Two Colleagues, Two Perspectives: Report From the Society for Pediatric Dermatology Annual Meeting, Part 2

Lawrence F. Eichenfield, MD

Disclosures

October 10, 2002

In This Article

Update: Fungal Infections

Sheila Fallon-Friedlander, MD,[11] Children's Hospital, San Diego, California, and the University of California, San Diego School of Medicine, provided an update on cutaneous fungal infections. She reported that fungal infections in general are increasing in incidence, in part due to an increasing population of at-risk immunocompromised and premature individuals. Resistant organisms are also starting to play a more important role in the epidemiology of fungal infections.

Fortunately, improved diagnostic assays and methods to assess fungal antimicrobial sensitivities are under development or in use, providing us with better means to quickly identify organisms, speciate them, and test sensitivity to therapy. A number of new broad-spectrum antifungals are also available. Finally, large multicenter, randomized clinical trials are providing us with better information on optimal therapy for a number of pediatric fungal infections, including tinea capitis.

Resistance has long been a factor affecting antibiotic therapy for bacterial infections, and it is now clear that similar mechanisms of resistance may hold for fungal organisms as well. Organisms appear to be more resistant to therapy when they exist in a biofilm. Such structures consist of a growth of organisms existing in an extracellular material that they have elaborated. The extracellular material, or glycocalyx, that these aggregations of cells produce appears to confer some degree of protection to the surrounding fungal organisms. Biofilm growths of yeast on medical devices and catheters have been shown to be more resistant to traditional amphotericin B therapy, but do appear more susceptible to newer amphotericin lipid formulations and new antifungal therapies such as voriconazole and the echinocandins.[12] Several new antifungal formulations are now available. They include the lipidized amphotericin formulations (liposomal AMB, AMB lipid complex) that appear to facilitate passage through polysaccharides. Amphotericin binds to fungal cell membrane sterols and induces increased membrane permeability.

The triazoles, such as amphotericin, affect the fungal cell membrane but do their damage by interfering with the synthesis of ergosterol, a crucial component of the fungal cell membrane. New drugs in this category include voriconazole and ravuconazole. Several studies[13,14] have documented the efficacy of voriconazole in the treatment of aspergillus, a fungus that usually proves quite refractory to treatment.

Yet another category of antifungal therapy is the echinocandins, which interfere with fungal cell wall synthesis by blocking production of 1,3-B-D-glucan. Caspofungin, which is now under investigation, appears to be an extremely useful agent in this class.

Dr. Friedlander also discussed new means of diagnosing fungal disease, including the use of polymerase chain reaction evaluation to identify and speciate fungal infections. New methods that quantitate mRNA are helpful in distinguishing living organisms from non-viable elements that may persist in tissue following treatment.[15]

The epidemiology, pathophysiology, and best treatment options of tinea capitis are evolving, said Dr. Friedlander. She related that the prevalence and etiology of tinea capitis varies widely worldwide, with some countries in East and West Africa reporting prevalence rates in excess of 10%. Contrary to previous beliefs, hair-care practices do not appear to significantly affect the acquisition of tinea capitis.[16] One study[17] suggested that the presence of hair loss in association with occipital adenopathy or scale in children is diagnostic of tinea capitis, and suggested that empiric therapy is appropriate when suspicion is high. Other investigators, however, have found that scalp scale in association with some cervical or occipital adenopathy is fairly common in childhood. Dr. Friedlander reviewed a study, presented as a poster by JV Williams, MD (Children's Hospital of the King's Daughters, Norfolk, Virginia), and colleagues at the 2001 World Congress of Pediatric Dermatology in Cancun, and carried out at Dr. Friedlander's center and in Norfolk, Virginia. The authors believe that while the presence of adenopathy lends support to the possibility of tinea infection, culture documentation is still required. They agree that empiric therapy is appropriate when the index of suspicion is high, pending culture results.

Dr. Friedlander reviewed the results of several studies confirming that the newer antifungal therapies (terbinafine, fluconazole, and itraconazole) are efficacious and safe in the treatment of tinea capitis. Gupta and colleagues[18] found that 2 to 3 weeks of treatment of Trichophyton-induced tinea capitis with any of these agents was as efficacious or more efficacious than 6 weeks of therapy with high-dose (20 mg/kg/d microsize) griseofulvin. Dr. Gupta's study was a prospective trial involving 200 children. A large multicenter trial investigating optimum dosing for terbinafine in the treatment of Trichophyton tinea capitis found effective treatment rates of approximately 70% for 2 to 4 weeks of therapy with this drug.[19] Increased duration of therapy did not appear to significantly affect response rates, and an investigation into dosing response revealed that children who received more than 4.5 mg/kg/d fared better than those who received less. Further data are needed regarding the optimal dosing and duration of therapy for terbinafine, and more multicenter trials that compare the efficacy of short-term therapy of the newer antifungals with high-dose griseofulvin therapy would be welcomed.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....