Fluconazole for Life-Threatening Fungal Infections in Patients Who Cannot Be Treated with Conventional Antifungal Agents

Robinson, Patrick; Knirsch, Anthony K.; Joseph, John A.

doi:10.1093/clinids/12.supplement_3.s349

Cited by 83 publications

(27 citation statements)

References 58 publications

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“…Solomkin et al [17] suggest that a total dose of 6 mg-8 mg/kg may be sufficient to clear fungemia in postsurgical patients [17]. Ex-perience with the new imidazole drugs for treatment of systemic candidiasis and candidemia is limited [18,19].…”

Section: Discussionmentioning

confidence: 99%

Candidemia from a Urinary Tract Source: Microbiological Aspects and Clinical Significance

Ang

Telenti

King

et al. 1993

Clinical Infectious Diseases

124

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Twenty-six cases of candidemia associated with a well-defined urinary tract source were retrospectively identified and reviewed. Urinary tract abnormalities were present in 23 of 26 patients (88%), 19 (73%) of whom had urinary tract obstruction. Nineteen patients had undergone urinary tract procedures before the onset of candidemia. Episodes of candidemia were brief and low-grade in intensity (median duration, 1 day; median colony count, 1.5 cfu/10 mL of blood).Only eight patients (31%) received >500 mg of amphotericin B. There were five in-hospital deaths (19%); two of these deaths were attributed to candidiasis. No late complications of candidemia were documented for the surviving patients. Patients with urologic pathology and candiduria who undergo surgery or manipulation of the urinary tract are at significant risk for candidemia, and further studies should examine the issue of administration of prophylaxis to this group.Candiduria often presents a dilemma to the clinician, as it may represent colonization or infection. The prevalence of candiduria has been estimated at 0.2%-6% [1, 2] among asymptomatic volunteers and at 6.5%-20% among hospitalized patients [2,3]. Despite the high prevalence of candiduria, it is not well known which patients will develop complications such as candidemia. For patients in the critical care setting, the mortality associated with urine cultures positive for Candida species was 50%, as opposed to 19% for such patients without cultures positive for Candida [4]. On the other hand, Schonebeck and Ansehn [5] observed 40 patients with candiduria that persisted from 1 to 12 months and found that the infection spontaneously resolved in the majority of patients, although five remained candiduric after >12 months. The goal of this retrospective study was to describe the characteristics of candidemia arising in patients with a well-defined urinary tract source of infection. Materials and MethodsAll patients with blood cultures positive for Candida species at the Mayo Clinic from March 1985 to December 1987 were identified through a review of microbiological records. Patients with candidemia were eligible for inclusion in the study if they had concomitant candiduria and no alternative source of candidemia. Candiduria was defined as the pres- ence of Candida species in urine cultures or the presence of yeast in the urine on microscopy. Recovery of Candida species from skin, sputum, or mucous membranes did not constitute criteria for exclusion. All in-patient and out-patient records were reviewed, and the following data were recorded: age, sex, underlying diseases, potential risk factors, clinical and laboratory features, radiological study findings, pathology reports, and treatment and outcome. Blood cultures were done for patients if they had fever or if the clinical circumstances suggested the possibility of systemic infection.The onset of fungemia was defined as the first day on which blood cultures positive for Candida were obtained. Potential risk factors were defined as: (1) administra...

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Section: Discussionmentioning

confidence: 99%

Candidemia from a Urinary Tract Source: Microbiological Aspects and Clinical Significance

Ang

Telenti

King

et al. 1993

Clinical Infectious Diseases

124

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“…Response rates ranged from Amphotericin B transplantation 100% (6) to 78% (14) or 71% (15). Relapse rates ranged from 46% (6) to 27% (14).…”

Section: * Corresponding Authormentioning

confidence: 99%

“…Relapse rates ranged from 46% (6) to 27% (14). Liver function abnormalities were observed with incidences of 6% (6) and 5% (15).…”

Section: * Corresponding Authormentioning

confidence: 99%

Fluconazole in the treatment of candidiasis in immunocompromised children

Viscoli

Castagnola

Fioredda

et al. 1991

Antimicrob Agents Chemother

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Fluconazole, a new triazole derivative, was evaluated in a pilot study of 34 episodes of candidiasis in 24 children. All the patients had predisposing conditions, such as human immunodeficiency virus infection, cancer, organ or bone marrow transplantation, neonatal age and malnutrition, and obstructive uropathy. The drug was administered at 6 mg/kg (body weight) once daily either orally or intravenously. Two patients with fungemia due to Candida parapsilosis required an increased dosage of 12 mg/kg. Clinical and microbiological success was achieved in 30 of 34 cases (88%). Drug-related transaminase increases were observed in two cases (6%). Fluconazole may represent an effective alternative to amphotericin B in the treatment of candidiasis in children. Comparative trials are necessary to assess optimal dosages and efficacy.

