Antifungal lock therapy

Candida albicans is a major cause of catheter-related bloodstream infections and is associated with high morbidity and mortality. Due to the propensity of C. albicans to form drug-resistant biofilms, the current standard of care includes catheter removal; however, reinsertion may be technically challenging or risky. Prolonged exposure of an antifungal lock solution within the catheter in conjunction with systemic therapy has been experimentally attempted for catheter salvage. Previously, we demonstrated excellent in vitro activity of micafungin, ethanol, and high-dose doxycycline as single agents for prevention and treatment of C...

OBJECTIVES: The effectiveness of anidulafungin versus liposomal amphotericin B (LAmB) for treating experimental Candida parapsilosis catheter-related infection by an antifungal-lock technique was assessed. METHODS: Two clinical strains of C. parapsilosis (CP12 and CP54) were studied. In vitro studies were used to determine the biofilm MICs (MBIC50 and MBIC90) by XTT reduction assay and LIVE/DEAD biofilm viability for anidulafungin and LAmB on 96-well microtitre polystyrene plates and silicone discs...

We conducted a prospective pilot study to evaluate the potential role of combined systemic antifungal and liposomal amphotericin B lock therapy in children with intestinal insufficiency with fungal catheter-related bloodstream infections whose central venous catheters had not been removed. Our results provide supportive evidence for the conduct of larger clinical trials to confirm the efficacy and safety of this approach.

Candida spp. usually colonize ulcerative lesions of atrophic mucosa in patients with chemotherapy-induced oral mucositis inducing severe inflammation. The spread of antifungal-resistant strains strongly encouraged the search of complementary or alternative therapeutic strategies to cure inflamed mucosa. In this paper, we studied the effects of a near-infrared (NIR) laser system with dual-wavelength emission (808 nm + 904 nm) on the survival and inflammatory potential of C. albicans, C. glabrata, and C. parapsilosis...

Intravascular catheters are among the most commonly inserted medical devices and they are known to cause a large number of catheter related bloodstream infections (BSIs). Biofilms are associated with many chronic infections due to the aggregation of microorganisms. One of these organisms is the fungus Candida albicans. It has shown to be one of the leading causes of catheter-related BSIs. The presence of biofilm on intravascular catheters provide increased tolerance against antimicrobial treatments, thus alternative treatment strategies are sought...

OBJECTIVES: The objective of this study was to clarify the antifungal properties of cerium, a lanthanide member, against Candida species. A comprehensive study with planktonic and sessile cells was performed. The ability of cerium nitrate (CN) to impair in vitro and in vivo biofilm formation was evaluated and its potential use in biofilm treatment was also evaluated. METHODS: Forty-eight clinical isolates of different Candida species and the type strain ATCC 90028 were tested according to the protocol M27-A3...

BACKGROUND: The ability to form biofilm enables Candida spp. to cause catheter-related candidaemia. The use of agents with in vitro activity against Candida albicans biofilms, such as micafungin, could obviate catheter removal. The metabolic activity of C. albicans biofilms is strain-dependent, and cell wall formation is thought to be more prominent in biofilms showing high metabolic activity. METHODS: We studied the antifungal activity of micafungin against 265 C...

Antifungal catheter lock therapy (AfLT) with liposomal amphotericin B has been used in the treatment of pediatric central line infections caused by Candida species; however, reports describing the use of liposomal amphotericin B lock therapy in the adult hemodialysis patient population are lacking. Management of central line-associated candidemia with systemic therapy alone is often challenging due to the propensity of Candida species to form biofilms on foreign bodies. We describe a 64-year-old woman who was receiving hemodialysis 3 times/week and was hospitalized with persistent fungemia...

Newborn infants in critical conditions require a permanent intra-venous line to allow for the administration of fluids, parenteral nutrition and drugs. The use of central venous catheters, however, is associated with an increased risk of infections, leading to prolongation of length of stay and higher hospitalization costs, particularly in extremely preterm infants. Dwell time is a significant factor for complications, with a predicted risk of catheter related infections of about 4 per 1000 catheter-days. To reduce the incidence of complications, several requirements must be met, including adequate staff and resources to provide education, training, and quality improvement programs, within a culture of communication and teamwork...

Microbial biofilms play an essential role in several infectious diseases and are defined as extensive communities of sessile organisms irreversibly associated with a surface, encased within a polysaccharide-rich extracellular matrix (ECM), and exhibiting enhanced resistance to antimicrobial drugs. Forming a biofilm provides the microbes protection from environmental stresses due to contaminants, nutritional depletion, or imbalances, but is dangerous to human health due to their inherent robustness and elevated resistance...

