status. We present a unique case in an immunocompromised host with olecranon bursitis because of multidrug-resistant P. lilacinus treated with systemic ketoconazole therapy and surgical debridement. Recognition of this fungus is difficult initially because of its appearance, which can be confused with that of other fungi. Once this organism has been identified, it is recommended that antifungal susceptibility testing be obtained to guide appropriate therapy. Combination of therapeutic modalities requires case-by-case assessment. Surgical debridement and removal of prosthesis may be indicated. Although P. lilacinus can be a laboratory contaminant, in our case, causation was established as the organism grew in repeated cultures, sufficient to confirm a fungal origin for his bursitis.

Voriconazole for the treatment of refractory Aspergillus fumigatus keratitis

We report a case of Aspergillus fumigatus keratitis in a 53-year-old, well-controlled diabetic female who did not respond to standard antifungal treatment. She was started on topical natamycin eye drops, but the infiltrate continued to progress. Topical amphotericin B and systemic ketoconazole was added, however, there was no response and the infiltrate increased further. She was then switched to topical and systemic voriconazole. Steady resolution of the infiltrate was noted within 2 weeks of therapy.

Corneal ulcer due toNeocosmospora vasinfectain an immunocompetent patient

We report a case of Neocosmospora vasinfecta keratitis in a 55-year-old man. While the patient did not recall any specific trauma or eye injury, he might have sustained a trivial wound during the course of his duties as a farmer. Direct examination of corneal scrapings revealed fungus filaments. As topical treatment with natamycin and econazole and subsequent systemic ketoconazole therapy failed, a full thickness therapeutic keratoplasty was performed. Post-operative treatment with amphotericin B and clotrimazole combined with cyclosporine resulted in a complete cure. The residual corneal infiltration in the recipient cornea became clear in a week. The fungal isolate was initially identified as a Fusarium species, but later reidentified through the use of morphological characteristics and sequence analysis of the internal transcribed spacer region as N. vasinfecta. The latters is a Hypocrealean fungus not hitherto reported as a causative agent of keratomycosis.

Case of Keratitis Caused by Aspergillus tamarii

We report a case of Aspergillus tamarii keratitis. Ocular injury was known to be a predisposing factor. Topical natamycin and econazole treatment and subsequent systemic ketoconazole treatment proved effective. The isolate was identified by morphological characteristics and sequence analysis as A. tamarii, a member of Aspergillus section Flavi not hitherto reported from keratomycosis.

Systemic Antifungal Therapy for Cutaneous Infections in Children

The skin, hair and nails are common sites for superficial dermatophyte infection in children. Systemic antifungal therapy is indicated for a variety of cutaneous disorders in the pediatric population. In this article, we review the common indications for the use of systemic antifungal therapy, including terbinafine, ketoconazole, itraconazole, fluconazole and griseofulvin, in children and young adults. Cutaneous fungal infections that generally require systemic antifungal therapy include tinea capitis and onychomycosis. Tinea capitis, which is most often caused by Trichophyton tonsurans, is among the most common fungal infections in children. Tinea capitis occurs primarily in the prepubertal age group. Immunosuppression, eg, human immunodeficiency virus infection, does not increase the frequency of dermatophyte infection; however, the severity of disease and the likelihood of recurrence are greater in this population. Although griseofulvin remains the recommended therapy, terbinafine, itraconazole and fluconazole have been reported to show efficacy in the treatment of tinea capitis in children. Onychomycosis refers to dermatophyte and nondermatophyte infections of the nail unit. The most common dermatophytes responsible for causing onychomycosis include Trichophyton rubrum and Trichophyton mentagrophytes. Children with onychomycosis should be examined for the presence of tinea capitis or pedis, and parents should also be examined for onychomycosis. Most children with onychomycosis have distal subungual onychomycosis, which requires systemic treatment. For this reason, the diagnosis of onychomycosis should always be confirmed by mycology culture. Effective treatment may require prolonged courses of therapy, and the rate of recurrence is high. Currently in North America, there is no FDA-approved treatment of onychomycosis in children. However, terbinafine, itraconazole, and fluconazole are generally well-tolerated and safe and have few side effects. Laboratory monitoring of liver function in patients treated with these agents is prudent. Griseofulvin, although considered the treatment of choice for dermatophyte infections in children, is not recommended for the treatment of onychomycosis given the long duration of treatment and high recurrence rate. Griseofulvin is available in an oral suspension; however, terbinafine is available only in tablet form. Although itraconazole is also available in an oral solution, this is not approved for onychomycosis and contains cyclodextrin, which may cause diarrhea and has induced pancreatic adenocarcinoma in rats. Fluconazole is also available as an oral suspension, but is not FDA-approved for dermatophyte infections.

