Raza Aly

Ecology and epidemiology of dermatophyte infections

Our knowledge of ecology and epidemiology of dermatophytes and the factors influencing their transmission has helped us understand better the natural history of dermatophytoses. It seems that the anthropophilic agents of scalp infection are being eradicated in developing nations. The exception is Trichophyton tonsurans-related tinea capitis in North America. Microsporum canis is a prevalent agent of tinea capitis in many regions of the world, and this could be related to close association of humans with their pets. Trichophyton violaceum is endemic in certain parts of Eastern Europe, Africa, Asia, and South America but not in North America. Trichophyton rubrum is the most common cause worldwide of tinea pedis, nail infection, tinea cruris, and tinea corporis. Although the incidence of tinea capitis is declining in developed nations, tinea pedis and onychomycosis are becoming more common. The increased use of athletic shoes both by men and women and communal bathing could be contributing factors. Five or six species account for most dermatophytoses globally.

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 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.

Comparative antibacterial efficacy of a 2-minute surgical scrub with chlorhexidine gluconate, povidone-iodine, and chloroxylenol sponge-brushes.

Chlorhexidine gluconate (Hibiclens), povidone-iodine (E-Z Scrub 201), and chloroxylenol (ParaSoft) sponge-brushes were compared for antibacterial efficacy in 2-minute surgical scrubs. Thirty-nine volunteers completed a 7-day baseline period and a 5-day treatment period. Thirteen participants were assigned to a chlorhexidine group, 12 to a povidone-iodine group, and 14 to a chloroxylenol group. Subjects followed a standardized protocol, performing 11 scrubs during the treatment period. Bacterial counts were taken by the glove-juice procedure immediately after scrubbing and at 3 and 6 hours later on days 1, 2, and 5. The use of chlorhexidine achieved significantly (p less than 0.01) greater adjusted mean log10 bacterial count reductions than did povidone-iodine and chloroxylenol at all sampling times, with greater reductions as the study progressed.

Effects of Breathable Disposable Diapers: Reduced Prevalence of Candida and Common Diaper Dermatitis

Infants wearing breathable disposable diapers experienced significantly less diaper dermatitis (DD) compared to infants wearing standard, nonbreathable disposable diapers in a series of double‐blind clinical trials. Severe DD, including confirmed infection with Candida albicans, was reduced by 38–50% among infants wearing highly breathable (HB) diapers. The prevalence of DD was inversely related to the breathability of the garments. The inhibitory effect of breathable diapers on the survival of Candida was further confirmed in controlled experiments with adult volunteers. A suspension of C. albicans cells was applied to delineated sites on the volar forearm. Each site was then covered by a full‐thickness patch from either an HB or a standard diaper. Survival of Candida colonies was reduced by almost two‐thirds in the breathable diaper‐covered sites compared to the control sites.

Bacterial flora in psoriasis

The aerobic bacterial flora of psoriatic plaques, uninvolved skin and the anterior nares of forty psoriatic patients was studied. The incidence od Staphylococcus aureus was 30% in the anterior nares, 20% on the plaques and 13% on the uninvolved skin. S. aureus counts were 3 x 10(2)/cm2 on the plaques and 1-5 x 10/cm2 on the normal skin. The total bacterial counts were also higher on plaques (7-9 x 10(3)/cm2) than on normal skin (3-0 x 10(3)/cm2). The incidence of lipophilic diphtheroids was significantly lower on the plaques (4%) than the normal skin (30%). Eighty percent of the strains of S. aureus isolated from psoriatic patients were resistant to 10 units of penicillin. Because of increased desquamation, psoriatic skin is a public health hazard.

Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: Results from 2 randomized phase-III studies

BACKGROUND Onychomycosis, a fungal nail infection, can impact quality of life. OBJECTIVE We sought to evaluate the efficacy and safety of tavaborole topical solution, 5% for treatment of toenail onychomycosis. METHODS In 2 phase-III trials, adults with distal subungual onychomycosis affecting 20% to 60% of a target great toenail were randomized 2:1 to tavaborole or vehicle once daily for 48 weeks. The primary end point was complete cure of the target great toenail (completely clear nail with negative mycology) at week 52. Secondary end points included completely or almost clear nail, negative mycology, completely or almost clear nail plus negative mycology, and safety. RESULTS Rates of negative mycology (31.1%-35.9% vs 7.2%-12.2%) and complete cure (6.5% and 9.1% vs 0.5% and 1.5%) significantly favored tavaborole versus vehicle (P ≤ .001). Completely or almost clear nail rates also significantly favored tavaborole versus vehicle (26.1%-27.5% vs 9.3%-14.6%; P < .001). Rates of completely or almost clear nail plus negative mycology (15.3%-17.9% vs 1.5%-3.9%) were significantly greater for tavaborole versus vehicle (P < .001). Application-site reactions with tavaborole included exfoliation (2.7%), erythema (1.6%), and dermatitis (1.3%). LIMITATIONS Duration of follow-up is a limitation. CONCLUSION Tavaborole demonstrates a favorable benefit-risk profile in treatment of toenail onychomycosis.

