Treatment of tinea imbricata: a randomized clinical trial using griseofulvin, terbinafine, itraconazole and fluconazole.

BACKGROUND: Griseofulvin has been the mainstay of treatment for tinea imbricata (TI) for decades; however, there have been few reports of efficacy of newer antifungals in the treatment of this condition. Many patients with TI have several obstacles to treatment due to their remote geographical locations and the primitive nature of their societies. OBJECTIVES: The aim of this study was to compare the efficacy of itraconazole, terbinafine and fluconazole with that of griseofulvin after 4 weeks of therapy. METHODS: Patients aged 12-76 years with the clinical diagnosis of TI were randomly assigned to one of four treatment groups: griseofulvin 500 mg twice daily for 4 weeks, terbinafine 250 mg daily for 4 weeks, itraconazole 200 mg twice daily for 1 week or fluconazole 200 mg once weekly for 4 weeks. Disease activity was monitored weekly. Laboratory measurements included monitoring complete blood count and liver function enzymes. Fifty-nine patients were included in the efficacy analysis: 13 in the fluconazole group, 15 in the griseofulvin group, 12 in the terbinafine group and 19 in the itraconazole group. RESULTS: Significant remission was achieved in the terbinafine and griseofulvin groups, lasting up to 8 weeks after cessation of therapy. The fluconazole group experienced no significant remission, and remission was of short duration in the itraconazole group. No adverse events were reported, and non-compliance with medications or follow-up was the only reason for removal from the study. CONCLUSIONS: Griseofulvin and terbinafine are effective in the treatment of TI. The decision of whether to treat at all and which medication to choose depends greatly on the extent of involvement, the social situation, and the availability of resources such as laboratory testing and follow-up.

Disseminated osteoarticular sporotrichosis: treatment in a patient with acquired immunodeficiency syndrome.

We report a case of multiple skin lesions, lymphadenopathy, and osteoarticular sporotrichosis in a man infected with human immunodeficiency virus (HIV). He subsequently died of tuberculosis after successful treatment for osteoarticular sporotrichosis with amphotericin B. We describe the unusual histopathology in disseminated sporotrichosis with acquired immunodeficiency syndrome (AIDS) and compare it with that seen in patients without AIDS. Although the optimal treatment of osteoarticular sporotrichosis in patients with AIDS is unknown, use of amphotericin B in our patient appeared successful. Culture and histologic stains of all tissues taken at autopsy were negative for sporotrichosis. Recent studies of similar cases have shown initial treatment with amphotericin B followed by long-term maintenance with itraconazole to be beneficial.

Successful treatment of tinea capitis with 2% ketoconazole shampoo.

BACKGROUND: Oral antifungal drugs are required for effective treatment of tinea capitis. Topical antifungal shampoo's, namely ketoconazole 2% shampoo or products with selenium sulfide or salicylic acid are recommended as adjunctive therapy. Topical antifungal monotherapy has not been successful in the treated of tinea capitis. The purpose of this open study was to evaluate ketoconazole 2% shampoo as a monotherapy for the treatment of tinea capitis. METHOD: A total of 16 black children, aged 3-6, all with proven tinea capitis caused by Trichophyton tonsurans, were treated daily for 8 weeks with 2% ketoconazole shampoo for a total of 56 treatments. Clinical and mycologic examinations were performed every 2 weeks and again at 4 weeks following treatment. The number of colonies were counted on each plate after each visit. Patients with positive cultures after 8 weeks were placed on oral griseofulvin; those with negative cultures were followed monthly by culture for an additional 12 months. RESULTS: Marked clinical improvement occurred in all patients within 2 weeks and absence of pruritus was noted by the patients as early as 2-6 days. After 8 weeks of shampoo, 14 of the 15 (93%) children were clinically healed. Mycologically, the cultures dropped from a confluent growth of T. tonsurans to less than 100 colonies within 2 weeks; fewer than 50 at week 4 and 20 colonies or fewer after week 6. At 8 weeks of treatment the number of colonies remained at 20 or fewer. Six of the 15 children (40%) had negative cultures after 2, 4, and 6 weeks. One child relapsed at the first 4-week follow-up visit. Five of 15 (33%) of the children remained culturally negative for 12 months post-treatment. CONCLUSIONS: Ketoconazole 2% shampoo alone reduces the number of viable arthroconidia in children with tinea capitis thus reducing the transmissibility and contagious nature of the disease. Unexpectedly, complete cure was obtained in 5/15 (33%) of the children. The children remained clinically and mycologically clear as long as one year after treatment.

