CASE REPORT Antifungal Catheter Lock Therapy for the Management of a Persistent Candida albicans Bloodstream Infection in an Adult Receiving Hemodialysis V. Paul DiMondi,1,* Mary L. Townsend,1,2 Melissa Johnson,3,4 and Michael Durkin3 1
Department of Pharmacy Practice, Campbell University College of Pharmacy and Health Sciences, Buies Creek, North Carolina; 2Department of Pharmacy, Durham VA Medical Center, Durham, North Carolina; 3Department of Medicine, Duke University School of Medicine, Durham, North Carolina; 4Department of Clinical Research, Campbell University College of Pharmacy and Health Sciences, Buies Creek, North Carolina
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. Despite receiving intravenous micafungin, she had multiple positive blood cultures for Candida albicans, which finally cleared after 7 days. Her double-lumen catheter was considered the most likely nidus of infection. Although catheter removal would have been preferred, this was not possible given her vasculopathy, history of multiple bloodstream infections, and lack of other available sites for vascular access. Catheter exchange was performed, and liposomal amphotericin B AfLT was administered in combination with intravenous micafungin for a total of 6 days. During this time, the patient experienced no discernible adverse effects secondary to AfLT. At discharge, AfLT was discontinued, and intravenous micafungin was changed to oral fluconazole. After 6 months of treatment, the patient remained culture negative and maintained her dialysis access. To our knowledge, this is the first case report of liposomal amphotericin B catheter lock therapy used to manage a persistent C. albicans bloodstream infection in an adult receiving hemodialysis. AfLT is a novel concept for treating catheterassociated fungal infections. Liposomal amphotericin B was chosen based on its favorable in vitro activity against Candida species biofilms in catheter lock environments. We identified several barriers to implementing AfLT, and these issues may prohibit the use of AfLT. This case report illustrates the benefits and challenges of managing catheter-associated fungal infections with AfLT. Further study is required to examine the efficacy, safety, and feasibility of this approach. KEY WORDS antifungal, lock, catheter, amphotericin, Candida species, biofilm. (Pharmacotherapy 2014;**(**):**–**) doi: 10.1002/phar.1433
Antifungal catheter lock therapy (AfLT) with liposomal amphotericin B has been used in the *Address for correspondence: V. Paul DiMondi, Department of Pharmacy Practice, Campbell University College of Pharmacy & Health Sciences, PO Box 1090, Buies Creek, NC 27506; e-mail: [email protected]. Ó 2014 Pharmacotherapy Publications, Inc.
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
2
PHARMACOTHERAPY Volume **, Number **, 2014
foreign bodies. Liposomal amphotericin B has demonstrated favorable in vitro activity against Candida species biofilms in a catheter lock environment. In this report, we present evidence to document the first case, to our knowledge, of a liposomal amphotericin B catheter lock solution used to manage a persistent Candida albicans bloodstream infection in an adult receiving hemodialysis. Case Report A 64-year-old woman with a history of endstage renal disease and who was receiving hemodialysis 3 times/week presented to our hospital with hypotension and a painful nonhealing traumatic right posterior calf ulcer. The patient’s medical history was extensive and complicated, but in brief, she had seven hospital admissions over the preceding 4 months for bacteremia secondary to various organisms. Unfortunately, the patient’s medical records were incomplete, and it was unclear how many of these infections were caused by Candida species. Based on the available records, her bloodstream infections were often polymicrobial and included the following pathogens: methicillin-resistant Staphylococcus aureus, Klebsiella pneumonia, coagulasenegative Staphylococcus, vancomycin-resistant Enterococcus faecium (VRE), and C. albicans. Each episode was treated with systemic antimicrobial therapy in addition to catheter removal. During the patient’s last bloodstream infection with VRE and C. albicans, her catheter was unable to be exchanged due to tenuous access. She was treated with a 14-day course of daptomycin and micafungin. During this episode, fluconazole was avoided, as the patient had a prolonged QT interval secondary to amiodarone therapy. Four months after her last infectious episode, she presented to the Duke University Hospital (Durham, NC) emergency department and was found to be afebrile and hypotensive, with a blood pressure of 85/53 mm Hg. Examination of her ulcerated right calf by ultrasound and radiograph demonstrated no evidence of deep vein thrombosis, osteomyelitis, or acute infection. Peripheral blood samples were collected for culture, and broad-spectrum antibiotic therapy with vancomycin, aztreonam (due to a penicillin allergy), and metronidazole was started empirically. The patient’s erythrocyte sedimentation rate and C-reactive protein level were elevated at 120 mm/hour and 21 mg/dl, respectively.
