amphotericin-b--deoxycholate-drug-combination and Candidemia

There are a variety of diseases, from local mucous membrane infections to invasive systemic infections, that are caused by Candida species. As a causative agent, Candida albicans is the most common; however, the other Candida species can also cause the same clinical syndromes. Most invasive fungal infections in children occur in the hospital setting. Candidemia is a serious condition associated with high morbidity and mortality and increased healthcare costs in pediatric patients. Children at the highest risk are those with prolonged intensive care unit stays, reduced immune function, recent surgery, prior bacterial infection, prior use of antibiotics and/or corticosteroids and other immunosuppressive agents, as well as use of a central venous catheter, total parenteral nutrition, mechanical ventilation and dialysis. Positive blood culture is the gold standard of candidemia; it should not be accepted as contamination or colonization in children with an intravascular catheter. However, in oropharyngeal or vulvovaginal candidiasis, culture of lesions is rarely indicated unless the disease is recalcitrant or recurrent. Recovery of Candida from the sputum should usually be considered as colonization and should not be treated with antifungal therapy. Antigen and antibody detecting tests are evaluated in invasive Candida infections; however, there are no published results in children, and their roles in diagnosis are also unclear. For the therapy of invasive Candida infections in non-neutropenic patients, fluconazole or an echinocandin is usually recommended. Alternatively, amphotericin B deoxycholate or lipid formulations of amphotericin B can also be used. The recommended therapy of Candida meningitis is amphotericin B combined with flucytosine. The combination therapy for Candida infections is usually not indicated. Prophylaxis in non-neonatal, immunocompetent children is not recommended.

Topics: Amphotericin B; Antifungal Agents; Candida; Candidemia; Catheter-Related Infections; Child; Cross Infection; Deoxycholic Acid; Drug Combinations; Echinocandins; Fluconazole; Flucytosine; Humans; Infant, Newborn; Intensive Care Units; Leukocyte Count; Mycological Typing Techniques; Neutrophils; Survival Rate; United States

Candida parapsilosis produces biofilm, which colonizes catheters and other invasive medical devices that are manipulated by health care workers. In previous studies, C. parapsilosis in vitro biofilms have exhibited high resistance rates against conventional antifungals, but susceptibility to both echinocandins and lipid formulations of amphotericin B (lipid complex and liposomal). However, a recent study showed good activity of amphotericin B deoxycholate on the biomass of C. parapsilosis biofilms. Although moderate activity of echinocandins has been demonstrated against low metabolic activity biofilms of C. parapsilosis, few studies have analyzed the action of these drugs on high metabolic activity biofilms. Moreover, high biofilm-forming isolates have been associated with central venous catheter-related fungemia outbreaks and higher mortality rates. Therefore, it is relevant to verify the activity of the main antifungal drugs against high metabolic activity biofilms of C. parapsilosis. Our study aimed to evaluate the in vitro activity of amphotericin B deoxycholate, anidulafungin, caspofungin, and micafungin against high biofilm-forming and high metabolic activity clinical isolates of C. parapsilosis. Our results showed good activity of amphotericin B against C. parapsilosis biofilms, but none of the echinocandin drugs was effective. This suggests that amphotericin B deoxycholate may be a better choice than echinocandins for the treatment of biofilm-associated infections by C. parapsilosis, mainly in countries with insufficient health care resources to purchase lipid formulations of amphotericin B. These results warn of the possibility of persistent catheter-related candidemia caused by high biofilm-forming C. parapsilosis strains when treated with echinocandin drugs.

Topics: Amphotericin B; Antifungal Agents; Biofilms; Candida parapsilosis; Candidemia; Candidiasis; Catheter-Related Infections; Deoxycholic Acid; Drug Combinations; Drug Evaluation, Preclinical; Echinocandins; Humans; Microbial Sensitivity Tests

Candida sp. osteoarticular infection is rare and most often due to hematogenous seeding during an episode of candidemia in immunocompromised patients. However, the diagnosis can be delayed in patients with subtle symptoms and signs of joint infection without a concurrent episode of candidemia.. A 75-year-old woman presented with a three-year history of pain and swelling of the left knee. Candida pelliculosa was detected from the intraoperative tissue when the patient had undergone left total knee arthroplasty 32 months ago, but no antifungal treatment was performed. One year after the total knee arthroplasty, C. pelliculosa was repeatedly isolated from the left knee synovial fluid and antifungal treatment comprising amphotericin B deoxycholate and fluconazole was administered. However, joint infection had extended to the adjacent bone and led to progressive joint destruction. The patient underwent surgery for prosthesis removal and received prolonged antifungal treatment with micafungin and fluconazole.. This case shows that C. pelliculosa, an extremely rare non-Candida albicans sp., can cause fungal arthritis and lead to irreversible joint destruction owing to delayed diagnosis and treatment.

Topics: Aged; Amphotericin B; Antifungal Agents; Arthritis, Infectious; Arthroplasty, Replacement, Knee; Candida; Candidemia; Candidiasis; Deoxycholic Acid; Device Removal; Drug Combinations; Female; Fluconazole; Humans; Intraoperative Care; Joint Prosthesis; Knee; Micafungin; Osteomyelitis

Candida species are the leading causes of invasive fungal infection among hospitalized patients and are responsible for major economic burdens. The goals of this study were to estimate the costs directly associated with the treatment of candidemia and factors associated with increased costs, as well as the impact of first-line antifungal agents on the outcomes and costs. A retrospective study was conducted in a sample of 199 patients from four university-affiliated tertiary care hospitals in Korea over 1 year. Only costs attributable to the treatment of candidemia were estimated by reviewing resource utilization during treatment. Risk factors for increased costs, treatment outcome, and hospital length of stay (LOS) were analyzed. Approximately 65% of the patients were treated with fluconazole, and 28% were treated with conventional amphotericin B. The overall treatment success rate was 52.8%, and the 30-day mortality rate was 47.9%. Hematologic malignancy, need for mechanical ventilation, and treatment failure of first-line antifungal agents were independent risk factors for mortality. The mean total cost for the treatment of candidemia was $4,743 per patient. Intensive care unit stay at candidemia onset and antifungal switch to second-line agents were independent risk factors for increased costs. The LOS was also significantly longer in patients who switched antifungal agents to second-line drugs. Antifungal switch to second-line agents for any reasons was the only modifiable risk factor of increased costs and LOS. Choosing an appropriate first-line antifungal agent is crucial for better outcomes and reduced hospital costs of candidemia.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Antifungal Agents; Candidemia; Deoxycholic Acid; Drug Combinations; Female; Humans; Itraconazole; Male; Middle Aged; Retrospective Studies