G. Cauwenbergh

Posttreatment itraconazole levels in the nail: New implications for treatment in onychomycosis

BACKGROUND A problem in the treatment of onychomycosis is the lengthy duration of therapy. The pharmacokinetics of itraconazole suggest a potential for briefer treatment. OBJECTIVE This study was designed to investigate itraconazole nail kinetics in 39 patients with onychomycosis in relation to their therapeutic outcome. METHODS All patients received itraconazole for 3 months at a dose of 100 or 200 mg daily. Itraconazole levels of distal nail clippings were determined during a 6-month posttherapy period. RESULTS Therapeutic itraconazole concentrations were found in the nail plates of fingernails and toenails for up to 6 months after treatment. Cure of the toenails was observed in 79% of the patients treated with the 200 mg dosage and in 26% of those treated with 100 mg at 6 months after therapy. CONCLUSION The data suggest that the drug reaches the nail via incorporation into the matrix and by diffusion from the nail bed and is eliminated with regrowth of the nail after discontinuation of treatment.

Treatment of dandruff with a 2 % ketoconazole scalp gel: a double-blind placebo-controlled study

F patients (33 men, 10 women) with.a median age of 33 years (range 15-59) received double-blind medication consisting of bottles containing 100 ml of a 2% ketoconazole scalp gel or an identical placebo jgel on a computer-randomized basis. At entry into the study, the patients had had dandruff for periods ranging from 1 month to 25 years (median 4 years). Overall, the ketoconazole and placebo groups were not statistically different for sex, age, duration of dandruff, and previous therapy. Patients were instructed to wash their hair twice weekly for 4 consecutive weeks. The washing procedure had to be performed with plenty of warm water. The scalp gel was distributed over the scalp area by gently massaging and was left on the scalp for 3-5 minutes. Afterward, the hair was rinsed with plenty of warm water, and hair was dried with a warm air current. At the end of the 4-week treatment period, a final assessment of the objective symptom (desquamation) and subjective symptom (pruritus) was given. Also, the onset of improvement was recorded.