Scopulariopsis: an invasive nasal infection.

Scopulariopsis, a soil saprophyte, rarely produces disease and has not been reported to cause invasive nasal destruction in a nonimmunocompromised host. We report the first case of Scopulariopsis in the otolaryngology literature. Prompt surgical debridement is required and usually adequate. Disagreement exists on the use of antifungals as an effective treatment. A case of invasive Scopulariopsis involving the nasal septum of a 72-year-old man is detailed, and successful treatment consisted of local debridement without antifungal drugs. His diagnosis, clinical course, and outcome illustrates the expanding differential diagnosis faced by the otolaryngologist in patients with nasal disease.

Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the toenail.

BACKGROUND: Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens of onychomycosis, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of superficial fungal infections. OBJECTIVE: The purpose of this study was to compare the efficacy and safety of three different doses of fluconazole (150, 300, and 450 mg) given orally once weekly to that of placebo in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. METHODS: In this multicenter, double-blind study, 362 patients with mycologically confirmed onychomycosis were randomized to treatment with fluconazole, 150, 300, or 450 mg once weekly, or placebo once weekly for a maximum of 12 months. To enter the study, patients were required to have at least 25% involvement of the target nail with at least 2 mm of healthy nail from the nail fold to the proximal onychomycotic border. Patients who were clinically cured or improved at the end of treatment were further evaluated over a 6 month follow-up period. At both the end of therapy and the end of follow-up, clinical success of the target nail was defined as reduction of the affected area to less than 25% or cure. RESULTS: At the end of therapy, 86% to 89% of patients in the fluconazole treatment groups were judged clinical successes as defined above compared with 8% of placebo-treated patients. Clinical cure (completely healthy nail) was achieved in 28% to 36% of fluconazole-treated patients compared with 3% of placebo-treated patients. Fluconazole demonstrated mycologic eradication rates of 47% to 62% at the end of therapy compared with 14% for placebo. The rates at the end of follow-up were very similar, indicating that eradication of the dermatophyte was maintained over the 6-month period. All efficacy measures for the fluconazole groups were significantly superior to placebo (p=0.0001); there were no significant differences between the fluconazole groups on these efficacy measures. The clinical relapse rate among cured patients over 6 months of follow-up was low at 4%. Fluconazole was well tolerated at all doses over the 12-month treatment period, with the incidence and severity of adverse events being similar between the fluconazole and placebo treatment groups. Mean time to clinical success in the fluconazole treatment groups was 6 to 7 months. This time frame may be used as a guideline for fluconazole treatment duration. CONCLUSION: The results of this study support the use of fluconazole in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. Doses between 150 to 450 mg weekly for 6 months were clinically and mycologically effective as well as safe and well tolerated.

Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the fingernail.

BACKGROUND: Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of fungal infections. OBJECTIVE: The purpose of this study was to assess the safety and efficacy of oral fluconazole 150, 300, and 450 mg administered once weekly compared with placebo in the treatment of distal subungual onychomycosis of the fingernail caused by dermatophytes. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study enrolling 349 patients with onychomycosis of the fingernails. Clinical and mycologic efficacy as well as measures of safety were assessed monthly for a maximum of 9 months of treatment, with additional safety visits occurring at weeks 2 and 6. For inclusion, patients were required to have clinically and mycologically documented onychomycosis of the fingernail caused by dermatophytes with at least 25% involvement of the target fingernail. After end of therapy, patients with improved or cured fingernails entered a blinded 6-month follow-up without drug treatment during which efficacy was assessed every 2 months. Efficacy was assessed by clinical (visual) and mycologic (microscopic and culture) measures. Clinical measures included assessments of the percentage of target nail involvement, measurement of the distance from the nail fold to the proximal onychomycotic border, and signs and symptoms of onychomycosis. RESULTS: Fluconazole was significantly superior to placebo in eradicating clinical and mycologic symptoms of onychomycosis, both at the end of active treatment and at 6 months after treatment (p=0.0001 for all efficacy measures). At the end of therapy, 91% to 100% of patients in the fluconazole groups were judged clinical successes, defined as reduction of the affected area of the target nail to less than 25% or cure, compared with 8% for placebo. Clinical cure rates at end of therapy were 76%, 85%, and 90% for fluconazole 150, 300, and 450 mg, respectively, compared with 3% for placebo. These clinical success and cure rates were largely maintained or improved during follow-up. Clinical relapse in cured patients during the follow-up period was very low (1.5% to 3.3%). Fluconazole demonstrated mycologic eradication rates of 89% to 100% at the end of treatment and 90% to 99% at the end of follow-up; for placebo the rates were 8% and 12%, respectively. CONCLUSION: Fluconazole administered once weekly is safe and effective in eradicating distal subungual onychomycosis of the fingernail caused by dermatophytes.

