Efficacy Of Itraconazole Research Articles

Efficacy of antifungal therapy in a nonneutropenic murine model of zygomycosis.

Three isolates of zygomycetes belonging to three different genera (Rhizopus microsporus, Absidia corymbifera, and Apophysomyces elegans) were used to produce a disseminated infection in nonimmunocompromised mice. The therapeutic efficacy of amphotericin B, given intraperitoneally at doses ranging from 0.5 to 4.5 mg/kg of body weight/day, oral itraconazole at 100 mg/kg/day, and oral terbinafine at 150 mg/kg/day was evaluated in this model. The markers of antifungal efficacy were the median survival time, the mortality rate, and the percentage of infected organs. Organ culture was performed along with microscopic direct examinations of tissues to assess the presence of an active infection. An acute and lethal infection was obtained in untreated mice challenged with each of the three strains. The data obtained for direct examinations and qualitative cultures indicate that, due to the nonseptate nature of the hyphae, each technique gives different information and should be used together with the others. Against all three strains, amphotericin B yielded a 90 to 100% survival rate. Itraconazole was inactive against R. microsporus but significantly reduced mortality in mice infected with A. corymbifera or A. elegans. Terbinafine had no beneficial effects against R. microsporus and A. corymbifera despite documented absorption of the drug. Overall, only limited correlations were observed between MICs determined in vitro and in vivo efficacy of the drugs. The efficacy of itraconazole in these models of zygomycosis suggests that this drug, as well as the new azole compounds presently under development, warrants close evaluation.

Itraconazole--perspectives for the management of invasive aspergillosis.

Itraconazole has become an important option in the management of invasive aspergillosis. The compound has potent and broad spectrum antifungal activity in vitro against Aspergillus spp. with a species- and strain dependent fungicidal mode of action. In vivo, the antifungal efficacy of itraconazole has been demonstrated in several non-immunocompromised and immunocompromised animal models of disseminated and invasive pulmonary aspergillosis. Itraconazole is available in oral and intravenous formulations, displays non-linear plasma pharmacokinetics, and is usually well tolerated. Non-comparative clinical data of itraconazole for therapy of suspected or proven invasive aspergillosis suggest response rates similar to those of conventional amphotericin B; however, the experience with itraconazole for induction therapy of invasive aspergillosis is limited, particularly in profoundly neutropenic patients. Itraconazole has an important role for consolidation and maintenance therapy of patients with invasive aspergillosis, and novel combination therapies involving itraconazole are currently under intensive preclinical investigation as to their usefulness for primary therapy.

Age as limiting factor of the efficacy of itraconazole for treatment of onychomycosis

A clinical study was carried out involving 24 patients between 18 and 64 years of age with disto-lateral onychomycosis of finger and/or toenail in whom intermittent therapy with itraconazole was orally administered for 4 months. A follow-up period of 9 months was instituted to monitor the efficacy of the treatment. Clinical and mycological outcome at the end of the study was correlated with a checklist that included age and sex of the patient, site of infection and species of the causative agent. Nails that were free of disease in both gross and mycological examinations were achieved in 58% of our patients. Age was shown to be the only parameter, among those taken into consideration, that was correlated with the cure rate. The association was found to be statistically significant.

Prophylactic Use of Itraconazole for the Prevention of Invasive Pulmonary Aspergillosis in High Risk Neutropenic Patients

Invasive pulmonary aspergillosis (IPA) is an increasing cause of morbidity and mortality in patients with hematologic malignancies. A major program of construction work close to our unit prompted us to evaluate the efficacy of itraconazole prophylaxis in preventing IPA in these patients. During September 1994 to December 1995, 77 patients undergoing 96 neutropenic episodes (mean duration, 19.3 days ×9.1) received itraconazole as antifungal prophylaxis. All patients were treated in laminar air flow rooms. Itraconazole was administered at a loading dose of 600mg/d, (day1 to day3) and 400mg/d on the following days, in 87 instances. In the remaining episodes, the daily dose was 200 or 400mg. Oral doses were adjusted to reach a plasma itraconazole level (PIL) above 1000ng/1. In cases of inadequate PIL or poor oral intake, IV AmphoB was started at a 20 mg daily dose. Five cases of IPA (proven n = 2, probable n = 3) were observed. This represents an incidence of 5.2% of the total number of episodes. One out of 67 (2%) treatment episodes with adequate PIL were associated with IPA as compared to 4 of 29 (14%) episodes with inadequate PIL, (p > 0.02). AmphoB was added in 28 cases because of low PIL (n = 25), and/or antibiotic-resistant fever persistent pulmonary infiltrate (n = 8). These results need to be interpreted with caution, because of the absence of randomization or a control group. The efficacy of Itraconazole in neutropenic patients with high risk IPA has to be confirmed on larger and prospective studies.

