Systemic Antifungal Chemotherapy Research Articles

Retrospective analysis of fluconazole efficacy in Candida-colonized, non-neutropenic, surgical patients in long-term intensive care

The early clinical diagnosis of invasive candidiasis is difficult. Fluconazole, which has been available since the early 1990s, is a relatively atoxic intravenously applicable antimycotic agent. For this reason it has been widely used - possibly too much. The aim of this study was the retrospective critical evaluation of the efficacy of systemic antifungal chemotherapy in non-neutropenic, Candida-colonized, surgical patients in long-term intensive care. 69 patients (54 men and 15 women, aged 55.8 [range 18-87] years) of 364 patients of the anaesthesiological intensive care unit (ICU) of the University Hospital of Heidelberg in 1991 and 1992 were selected for the study. None of the 69 patients was suffering from proven invasive candidiasis according to the gold-standard criteria of positive histology, blood culture, or isolation from a sterile compartment. However, 35 of the 69 patients were systemically treated with fluconazole (on average 295 mg per day for 10.2 days intravenously). 34 patients did not receive any antifungal therapy. Retrospectively we analysed the course of the disease in both groups of patients. Furthermore, 173 serum samples of these patients were available for investigations by Western blot for anti-Candida antibodies of the immune globulin classes M and G. Both groups, antimycotically treated and untreated patients, had similar characteristics at base-line: age, sex, underlying disease, severity of the disease (APACHE II Score), and also mortality (approximately 20 % in both groups). Only times in the ICU and on mechanical ventilation were significantly enhanced in fluconazole treated patients (p values 0.0004 each). Before therapy, the fluconazole patients had significantly more often yeasts in primarily non-sterile compartments (chi (2) test 0.05). The yeasts were partly eradicated by fluconazole (32/54, 59.3 %). Anti-Candida antibodies significantly correlated with higher age (anti 47 kDa antigen, p = 0.02), but not with other, clinically, diagnostically or prognostically relevant parameters. Fluconazole in non-neutropenic, Candida-colonized, surgical patients in long-term ICU care neither improved the clinical course nor the mortality rate among these patients. These observations indicate that there was a trend of overestimating the clinical significance of Candida in this group of patients. Fluconazole therapy may be significantly reduced in such patients.

New agents for treatment of systemic fungal infections

Systemic antifungal chemotherapy is enjoying its most dynamic era. More antifungal agents are under development than ever before, including agents in entirely new classes. Major goals of current investigations are to identify compounds with a wide spectrum of activity, minimal toxicity and a high degree of target specificity. The antifungal drugs in development include new azoles (voriconazole, posaconazole (formerly SCH56592), ravuconazole [formerly BMS-207147]), lipid formulations of amphotericin B, a lipid formulation of nystatin, echinocandins (VER-002 [formerly, LY303366], caspofungin [formerly MK-991], FK463), antifungal peptides other than echinocandins and sordarin derivatives. This discussion reviews the currently available antifungal agents and summarises the developmental issues that surround these new systemic antifungal drugs.

Treatment-resistant dermatomycoses

Dermatomycoses are a common category of fungal infections affecting the skin and subcutaneous tissues. Recent advances in topical and systemic antifungal chemotherapy have provided us with satisfactory results in most of the superficial fungal infections both clinically and mycologically. Despite the efficacy of antifungal agents, however, there are dermatomycoses that do not respond to our current standard regimens of treatment. Factors concerning the treatment-resistance, such as host's underlying conditions and fungal virulence, are discussed in detail.

Vertebral osteomyelitis due to Pseudallescheria boydii

A case of primary vertebral osteomyelitis due to an opportunistic fungus, Pseudallescheria boydii, in a child with acute myeloid leukemia, is reported. To our knowledge this is the first such case in a child, and only the second reported case in the international literature of primary spinal osteomyelitis due to this organism. We discuss the problems presented by this case both in terms of diagnosis and management. We also discuss the role of surgery and systemic antifungal chemotherapy in the treatment of deep infections due to Pseudallescheria boydii.

Current role of therapy with amphotericin B.

Systemic antifungal chemotherapy frequently is more difficult to conduct than antibacterial therapy. Factors that make it difficult include, but are not limited to, common biosynthetic pathways among the eukaryotes and humans, a relative lack of agents, imprecise modes of use, general lack of standardization of in vitro susceptibility tests that have clinical correlations, and, with certain exceptions, lack of clinical correlations with in vitro results of combination antifungal chemotherapy. Amphotericin B has been available for intravenous administration for greater than 30 years and, despite its shortcomings, remains the drug of choice or reference agent in the therapy for many specific systemic fungal infections in various clinical settings. The current role of amphotericin B therapy in these situations and the need for additional controlled, comparative clinical trials with azoles, liposomal amphotericin B, and amphotericin B complex are discussed.

Infections due to Xylohypha bantiana (Cladosporium trichoides).

Thirty culture-documented cases of infection caused by Xylohypha bantiana (synonyms, Cladosporium bantianum, Cladosporium trichoides) were identified in the world literature; 26 cases involved the central nervous system (CNS) and most frequently presented as chronic headache followed by fever and hemiparesis. Phaeohyphomycosis due to X. bantiana occurs worldwide, predominantly in young males. Pharmacologic immunosuppression was not an important predisposing factor. However, four patients had a history of systemic nocardiosis or facial phaeohyphomycosis caused by Alternaria species. Chest radiography revealed no pulmonary infiltrates. Computed tomography of the brain demonstrated a mass defect, the frontal lobes being the most common sites of infection. Lumbar puncture usually demonstrated an elevated opening pressure, elevated cerebrospinal fluid protein level, hypoglycorrhachia, and cultures were negative. No preoperative clinical or laboratory features indicated CNS fungal infection. Complete neurosurgical resection of the lesion was the most important therapeutic intervention determining survival; systemic antifungal chemotherapy apparently did not influence outcome. The survival rate of 35% for all patients and of 45% for all neurosurgically treated patients was higher than had previously been reported, probably because patients dying from infections confirmed only histopathologically were excluded.

Cutaneous Chromomycosis in Renal Transplant Recipients: Successful Management in Two Cases

• Cutaneous chromomycosis occurred in two renal transplant recipients from the south central United States. Both patients have been managed successfully with surgical excision of isolated lesions, and the condition of one of these has been improved but not cured with low-dose ketoconazole therapy. Even in the immunocompromised host, localized cutaneous chromomycosis may not require more aggressive systemic antifungal chemotherapy. ( Arch Intern Med 1985;145:1036-1037)

Cutaneous Chromomycosis in Renal Transplant Recipients

Cutaneous chromomycosis occurred in two renal transplant recipients from the south central United States. Both patients have been managed successfully with surgical excision of isolated lesions, and the condition of one of these has been improved but not cured with low-dose ketoconazole therapy. Even in the immunocompromised host, localized cutaneous chromomycosis may not require more aggressive systemic antifungal chemotherapy.

Cutaneous chromomycosis in renal transplant recipients. Successful management in two cases

Cutaneous chromomycosis occurred in two renal transplant recipients from the south central United States. Both patients have been managed successfully with surgical excision of isolated lesions, and the condition of one of these has been improved but not cured with low-dose ketoconazole therapy. Even in the immunocompromised host, localized cutaneous chromomycosis may not require more aggressive systemic antifungal chemotherapy.