Pharmacokinetics of three doses of once-weekly fluconazole (150, 300, and 450 mg) in distal subungual onychomycosis of the toenail.

BACKGROUND: Preliminary clinical data suggest that fluconazole is effective in the treatment of patients with onychomycosis. To design optimum dosage regimens, a better understanding of fluconazole's distribution into and elimination from nails is needed. OBJECTIVE: The purpose of this study was to determine plasma and toenail concentrations of fluconazole. METHODS: In this multicenter, randomized, double-blind investigation, fluconazole (150 mg, 300 mg, or 450 mg) or matching placebo was administered once a week for a maximum of 12 months to patients with onychomycosis of the toenail. A total of 151 subjects participated in the pharmacokinetic assessment. Blood samples and distal toenail clippings from both affected and healthy nails were obtained for fluconazole concentration determinations at baseline, at the 2-week visit, at each monthly visit until the end of treatment, and then at 2, 4, and 6 months (nail samples only at the latter two) after fluconazole was discontinued. RESULTS: Fluconazole was detected in healthy and affected nails at the 2-week assessment in nearly all subjects. The median time to reach steady-state fluconazole concentrations in healthy nails was 4 to 5 months in the three fluconazole dose groups. In affected nails, steady-state fluconazole concentrations were achieved more slowly, with a median time of 6 to 7 months. At the 8-month assessment, affected toenail fluconazole concentrations were higher than corresponding plasma fluconazole concentrations, with ratios of 1.31 to 1.50 in the three active treatment groups. Toenail concentrations of fluconazole declined slowly after treatment was discontinued, with elimination half-lives of 2.5, 2.4, and 3.7 months for the 150, 300, and 450 mg doses, respectively. Measurable fluconazole concentrations were still present in toenails at 6 months after treatment in most subjects. CONCLUSION: Fluconazole penetrates healthy and diseased nails rapidly, yielding detectable concentrations after two weekly doses. Once it penetrates nail, fluconazole persists for up to 6 months or longer after therapy is stopped. These favorable pharmacokinetic characteristics support a once-weekly fluconazole dosage regimen for the treatment of patients with onychomycosis.

A randomized trial to assess once-daily topical treatment of tinea corporis with butenafine, a new antifungal agent.

BACKGROUND: Tinea corporis treatment usually requires topical application of an antifungal agent for 2 to 3 weeks. OBJECTIVE: We evaluated short-term treatment of tinea corporis with butenafine hydrochloride, a new benzylamine with in vitro fungicidal activity. METHODS: Patients (n = 78) were randomly selected to apply butenafine or its cream vehicle alone once daily for 14 days and were periodically assessed until day 42. RESULTS: Butenafine recipients had significantly higher rates of mycologic cure beginning at day 7 (64% vs 9%) with continued improvements through day 42 (88% vs 17%). They also had higher rates of effective treatment (mycologic cure and 90% to 100% symptom improvement) at day 7 (33% vs 0%) with increasing rates through day 42 (81% vs 14%). CONCLUSION: Butenafine provides rapid and persistent antifungal activity and symptom relief in patients with tinea corporis. Significant effects were observed within 7 days of therapy initiation, and increasing effectiveness was observed 4 weeks after therapy.

Aspergillus flavus mycetoma and epidural abscess successfully treated with itraconazole.

Aspergillus spp. rarely cause mycetomata. We report a patient with diabetes and nephrotic syndrome with Aspergillus flavus mycetoma of the back, with the development of an epidural abscess, diskitis and vertebral osteomyelitis. The patient was successfully treated with decompressive laminectomy and a 14-month itraconazole regimen. Serial serum itraconazole levels and quantitative Aspergillus antigen levels were performed. This is the second reported and first extrapedal case of mycetoma caused by A. flavus.

Promoting hospital discharge of infants in safety seats.