So-called lock therapy, consisting of high concentrations of antimicrobials instilled into the lumen of the catheter, has been suggested avoid central venous catheter removal during fungal infection. We report a baby who developed catheter-related candidemia. Systemic antifungal treatment did not resolve the candidemia. Lock therapy with 0.3 mL of ethanol 70% and micafungin sodium 5 mg/L was added to the therapy, and blood cultures became sterile.

PURPOSE: Published stability and compatibility data on a growing array of solutions used for antimicrobial lock therapy (ALT) are reviewed. SUMMARY: ALT involves the instillation of a highly concentrated antimicrobial, often in combination with an anticoagulant, into a central venous catheter (CVC) lumen; this technique is often used for prophylaxis after CVC insertion or as an adjunctive treatment in cases of central line-associated bloodstream infection (CLABSI) if catheter removal is not feasible...

BACKGROUND & AIMS: Anti-infective lock therapy is a treatment strategy in conjunction with systemic antifungal agents for the treatment of intravascular catheter infections caused by fungi. In this study, the optimal dosage and dwell time of ethanol lock solution (ELS) effective against catheters infected by Candida species were assessed. METHODS: Biofilm forming isolates of Candida albicans, Candida parapsilosis and Candida tropicalis was used as the study isolates...

Antimicrobial catheter lock therapy is practiced to prevent lumenal-sourced infections of central venous catheters. Citrate has been used clinically as an anticoagulant in heparin-free catheter locks. Ethanol has also been widely studied as an antimicrobial lock solution component. This study reports on the synergy of glyceryl trinitrate (GTN) with citrate and ethanol in rapidly eradicating methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans biofilms in an in vitro model for catheter biofilm colonization...

Biofilms formed by Candida albicans bloodstream isolates on catheters are an important clinical problem. Devising chemotherapeutic strategies to treat these in situ is an attractive option. We report here that liposomal amphotericin effectively kills C. albicans biofilms rapidly (12 h) and effectively (>90%) in a dose-dependent manner, whereas caspofungin displays an inverse concentration-dependent effect. This study has implications for considering the effective doses of antifungal agents used for catheter lock therapy...

Device-related bacteremia is the most frequent complication in patients with indwelling central venous catheter. Guidelines recommend treatment based on epidemiology and antimicrobial susceptibility tests, but catheter removal is advocated in the presence of particular clinical conditions or pathogen isolations. Anti-infective drugs might become less effective in the presence of pathogens with increases in minimal inhibitory concentrations or slime production, and sometimes catheter removal is not feasible, for example, in patients with limited vascular sites or in the presence of life-threatening clinical conditions...

Ethanol lock therapy has been implemented to prevent infections of central venous catheters as well as to treat infections. Fungal catheter-associated blood stream infections are historically more difficult to treat and have required removal of central venous catheters. We report the largest case series to date, successfully treating 5 of 7 fungal catheter-associated blood stream infections with ethanol lock therapy and systemic echinocandin administration.

The widespread use of intravascular devices, such as central venous and hemodialysis catheters, in the past 2 decades has paralleled the increasing incidence of catheter-related bloodstream infections (CR-BSIs). Candida albicans is the fourth leading cause of hospital-associated BSIs. The propensity of C. albicans to form biofilms on these catheters has made these infections difficult to treat due to multiple factors, including increased resistance to antifungal agents. Thus, curing CR-BSIs caused by Candida species usually requires catheter removal in addition to systemic antifungal therapy...

Fungal biofilms associated with inserted medical devices such as catheters, represent a major risk factor for candidemia. In addition, these biofilm yeasts show a decreased susceptibility to antifungal agents. Recently, a new therapeutic approach has emerged, the "lock therapy", based on the use of high concentrations of antimicrobials, instilled into the lumen of the catheter and left in place for 8 to 12 h. In vitro or in vivo studies have evaluated the interest of antifungal locks using amphotericin B, an azole or echinocandins...

Coccidioidomycosis in solid organ transplant recipients most often occurs as a result of primary infection or reactivation of latent infection. Herein, we report a series of cases of transplant-related transmission of coccidioidomycosis from a single donor from a non-endemic region whose organs were transplanted to 5 different recipients. In all, 3 of the 5 recipients developed evidence of Coccidioides infection, 2 of whom had disseminated disease. The degree of T-cell immunosuppression and timing of antifungal therapy initiation likely contributed to development of disease and disease severity in these recipients...