Progress in antifungal chemotherapy

SummaryThe field of antifungal chemotherapy is undergoing rapid change at present, with an accelerating pace of introduction of new agents. The problems at present include the need for more effective agents, particularly with novel modes of action. Fungal infection must be considered more frequently in differential diagnosis, and methods developed for early diagnosis. The literature must be improved, with more precise terms. Trials comparing agents are needed, as are studies directed at determining the appropriate length of therapy.In vitro susceptibility testing must be standardized, and clinical correlations examined. Particular problem areas in current therapy are deep candida infections, zygomycotic infections, fungal endocarditis and meningitis, cryptococcosis in AIDS patients, and ocular infections withFusarium species. Immunomodulating or “pro-host” drugs present an as yet unexplored avenue for clinical therapy. Regimes to prevent fungal infection need improvement. Until the needed advances occur, we must be resourceful in minimizing the toxicity of the agents presently available.ZusammenfassungAuf dem Gebiet der antimykotischen Chemotherapie vollzieht sich zur Zeit ein rascher Wandel. In immer kürzeren Abständen werden neue Substanzen eingeführt. Doch werden weiterhin wirksamere Medikamente mit neuem Wirkungsmechanismus benötigt. Pilzinfektionen sollten in der Differentialdiagnose häufiger bedacht und Methoden für eine Frühdiagnostik entwickelt werden. Publikationen sind im Hinblick auf eine präzisere Terminologie verbesserungsbedürftig. Vergleichende Therapiestudien und Studien, die die erforderliche Therapiedauer bestimmen, sollten durchgeführt werden. Es ist erforderlich, dieIn vitro-Empfindlichkeitstestung zu standardisieren und die Ergebnisse zur klinischen Wirksamkeit eines Antimykotikums in Beziehung zu setzen. Besondere Probleme stellt derzeit die Behandlung tiefer Candida-Infektionen, von Infektionen durch Zygomyceten, der Pilz-Endokarditis und -Meningitis, der Kryptokokkose bei AIDS-Patienten und von Augeninfektionen durchFusarium Spezies dar. Unerforscht sind noch die Möglichkeiten immunmodulierender, die körpereigene Abwehr stärkender Medikamente für die Klinik. Die Therapieschemata zur Verhütung von Pilzinfektionen sind verbesserungsbedürftig. Bis die nötigen Fortschritte erreicht sind, müssen wir mit den derzeit verfügbaren Medikamenten sorgfältig umgehen, um ihre Toxizität möglichst gering zu halten.The field of antifungal chemotherapy is undergoing rapid change at present, with an accelerating pace of introduction of new agents. The problems at present include the need for more effective agents, particularly with novel modes of action. Fungal infection must be considered more frequently in differential diagnosis, and methods developed for early diagnosis. The literature must be improved, with more precise terms. Trials comparing agents are needed, as are studies directed at determining the appropriate length of therapy.In vitro susceptibility testing must be standardized, and clinical correlations examined. Particular problem areas in current therapy are deep candida infections, zygomycotic infections, fungal endocarditis and meningitis, cryptococcosis in AIDS patients, and ocular infections withFusarium species. Immunomodulating or “pro-host” drugs present an as yet unexplored avenue for clinical therapy. Regimes to prevent fungal infection need improvement. Until the needed advances occur, we must be resourceful in minimizing the toxicity of the agents presently available. Auf dem Gebiet der antimykotischen Chemotherapie vollzieht sich zur Zeit ein rascher Wandel. In immer kürzeren Abständen werden neue Substanzen eingeführt. Doch werden weiterhin wirksamere Medikamente mit neuem Wirkungsmechanismus benötigt. Pilzinfektionen sollten in der Differentialdiagnose häufiger bedacht und Methoden für eine Frühdiagnostik entwickelt werden. Publikationen sind im Hinblick auf eine präzisere Terminologie verbesserungsbedürftig. Vergleichende Therapiestudien und Studien, die die erforderliche Therapiedauer bestimmen, sollten durchgeführt werden. Es ist erforderlich, dieIn vitro-Empfindlichkeitstestung zu standardisieren und die Ergebnisse zur klinischen Wirksamkeit eines Antimykotikums in Beziehung zu setzen. Besondere Probleme stellt derzeit die Behandlung tiefer Candida-Infektionen, von Infektionen durch Zygomyceten, der Pilz-Endokarditis und -Meningitis, der Kryptokokkose bei AIDS-Patienten und von Augeninfektionen durchFusarium Spezies dar. Unerforscht sind noch die Möglichkeiten immunmodulierender, die körpereigene Abwehr stärkender Medikamente für die Klinik. Die Therapieschemata zur Verhütung von Pilzinfektionen sind verbesserungsbedürftig. Bis die nötigen Fortschritte erreicht sind, müssen wir mit den derzeit verfügbaren Medikamenten sorgfältig umgehen, um ihre Toxizität möglichst gering zu halten.

Fungal cultures on cyanoacrylate skin surface strippings as a dose-finding method for topical antifungals. A placebo-controlled study with 0·25% and 0·50% itraconazole cream

The antimycotic activities of 0.25% and 0.50% itraconazole cream were compared in the stratum corneum after once-daily applications for 1 week. Two groups of 12 healthy volunteers applied either itraconazole or placebo on the inner side of each forearm, in a double-blind design. Cyanoacrylate skin surface strippings (CSSS) were taken on days 8, 11 and 21. Conidia or yeasts of selected fungi (Trichophyton rubrum, Trichophyton metagrophytes, Microsporum canis and Candida albicans) were deposited on CSSS. Fungal growth on CSSS was assessed in time by computerized image analysis to derive the inhibitory effect of the previously applied antifungal preparations. Comparable antimycotic activity was found against dermatophytes for both concentrations. Itraconazole 0.50% appeared to be more active than 0.25% against C. albicans. The 0.50% concentration yielded prominent fungitoxic effect after 1 week of treatment, and showed a lingering effect in the stratum corneum for at least 3 days. This method could be useful in a pre-clinical setting and serve as a predictive tool for further clinical dose-finding studies with topical antimycotics.