Drug-induced delusions of parasitosis during treatment of Parkinson's disease

Drug-induced delusions of parasitosis during treatment of Parkinson's disease

PH-Dependent Dissolution in Vitro and Absorption in Vivo of Weakly Basic Drugs: Development of a Canine Model

The aim of this research was to develop a pH-dependent canine absorption model for studying pH effect on both dissolution in vitro and pharmacokinetics in vivo using the weak bases ketoconazole and dipyridamole as model drugs. Ketoconazole and dipyridamole pH-dependent dissolution profiles in vitro were determined by dissolution test at different pH values using USP apparatus II and an Opt-Diss Fiber Optic UV System. In vivo absorption studies for ketoconazole and dipyridamole were performed with crossover design in three groups of beagle dogs under control (no treatment), pentagastrin, and famotidine treatments. Ketoconazole and dipyridamole plasma concentrations were quantified by gradient high performance liquid chromatography mass spectroscopy (HPLC MS/MS). Pharmacokinetic parameters were determined from individual plasma concentration vs. time profiles. Ketoconazole and dipyridamole displayed pH-dependent dissolution. Increasing the pH of the dissolution medium from 1.2 to 6.8 reduced the extent of dissolution of ketoconazole and dipyridamole at 1 h by 96% and 92%, respectively. In vivo studies in dogs under control (no treatment), pentagastrin, and famotidine treatments show marked differences in systemic ketoconazole and dipyridamole exposure. Area under the concentration-time curve (AUC) increased more than 4-fold as compared to control group, whereas it increased nearly 30-fold for ketoconazole and 9-fold for dipyridamole with pentagastrin (gastric pH approximately 2-3) as compared to famotidine (gastric pH approximately 5-7.5) treatment. This work demonstrates a pH-dependent dissolution in vitro and absorption in vivo for the weak bases ketoconazole and dipyridamole independent of food effects. This model is useful to examine pH-dependent effects on oral drug absorption and for screening formulations to overcome the pH dependency.

Aspergillus flavus keratitis after laser in situ keratomileusis

PURPOSE: To report a case of fungal keratitis caused by Aspergillus flavus after laser in situ keratomileusis surgery. METHODS: Case report. A 24-year-old woman developed pain, redness, decreased vision, and an infiltrate posterior to the corneal flap in her right eye 3 days after laser in situ keratomileusis. On referral, approximately 3 weeks after laser in situ keratomileusis, examination of the right eye revealed light perception vision, a large full-thickness corneal infiltrate, and hypopyon. Corneal scrapings were taken for direct microscopic examination and culture. RESULTS: Corneal scraping revealed the presence of fungal filaments in smears and in culture. The fungus was identified as A. flavus. Intensive topical natamycin and systemic ketoconazole therapy was initiated. Despite intensive medical treatment, the infiltrate progressed and the patient was subjected to a therapeutic penetrating keratoplasty. There was no recurrence of infection after surgery. At last follow-up 4 months after surgery, the eye was quiet with graft edema. CONCLUSION: Fungal keratitis is a rare complication of laser in situ keratomileusis surgery. In a case that does not respond to medical treatment, early surgical intervention must be considered.