On hospital day 2, two sets of blood cultures were positive for C. albicans (susceptible to fluconazole, voriconazole, and caspofungin). Intravenous micafungin 100 mg/day was started, and the patient’s other antibiotics were discontinued. Over the next 5 days, she continued to have persistent fungemia, with multiple positive blood cultures for C. albicans despite appropriate antifungal therapy. Documented clearance of the patient’s blood cultures was finally achieved on the hospital day 7. The patient’s double-lumen Decathlon catheter (Bard Access Systems, Inc., Salt Lake City, UT), located in the left groin area, was considered the most likely nidus of infection. Although catheter removal would have been preferred, this was not possible given her vasculopathy, multiple bloodstream infections, and lack of other available sites for vascular access. The hemodialysis catheter was 55 cm long, with its tip terminating near the right atrium, and it was carefully exchanged over a wire on hospital day 11. Because this was not standard of care for fungal catheter infections due to the possibility of cross-contamination, antifungal lock therapy was pursued. Liposomal amphotericin B (AmBisome; Astellas Pharma, Northbrook, IL) lock therapy was initiated to locally treat any remaining infection, prevent reinfection, and inhibit biofilm formation on the newly inserted catheter. The procedure used for preparation and administration of the liposomal amphotericin lock is described in Figure 1. The lock solution was prepared according to protocol and visually inspected for any particulate matter prior to administration to the patient. Antifungal lock therapy was initiated on the same day as the catheter exchange and was continued for a total of 6 days until the patient was discharged on hospital day 16. During this time, the patient experienced no discernible adverse effects secondary to lock therapy. Her systemic antifungal was changed at discharge from micafungin to oral fluconazole 200 mg/day for ease of outpatient administration. Her QTc interval was still prolonged, but after a cardiology consultation, it was believed the benefit of fluconazole therapy outweighed the risk of an arrhythmia, and the patient was monitored clinically. The patient was discharged and prescribed a 6-month course of fluconazole therapy after catheter exchange. After discharge, surveillance blood cultures remained negative for yeast. During the next 6 months of follow-up, the patient
ANTIFUNGAL CATHETER LOCK THERAPY DiMondi et al
3
1. Reconstitute liposomal amphotericin B (AmBisome) 50-mg vial with [12 ml sterile water] according to manufacturer's instructions. Mix liposomal amphotericin B 50 mg (12.9 ml) with heparin 1200 units [1.2 ml of a 1000 unit/ml concentration] and dilute with 4.6 ml of 5% dextrose. [Final concentration = AmBisome 8 mg /3 ml and heparin 200 units/ 3 ml] 2. Dispense in two 5-ml single-use syringes and label “For catheter dwell and aspiration only. Not for IV administration.” Procedure for Nursing Note: AmBisome is NOT compatible with normal saline. 1. Instill lock solution into the lumen(s) using the appropriate volume based on the catheter type. (Decathlon catheter arterial lumen volume is 2.8 ml and venous lumen is 2.5 ml.) i. All lumens of a multilumen catheter should be instilled with the lock solution. ii. Change lock solution every 12 hours if line is not being used. 2. When the CVC is needed for medications: i. Withdraw the lock solution (Do not flush lock solution through the CVC). ii. Flush with D5W. iii. Administer the ordered medication. iv. Flush with D5W. v. Instill new lock solution. Figure 1. Protocol used for preparation and administration of the patient’s liposomal amphotericin B catheter lock solution. CVC = central venous catheter; D5W = 5% dextrose in water; IV = intravenous.
had no recurrent fungal infections and maintained her dialysis access.
economic issues should play a role in the discussion surrounding the use of AfLT.