Topical sphingolipids in antisepsis and antifungal therapy

Sphingosine and sphinganine, free sphingolipids of the stratum corneum, arc, in vitro, strongly inhibitor for both bacteria and fungi. Whether or nor they are suitable, indeed active, in vivo was examined: (i) on human volunteers, first as a preventative antiseptic against subsequently applied Staphylococcus aureus and Candida albicans, and second as a restorative antiseptic against the preciously expanded normal skin flora; and (ii) on guinea‐pigs as therapy for experimental C. albicans and Trichophyton mentagrophytes infections. In the antiseptic studies, which involved 200/μg/cm2 of sphinganine in ethanol (50 μ of a 1.6% solution), up to three‐ reductions in the population of target micro‐organisms were obtained, compared with vehicle and untreated controls (P > (0.001). The daily application of sphingosine as 1.5% ethanol petrolatum ointment was able to diminish inflammation slightly in dermatophy guinea‐pigs (P= 0.02–0.05), although the animals remained culture positive over the 3‐week sampling; period. The Candida infections, treated daily with 1.5% sphinganine in ethanol, showed no improvement in inflammation compared with controls, except for 2 days of the 2‐week observation period (P= (0.01‐0.03); however, by the fourth day of therapy the yeast was eliminated in 75% of animals. No gross toxicity was observed among animals or human volunteers. These experiments further support simple sphingolipids as important antimicrobial agents of the cutaneous barrier and point toward a new biochemical approach in treating infectious disease.

A double-blind, randomized comparison of itraconazole capsules and placebo in the treatment of onychomycosis of the toenail

Onychomycosis accounts for up to 50% of all nail infections I and can be chronic and resistant to treatment. 2-4 Itraconazole has antifungal activity against a broad range of dermatophyte infections. 5 It has a high affinity for keratin and penetrates the nail plate by diffusion through the nail bed. It appears in the distal nail within 7 days of initiating therapy and persists in the nail at inhibitory levels for an extended period, 69 up to 9 months in one study. 6 In our study, 75 patients with cfinically and mycologically diagnosed onychomycosis of the toenail were enrolled for treatment with itraconazole, 200 mg, or placebo once daily for 12 weeks. Patients were reexamined at weeks 24, 36, and 48.

The prevalence of dermatophyte infection in patients infected with human immunodeficiency virus.

Background  It is not known whether human immunodeficiency virus (HIV) infection is associated with an increased susceptibility to dermatophytes.

BACTERIAL INTERFERENCE BETWEEN STRAINS OF S. aureus

The ability of one strain of S. aureus to interfere with the growth of a second strain of S. aureus has been observed in vitro and in vivo, in animals and man. The phenomenon termed bacterial interference can be demonstrated in the test tube,1*2 the yolk sac of fertile hens burned surfaces of rabbits and guinea pigs,g the nasal mucosa of guinea pigs,l0 and most recently on the nasal mucosa and intestinal tract of We have been interested in the phenomenon of bacterial interference in man for the past 10 years, and have particularly emphasized the use of the concept in clinical situations. In 1961, epidemiologic observations during a nursery outbreak of staphylococcal disease suggested to us that colonization of the nasal mucosa or umbilical stump of an infant by S. aureus prevented subsequent colonization at the same site by a second strain of S . aureus.13 In order to test this hypothesis, further observations by direct inoculation of S. aureus were made on a series of infants, medical students, nurses, and prisoner For inoculation, a coagulase-positive S. aureus strain of low virulence was used, susceptible to penicillin and incapable of being induced to produce 6-lactamase. The organism is lysed by group I11 staphylococcal phages and is referred to as strain 502A. TABLE 1 presents the data on a series of 78 babies, deliberately colonized. A striking relationship was noted between the prior presence of S. aureus and the failure to implant strain 502A. Coagulase-negative staphylococci exerted a much weaker effect while under the conditions of the experiment. No interference could be demonstrated by other organisms that colonized the nasal mucosa.l3