Dermatophytosis due to Microsporum persicolor (13 cases) or Microsporum gypseum (20 cases) in dogs.

A retrospective study of 20 cases of dermatophytosis due to Microsporum gypseum and 13 cases due to Microsporum persicolor seen over an 8-year period is reported. These skin diseases are rare (1.3% of our canine case load) and pleomorphic, from localized erythematous and squamous or suppurative lesions (kerions) to extensive or generalized erythematous, alopecic, scaling, crusting and eventually papular and pustular dermatoses. Such dermatophytoses are diagnosed by fungal culture, and in some instances rapidly by dermatohistopathology with periodic acid-Schiff staining (3/3 cases of Microsporum gypseum infection and 5/7 cases of Microsporum persicolor infection). Therapy with topical and/or systemic azole derivatives (topical enilconazole, miconazole, econazole and systemic ketoconazole, respectively) was successful in all cases, with only two relapses, which were easily controlled.

Antifungal activity of ketoconazole and other azoles against Malassezia furfur in vitro and in vivo.

The in vitro activity of several antifungal agents (ketoconazole, miconazole, econazole, fenticonazole, itraconazole, fluconazole) in routine clinical use against Malassezia furfur infections has been studied with freshly isolated strains of M. furfur from pityriasis versicolor lesions. The results indicate that the drugs tested exert a good activity, and both ketoconazole and itraconazole appear very active (0.8 mg/l respectively). Hair samples from the beards of volunteer patients affected by pityriasis versicolor but otherwise healthy were examined to determine ketoconazole levels during oral therapy (one or two 200 mg tablets daily). It was shown that the drug progressively accumulates in the beard, reaching levels proportional to the dose administered, although blood levels did not increase in parallel. The study of drug concentration profile has evidenced a long ketoconazole persistence in the beard at therapeutic levels. In conclusion, the possibility of reaching high and lasting ketoconazole levels in the keratin layer of the epidermis indicates that systemic ketoconazole therapy could be useful for eradication of M. furfur in patients affected by pityriasis versicolor.

Pityrosporum (Malassezia) folliculitis in Saudi Arabia-diagnosis and therapeutic trials

Pityrosporum folliculitis (PF) is frequently misdiagnosed as acne vulgaris, resulting in unnecessary and prolonged treatment. Sixty-two patients with PF seen in the Dermatology Clinic, King Gahad Hofuf Hospital, Saudi Arabia were evaluated clinically. The diagnosis was confirmed by routine histology with haemotoxylineosin staining and Periodic acid-Schiff staining. Scrapings of the lesions, especially the molluscum-like papules, were mounted in KOH/Parker blue ink and examined under the microscope. Patients, divided into three groups as follows, were given treatment for 4 weeks: (1) 20 were treated with ketoconazole, 200 mg orally in addition to ketoconazole shampoo 2% daily; (2) 20 were given only ketoconazole, 200 mg daily, orally; (3) 12 used econazole nitrate 1% solution applied twice daily; and (4) 10 used miconazole nitrate 2% cream twice daily. Cases in groups 3 and 4, who did not respond, were given the same treatment as for group 1. All who responded were kept on ketoconazole shampoo 2% twice weekly. PF was commoner in young adult females as the female to male ratio was 2:1 while the mean age was 21.5 years. The most common site involved was the trunk (95%) in the form of papules, pustules and molluscoid lesions. The latter type of lesion yielded the highest number of spores using KOH/Parker blue ink. Biopsy was positive in 87% of the patients but is usually not necessary. Combined topical and systemic ketoconazole produced clearance of the lesions in 20 patients (100%), while systemic therapy only resulted in 75% clearance (15 of 20). Topical econazole and miconazole failed in 20 of 22 (90%) and improved only two patients. There were no significant side-effects from the drugs.