Discussion
Agent Selection
Candida species are the fifth most common cause of hospital-acquired infections in the United States and account for 6.5% of central line– associated bloodstream infections.1 Although preventive strategies have helped to decrease the number of health care–associated infections, Candida bloodstream infections still pose significant morbidity and mortality risks.2 Catheter removal and administration of appropriate systemic antifungals are optimal for management of patients with catheter-associated fungal infections; however, inability to remove the catheter is a common challenge in clinical practice.2 Due to high failure rates with catheter retention, AfLT has been used in an attempt to salvage catheter sites. In contrast to antibiotic lock therapy, evidence evaluating AfLT is limited to in vitro and animal studies, as well as pediatric case reports. Furthermore, in addition to efficacy of the antifungal agent, other factors such as stability, compatibility, safety, logistic, and
Antimicrobial lock therapy was originally described more than 20 years ago in patients with catheter-related sepsis who were receiving home total parenteral nutrition.3 Since that time, a variety of approaches to antibiotic catheter lock therapy have been used such as salvage of infected catheters, prevention of reinfection after catheter exchange, and prophylaxis. The efficacy of antibiotic lock therapy for catheter salvage and prophylaxis has been more extensively studied than adjunctive treatment, and these strategies are currently recommended in published guidelines for select infections.4 Use of antibiotic lock therapy in combination with guidewire catheter exchange and systemic antibiotics may be an alternative management strategy for catheter-associated infections; however, to date, this intervention has not been formally evaluated in clinical studies. Conceptually, the goal of catheter lock therapy is to deliver a concentrated antibiotic solution directly to the site of infection to
4
PHARMACOTHERAPY Volume **, Number **, 2014
sterilize the catheter lumen.5 When choosing the appropriate agent for catheter lock therapy, characteristics of the infecting organism(s) and the antimicrobial agent must be considered. Antimicrobial properties to consider include the pharmacodynamic, compatibility, and stability profile of the agent selected.5 Additionally, organism-specific characteristics such as the ability of the pathogen to form biofilms should also be considered. Management of infections caused by biofilm-forming organisms can be challenging due to alterations in organism growth patterns, antibiotic resistance, and antibiotic penetration.6 Organisms such as S. aureus or Candida species are notable for their propensity to form biofilms. In addition, polymicrobial infections with Staphylococcus species and Candida species may enhance biofilm formation and affect antimicrobial activity.7 Candida are a diverse group of organisms that commonly colonize the human gastrointestinal tract, lungs, and skin. Despite over 150 Candida species being identified, less than 10% are responsible for the bulk of infections in humans.8 The bridge from colonization to infection is classically crossed in patients with either acquired or induced immunodeficiency. Historically, this is most commonly manifested as esophageal candidiasis in patients diagnosed with human immunodeficiency virus; however, advances in chemotherapeutic and immunosuppressant medications have greatly expanded the populations at risk for invasive candidiasis.9 Although C. albicans remains a common cause of invasive disease in humans, non-albicans species such as C. glabrata, C. tropicalis, C. krusei, and C. parapsilosis are becoming more frequently encountered in clinical practice.9 Unfortunately, each of these Candida species has the ability to form biofilms, and this trait has been associated with an increased risk of mortality compared with non–biofilm-forming species.10 Biofilm production in Candida species allows for adherence to foreign bodies and presents a challenging clinical scenario in patients with intravascular devices, including those receiving hemodialysis, such as our patient.6 C. albicans is most commonly associated with biofilm formation with three distinct development phases: early (0–11 hrs), intermediate (12–30 hrs), and mature (31–72 hrs).11 The development phase of the biofilm has an impact on treatment, with early and intermediate more susceptible to antifungal agents compared with mature biofilms.12 Antifungal agents have attenuated activity against
Candida biofilms due to limited biofilm penetration, lack of rapid organism growth, and selection of resistant subpopulations.13 A number of antifungal agents have been evaluated in vitro to determine their activity against Candida species biofilms, and these results have been reviewed extensively elsewhere.11 The triazole antifungals (especially fluconazole) are generally ineffective against Candida biofilms due to high minimum inhibitory concentration values encountered within the biofilm environment. In contrast, the echinocandins and amphotericin B display excellent activity against Candida biofilms. Amphotericin B deoxycholate generally has less ability to inhibit metabolic activity in the Candida biofilm environment compared with lipid formulations.14 In vitro studies evaluating antifungal lock solutions suggest that both amphotericin B and the echinocandins are options for antifungal lock therapy due to their ability to inhibit biofilm formation, suppress fungal metabolic activity, and sterilize foreign bodies.12, 15 The optimal dosing and dwell time for antifungal agents as lock therapy remains uncertain; however, in vitro studies have evaluated various scenarios. For example, two different concentrations of liposomal amphotericin B (0.2 or 1 mg/ml) were assessed against C. albicans, C. glabrata, and C. parapsilosis biofilms in vitro. Both early (12 hrs) and mature (5 days) biofilms were formed on silicone catheters and treated with liposomal amphotericin B using dwell times ranging from 4 to 24 hours. The mean inhibition of Candida species metabolic activity was similar for both concentrations (83.7% in the 0.2-mg/ml group and 85.1% in the 1-mg/ml group) irrespective of the dwell time and post-lock times. In addition, metabolic activity was inhibited for up to 48 hours after cessation of lock therapy (p