In 1990, the American Academy of Pediatrics (AAP) Committee on Injury and Poison Prevention issued a policy statement, "Safe Transportation of Newborns Discharged from the Hospital," recommending that hospitals adopt comprehensive policies, procedures and education programs for the discharge of newborns in child safety seats (CSSs). The purpose of this project was to determine if a statewide educational intervention based on the AAP statement would be effective in bringing about those recommendations in Nebraska hospitals. All hospitals providing newborn services in Nebraska were surveyed prior to and after the intervention to determine the nature and extent of their CSS discharge policies, patient education programs and loan programs. Post-intervention data indicate significant increases in the percentage of hospitals having formal infant CSS discharge policies (from 25.9% to 88%), providing CSS patient education (from 51% to 95%), and having safety seat loan/give-away programs (from 59% to 76%). It is concluded that a comprehensive, statewide educational program can influence hospitals to promote usage of, access to, and education with infant CSSs.

Clinical manifestations and implications of coinfection with Mycobacterium kansasii and human immunodeficiency virus type 1.

We conducted a retrospective study to further elucidate the clinical presentations and prognosis of disease due to Mycobacterium kansasii in patients infected with human immunodeficiency virus (HIV). Forty-nine HIV-infected patients first had M. kansasii isolated at a mean CD4 cell count of 62/mm3 and at a mean interval of 17 months after the diagnosis of AIDS. Seventeen of the 49 patients had disseminated disease caused by M. kansasii. Twenty-nine patients had a positive acid-fast smear of sputum, and 35 were known to be cigarette smokers. At the time of initial isolation of M. kansasii, 13 patients had other concurrent pulmonary isolates and 15 had another mycobacterial species concurrently isolated (the Mycobacterium avium complex in 13 instances). Patients who received antimycobacterial treatment survived longer than those who did not. Only one of the 49 patients was definitively determined to be colonized with M. kansasii without disease; therefore, it appears that pulmonary isolates of M. kansasii in HIV-infected patients are almost always associated with disease. The increase in rates of M. kansasii disease among HIV-infected patients has paralleled the rise of AIDS in Louisiana. So far, this state has recorded more coinfections with M. kansasii and HIV than any other.

Mycetoma caused by Acremonium falciforme: successful treatment with itraconazole.

Mycetoma has not been previously reported in Korea. A case of mycetoma caused by Acremonium falciforme in a 72-year-old man is described. The patient had a single, large, well-demarcated, erythematous, swollen, black, escharlike lesion and three small satellite lesions on his right temporal area. He was treated with itraconazole, and all lesions healed with residual scars in 70 days.

Review of the morphological variations in cutaneous cryptococcosis with a new case resembling varicella.

A 26-year-old black man with acquired immune deficiency syndrome and disseminated cryptococcosis presented with multiple small white vesiculopustular skin lesions on the face, trunk, and upper extremities mimicking varicella. To our knowledge, this is a novel presentation of cutaneous cryptococcal infection. A review of the morphologic variations seen in cutaneous Cryptococcus infections in patients with and without acquired immune deficiency syndrome is also presented.

Blastomycosis and human immunodeficiency virus: three new cases and review.

Reports of blastomycosis in individuals infected with the human immunodeficiency virus (HIV) are increasing. We report on 3 patients co-infected with blastomycosis and HIV (to add to the previously reported 21), and review important clinical aspects and outcomes in all cases. The percentage of patients co-infected with blastomycosis and HIV who had disseminated blastomycosis (63%) was similar to the blastomycosis patients in the general population (67%); however, as a group the patients with HIV were severely immunosuppressed and fared poorly. Severe immunodeficiency was indicated by CD4 counts < 200/mm3 in 85% of co-infected patients. Central nervous system (CNS) involvement occurred in 46% of this group, approximately 5 to 10 times more frequently than in individuals not infected with HIV previously reported at 5% to 10%. The mortality rate from blastomycosis for patients with both HIV infection and blastomycosis is 54%, about 5 times the mortality rate of blastomycosis patients in the general population, previously reported at < 10%. Disseminated blastomycosis in individuals with HIV may appear as deep cutaneous ulcers, as was the case in two of our patients. Although blastomycosis is not an AIDS-defining infection, it may be reasonable to consider HIV testing and measurement of CD4 counts in patients with blastomycosis. Such testing could help identify individuals who are HIV positive but asymptomatic who have blastomycosis, as well as provide useful information regarding a possible association between CD4 cell deficiency and various clinical manifestations of blastomycosis. Patients with HIV and blastomycosis should be examined carefully for any evidence of CNS involvement. Lifetime therapy with ketoconazole or itraconazole is likely to be of benefit to patients with HIV who have been treated successfully for blastomycosis.