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“…Some of these patients were given concurrent systemic oral antifungal therapy with ketoconazole or flucytosine (5FC) to treat possible subclinical systemic infection. Despite the reported successful outcome, the relative efficacies of these alternative therapies remain to be determined.Fluconazole, a triazole derivative, is a new antifungal agent that has a broad spectrum of activity against most Candida species and other fungal organisms (13,34,35). It can be administered orally or intravenously and is associated with minimal systemic side effects.…”

mentioning

confidence: 99%

“…Fluconazole, a triazole derivative, is a new antifungal agent that has a broad spectrum of activity against most Candida species and other fungal organisms (13,34,35). It can be administered orally or intravenously and is associated with minimal systemic side effects.…”

mentioning

confidence: 99%

Treatment of exogenous Candida endophthalmitis in rabbits with oral fluconazole

Park

D’Amico

Paton

et al. 1995

Antimicrob Agents Chemother

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We investigated the efficacy of oral fluconazole, alone or in combination with oral flucytosine (5FC), in treating Candida endophthalmitis using a rabbit model. Albino rabbits were infected with an intravitreal inoculation of 1,000 CFU of susceptible Candida albicans and randomized 5 days later to receive treatment with oral fluconazole alone (80 mg/kg of body weight per day), a combination of fluconazole and 5FC (100 mg/kg/12 h), or no treatment. The treatment effect was assessed at 2 and 4 weeks after therapy by funduscopy, quantitative vitreous culture, and histopathology. Intravitreal levels of fluconazole, 2 to 24 h after the first dose, were measured to be >10 times the MIC of the drug for C. albicans. Among rabbits treated with fluconazole for 2 weeks, 67% had a >90% reduction in fungal load (P < 0.05) and 33% were sterile. After 4 weeks, all had a >99% reduction in fungal load (P < 0.05) and 75% were sterile (P ‫؍‬ 0.01). This treatment effect was unchanged 4 weeks after discontinuation of fluconazole. Among rabbits treated with fluconazole and 5FC for 2 weeks, 67% died during therapy. Among the surviving rabbits, 75% had a >90% reduction in fungal load (P < 0.05) and 25% were sterile. We conclude that oral fluconazole may be useful for treatment of Candida endophthalmitis. Addition of 5FC was associated with high toxicity and minimal additional antifungal effect in our rabbit model. Intraocular fungal infection can result from an exogenous inoculation of the microorganism, as in posttraumatic or postoperative endophthalmitis, or from an endogenous source, as in patients with fungemia. Fungal endophthalmitis accounts for 12% of all cases of infectious endophthalmitis and is a leading cause of endogenous infectious endophthalmitis (29). The most common cause of fungal endophthalmitis is Candida albicans.Traditionally, the commonly used therapy for fungal endophthalmitis consists of intravenous amphotericin B, used alone or in combination with vitrectomy and intravitreal injection of amphotericin B (1, 8, 14-16, 20, 22, 23). Although intravenous amphotericin B therapy is often effective for treatment of chorioretinitis associated with fungal endophthalmitis, treatment failure can occur in eyes with advanced endophthalmitis with marked vitreous infiltrates due to the poor penetration of the drug into the vitreous (8). In addition, systemic administration of the drug requires prolonged hospitalization and is associated with unpleasant and potentially dangerous side effects. Treatment efficacy for advanced endophthalmitis may be enhanced by combining systemic amphotericin B therapy with vitrectomy and intravitreal amphotericin B injections, but such procedures are associated with potential morbidity.For these reasons, the current advocated treatment for fungal endophthalmitis is controversial, and the therapy often is individualized on the basis of the severity of the endophthalmitis (8). In patients with endogenous Candida endophthalmitis without evidence of systemic infection, vitrectomy alone or vitrectomy...

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Fluconazole for Life-Threatening Fungal Infections in Patients Who Cannot Be Treated with Conventional Antifungal Agents

Cited by 83 publications

References 58 publications

Candidemia from a Urinary Tract Source: Microbiological Aspects and Clinical Significance

Candidemia from a Urinary Tract Source: Microbiological Aspects and Clinical Significance

Fluconazole in the treatment of candidiasis in immunocompromised children

Treatment of exogenous Candida endophthalmitis in rabbits with oral fluconazole

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