deoxycholic-acid and Endocarditis

In recent decades the incidence of Candida endocarditis has increased dramatically. Despite the application of surgery and antifungal therapy, Candida endocarditis remains a life-threatening infection with significant morbidity and mortality. We report a 37-year-old male drug abuser presenting with high fever, chest pain, loss of appetite and cardiac failure. His echocardiography revealed mobile large tricuspid valve vegetations. Fungal endocarditis was confirmed by culturing of the resected vegetation showing mixed growth of Candida albicans and Candida tropicalis, although three consecutive blood cultures were negative for Candida species. Phenotypic identification was reconfirmed by sequencing of the internal transcribed spacer (ITS rDNA) region. The patient was initially treated with intravenous fluconazole (6 mg kg(-1) per day), followed by 2 weeks of intravenous amphotericin B deoxycholate (1 mg kg(-1) per day). Although MICs were low for both drugs, the patient's antifungal therapy combined with valve replacement failed, and he died due to respiratory failure.

Topics: Adult; Amphotericin B; Antifungal Agents; Candida albicans; Candida tropicalis; Candidiasis; Coinfection; Deoxycholic Acid; DNA, Fungal; DNA, Ribosomal Spacer; Drug Combinations; Drug Users; Echocardiography; Endocarditis; Fatal Outcome; Fluconazole; Humans; Male; Molecular Sequence Data; Mycological Typing Techniques; Sequence Analysis, DNA; Substance-Related Disorders; Tricuspid Valve

To evaluate and compare in vivo the protective efficacy of unilamellar liposomal amphotericin B (L-AmB) with that of deoxycholate amphotericin B (D-AmB) in experimental endocarditis.. In the rabbit model of experimental Aspergillus fumigatus endocarditis, two doses of each antifungal agent (1.5 mg/kg each) were administered intravenously at 4 hours and at 30 minutes before challenge with an inoculum of A. fumigatus. Three days later, the animals were sacrificed, and the aortic vegetations were analyzed.. All 19 animals that did not receive chemoprophylaxis acquired endocarditis. In contrast, endocarditis developed in 2 of 10 animals pretreated with D-AmB (P < 0.01) and 3 of 8 animals pretreated with L-AmB (P < 0.01). Both D-AmB and L-AmB prevented the development of endocarditis due to A. fumigatus and decreased the concentration of fungi in the aortic vegetations by more than 1 log10.. In the rabbit experimental model of Aspergillus endocarditis, D-AmB and L-AmB were equally effective in reducing the incidence of the infection and the tissue burden of fungi.

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Cholagogues and Choleretics; Deoxycholic Acid; Disease Models, Animal; Endocarditis; In Vitro Techniques; Liposomes; Male; Rabbits

In the quest for safer and more effective antifungal agents, amphotericin B (AMB) has been placed in a variety of lipid preparations. In this study, we examined the efficacy of amphotericin B lipid complex (ABLC) on experimental cryptococcal meningitis and disseminated candidosis. This formulation is relatively safe compared to the parent compound, and therefore doses ten times greater than the commercial amphotericin B deoxycholate can be given to rabbits. Although at equal doses the ABLC preparation is less potent than AMB, a higher dose of ABLC was rapidly fungicidal in the contexts of both a central nervous system infection with Cryptococcus neoformans during immune suppression, and a heart and kidney infection with Candida albicans. Rapid sterilization of tissue should be a goal of antifungal drug therapy, particularly in the immune compromised host. From these studies, this AMB lipid formulation has the ability to produce rapid fungicidal activity in vivo, but it requires higher doses than AMB deoxycholate. Clinical trials in humans must examine carefully the therapeutic-toxic ratio in dose-escalation protocols to determine the optimal dosage strategy for this agent.

Topics: Amphotericin B; Animals; Blood Vessels; Candidiasis; Colony Count, Microbial; Cryptococcus neoformans; Deoxycholic Acid; Drug Combinations; Endocarditis; Kidney; Liposomes; Male; Meningitis, Cryptococcal; Rabbits