African histoplasmosis: therapeutic efficacy of itraconazole

A patient with African form of histoplasmosis was treated for 7 years with ketoconazole, with no response; after a 9-month daily treatment with 100 mg of itraconazole the patient was successfully cured. No evidence of relapse was observed during the 3-year follow-up period.

Itraconazole. A reappraisal of its pharmacological properties and therapeutic use in the management of superficial fungal infections.

Itraconazole is an orally administered triazole antifungal agent. Its spectrum of activity includes dermatophyte, dimorphic and dematiaceous fungi, yeasts, and some moulds. In clinical trials, mycological cure was attained in approximately 70 to 80, > or = 70 and > or = 80% of patients with, respectively, fingernail and toenail onychomycosis (200 mg/day for 3 months), dermatophytosis (100 mg/day for 2 to 4 weeks) and vaginal candidiasis (400 mg/day for 1 day or 200 mg/day for 3 days). Approximately 20 to 30% of patients with onychomycosis may relapse after completion of therapy; relapse rate data are limited for the other indications. Recently developed intermittent regimens of itraconazole (400 mg/day for 1 week per month for 3 to 4 months) appear to have similar efficacy to standard regimens in the treatment of onychomycosis. Shorter, higher dosage itraconazole treatment regimens (200 or 400 mg/day for 1 week) are also beneficial in dermatomycoses. Discrepancies and limitations of study design hamper conclusions about efficacy relative to other antifungal drugs. Newer intermittent and short course higher dosage itraconazole regimens have also not been evaluated in comparative studies. Available studies show that the efficacy of itraconazole appears to be greater than that of griseofulvin, but similar to or lower than that of terbinafine in patients with dermatophyte onychomycosis or cutaneous fungal infections. Moreover, the efficacy of itraconazole may be similar to or lower than that of fluconazole in the treatment of cutaneous mycoses. Comparative data from patients with acute vaginal candidiasis suggest that itraconazole is at least as effective as intravaginal clotrimazole and oral fluconazole, and superior to intravaginal econazole. These results require confirmation. Prescription-event monitoring data indicate that itraconazole is generally well tolerated. Gastrointestinal disturbances, dizziness and headache occur most commonly; liver toxicity has been rarely described. Its usefulness in some clinical situations may be limited because of its ability to interact with various therapeutic agents. In conclusion, itraconazole along with other established agents should be considered a first-line treatment for patients with extensive or recalcitrant cutaneous fungal infections, mixed dermatophyte and Candida onychomycosis or vaginal candidiasis. It is currently considered a second-line drug for dermatophyte onychomycosis; the use of newer intermittent itraconazole treatment regimens may, however, extend its role in the management of this condition. Although itraconazole offers greater benefit than conventional therapies (griseofulvin and ketoconazole) in terms of efficacy and tolerability, wider clinical experience is required to determine its merits relative to the newer agents, terbinafine and fluconazole.

Italian multicentre study with oral itraconazole in recurrent pityriasis versicolor, Preliminary report

AbstractPityriasis versicolor is a common mycosis, characterized by frequent recurrences. Oral itraconazole is very effective in the treatment of this infection but there are no published studies on its prophylactic use. The purpose of our study was to assess further the efficacy of itraconazole in the treatment of recurrent pityriasis versicolor and to investigate its role in prophylaxis. In this ongoing study, 270 patients with recurrent pityriasis versicolor receive 200 mg itraconazole once daily for seven days. Those who experience clinical and mycological cure, sustained one month after the end of treatment, then enter the prophylactic phase of the study and receive either 200 mg itraconazole or two placebo capsules once a month for five months. Of the 48 patients who so far have received the full seven days' treatment with itraconazole, 31 have completed the first phase of the study. Complete clinical cure was achieved in 30(96%) and residual lesions persisted in one. Mycological cure was achieved in all. No adverse events were reported. Nine patients have now entered the prophylactic phase (five taking itraconazole and four placebo). No symptoms so far have reappeared in any of them. Oral itraconazole is a highly effective and well‐tolerated treatment for recurrent pityriasis versicolor. The role of itraconazole in prophylaxis is still undetermined pending completion of the study.

Efficacy of Itraconazole in a Leukaemic Patient with Disseminated Aspergillosis Refractory to Amphotericin B

Invasive aspergillosis in patients with persistent neutropenia is refractory to treatment. Even if the patient recovers from the fungal infection, with an increase of white blood cell count (WBC), inv

The efficacy of itraconazole against systemic fungal infections in neutropenic patients: A randomised comparative study with amphotericin B

In a randomised clinical trial, we compared the efficacy of the new triazole drug itraconazole (200 mg orally twice daily) with that of amphotericin B (0.6 mg/kg daily or 0.3 mg/kg in combination with flucytosine) in neutropenic (less than 500 x 10(6)/l neutrophils) patients with proven or highly suspected systemic fungal infections. Patients with unexplained fever alone were not included in the study. Of the 40 patients enrolled, 32 patients (16 males, 16 females) were evaluable. Sixteen patients (median age 49 years) were treated with itraconazole for a median period of 20 days and 16 patients (median age 32 years) received amphotericin B for a median period of 13 days. The overall clinical response was 10/16 (63%) for patients treated with itraconazole and 9/16 (56%) for patients treated with amphotericin B (P greater than 0.90). Itraconazole seemed to be more effective against Aspergillus infections, whereas amphotericin B seemed to be more effective against candidal infections, although the differences were not statistically significant.

Itraconazole treatment of coccidioidomycosis

purpose: The purpose of this study was to assess the tolerance and efficacy of itraconazole in the treatment of coccidioidomycosis. patients and methods: Fifty-one patients with nonmeningeal coccidioidomycosis were considered for treatment with itraconazole. Forty-nine patients who met study criteria were treated with itraconazole given orally in doses of 100 to 400 mg/day for periods up to 39 months. Of these patients, 12 had osteoarticular disease, 23 had chronic pulmonary disease, and 14 had skin or soft tissue disease. Clinical response was evaluated using a scoring system accounting for lesion number and size, symptoms, culture, and serologic titer. Remission was defined as reduction of the pretreatment score by 50% or more. results: Patients with osteoarticular, chronic pulmonary, and soft tissue disease improved at similar rates. Because two patients had no scoring assessment for efficacy, they were considered inassessable for efficacy. Forty-seven patients are evaluable. Of these patients, 44 have completed therapy, and three are still receiving itraconazole. Of the 44 patients no longer receiving therapy, 25 (57%) achieved remission. Of the 25 patients achieving remission, four later experienced a relapse. Therapy failed in 19 patients (43%). Of these cases, 16 (36%) were clinical failures and three (7%) developed drug intolerance that precluded continuation of treatment. Evaluation of culture conversions was of limited value in the osteoarticular patients, fewer than half of whom had follow-up biopsies. However, culture conversions were a useful index of response in patients with chronic pulmonary disease. During the course of treatment, serologic titers declined in the two groups with extrapulmonary disease, but not in patients with pulmonary coccidioidomycosis. Possible toxicities were generally mild. conclusion: Itraconazole appears efficacious and very well tolerated in patients with coccidioidomycosis.

Efficacy of Itraconazole in Blastomycosis in a Murine Model and Comparison with Ketoconazole

Mice were infected intranasally with B. dermatitidis yeasts, and after infection treated orally. Itraconazole 50-150 mg/kg/day was protective (prolonged survival) against lethal infection, although the infection was not sterilized. Itraconazole was approximately 3 times as potent as ketoconazole. These results suggest advantages for itraconazole therapy clinically.

Treatment of mycoses with itraconazole.

The efficacy of itraconazole, a new oral triazole, was evaluated at doses of 50-400 mg/day in 64 courses: 39 with coccidioidomycosis, and 25 with other mycoses. Among patients with coccidioidomycosis, 21 had pulmonary disease; 10, bone and joint; 8, lymphatic; 6, skin and soft tissue; 3, meningeal; and 1, urogenital. After a mean of 7.1 months of treatment, 17 of 27 evaluable courses (63%) have shown a full response; 8 (30%), a partial response; and 2 (7%), no response. Response to treatment was higher in patients with a shorter duration of illness and in patients with no previous treatment. After a mean of 12 months of treatment, two of five responders off therapy have relapsed. In patients with other mycoses, diagnoses include aspergillosis in six patients; histoplasmosis and tinea in three each; alternariosis, candidiasis, cryptococcosis, blastomycosis, and chromomycosis in two each; and pseudallescheriosis in one. After a mean of 9.4 months of treatment, 14 of 23 evaluable patients (61%) have shown a full response; 2 (8%), a partial response; and 7 (30%), no response. All patients with histoplasmosis and blastomycosis have responded to therapy. There are no relapses among five evaluable responders after a mean of 9.2 months off therapy. In 512 patient months of therapy, toxicity has been minimal. Mean serum levels in patients receiving 200 mg twice daily range from 3.9 to 5.9 micrograms/ml for 8 hr after dosing, with a peak at 7 hr and wide interpatient variability. Itraconazole is well tolerated and has continued to demonstrate efficacy in the treatment of a variety of systemic and superficial mycoses.

Tolerance to and efficacy of itraconazole in treatment of systemic mycoses: preliminary results.

Twelve patients with mycotic infections were treated with itraconazole during a one-year period. Patients had the following conditions: coccidioidomycosis (three), histoplasmosis (three), mucocutaneous candidosis (two), aspergillosis (three), and urinary tract infection due to Torulopsis glabrata (one). The daily dose of itraconazole ranged from 100 to 200 mg. Ten of the 12 cases were assessable. Clinical improvement was observed in six patients, two with coccidioidomycosis, two with mucocutaneous candidosis, one with histoplasmosis, and one with aspergilloma. Four patients did not respond to therapy; two of these patients had aspergillosis, one had histoplasmosis, and one had T. glabrata infection. No adverse effects were attributable to itraconazole.