Department of Pharmacy Practice, Campbell University College of Pharmacy and Health Sciences, Buies Creek, North Carolina; 2Department of Pharmacy, Durham VA Medical Center, Durham, North Carolina; 3Department of Medicine, Duke University School of Medicine, Durham, North Carolina; 4Department of Clinical Research, Campbell University College of Pharmacy and Health Sciences, Buies Creek, North Carolina
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. Despite receiving intravenous micafungin, she had multiple positive blood cultures for Candida albicans, which finally cleared after 7 days. Her double-lumen catheter was considered the most likely nidus of infection. Although catheter removal would have been preferred, this was not possible given her vasculopathy, history of multiple bloodstream infections, and lack of other available sites for vascular access. Catheter exchange was performed, and liposomal amphotericin B AfLT was administered in combination with intravenous micafungin for a total of 6 days. During this time, the patient experienced no discernible adverse effects secondary to AfLT. At discharge, AfLT was discontinued, and intravenous micafungin was changed to oral fluconazole. After 6 months of treatment, the patient remained culture negative and maintained her dialysis access. To our knowledge, this is the first case report of liposomal amphotericin B catheter lock therapy used to manage a persistent C. albicans bloodstream infection in an adult receiving hemodialysis. AfLT is a novel concept for treating catheterassociated fungal infections. Liposomal amphotericin B was chosen based on its favorable in vitro activity against Candida species biofilms in catheter lock environments. We identified several barriers to implementing AfLT, and these issues may prohibit the use of AfLT. This case report illustrates the benefits and challenges of managing catheter-associated fungal infections with AfLT. Further study is required to examine the efficacy, safety, and feasibility of this approach. KEY WORDS antifungal, lock, catheter, amphotericin, Candida species, biofilm. (Pharmacotherapy 2014;**(**):**–**) doi: 10.1002/phar.1433
Antifungal catheter lock therapy (AfLT) with liposomal amphotericin B has been used in the *Address for correspondence: V. Paul DiMondi, Department of Pharmacy Practice, Campbell University College of Pharmacy & Health Sciences, PO Box 1090, Buies Creek, NC 27506; e-mail: [email protected]. Ó 2014 Pharmacotherapy Publications, Inc.
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
2
PHARMACOTHERAPY Volume **, Number **, 2014
foreign bodies. Liposomal amphotericin B has demonstrated favorable in vitro activity against Candida species biofilms in a catheter lock environment. In this report, we present evidence to document the first case, to our knowledge, of a liposomal amphotericin B catheter lock solution used to manage a persistent Candida albicans bloodstream infection in an adult receiving hemodialysis. Case Report A 64-year-old woman with a history of endstage renal disease and who was receiving hemodialysis 3 times/week presented to our hospital with hypotension and a painful nonhealing traumatic right posterior calf ulcer. The patient’s medical history was extensive and complicated, but in brief, she had seven hospital admissions over the preceding 4 months for bacteremia secondary to various organisms. Unfortunately, the patient’s medical records were incomplete, and it was unclear how many of these infections were caused by Candida species. Based on the available records, her bloodstream infections were often polymicrobial and included the following pathogens: methicillin-resistant Staphylococcus aureus, Klebsiella pneumonia, coagulasenegative Staphylococcus, vancomycin-resistant Enterococcus faecium (VRE), and C. albicans. Each episode was treated with systemic antimicrobial therapy in addition to catheter removal. During the patient’s last bloodstream infection with VRE and C. albicans, her catheter was unable to be exchanged due to tenuous access. She was treated with a 14-day course of daptomycin and micafungin. During this episode, fluconazole was avoided, as the patient had a prolonged QT interval secondary to amiodarone therapy. Four months after her last infectious episode, she presented to the Duke University Hospital (Durham, NC) emergency department and was found to be afebrile and hypotensive, with a blood pressure of 85/53 mm Hg. Examination of her ulcerated right calf by ultrasound and radiograph demonstrated no evidence of deep vein thrombosis, osteomyelitis, or acute infection. Peripheral blood samples were collected for culture, and broad-spectrum antibiotic therapy with vancomycin, aztreonam (due to a penicillin allergy), and metronidazole was started empirically. The patient’s erythrocyte sedimentation rate and C-reactive protein level were elevated at 120 mm/hour and 21 mg/dl, respectively.
On hospital day 2, two sets of blood cultures were positive for C. albicans (susceptible to fluconazole, voriconazole, and caspofungin). Intravenous micafungin 100 mg/day was started, and the patient’s other antibiotics were discontinued. Over the next 5 days, she continued to have persistent fungemia, with multiple positive blood cultures for C. albicans despite appropriate antifungal therapy. Documented clearance of the patient’s blood cultures was finally achieved on the hospital day 7. The patient’s double-lumen Decathlon catheter (Bard Access Systems, Inc., Salt Lake City, UT), located in the left groin area, was considered the most likely nidus of infection. Although catheter removal would have been preferred, this was not possible given her vasculopathy, multiple bloodstream infections, and lack of other available sites for vascular access. The hemodialysis catheter was 55 cm long, with its tip terminating near the right atrium, and it was carefully exchanged over a wire on hospital day 11. Because this was not standard of care for fungal catheter infections due to the possibility of cross-contamination, antifungal lock therapy was pursued. Liposomal amphotericin B (AmBisome; Astellas Pharma, Northbrook, IL) lock therapy was initiated to locally treat any remaining infection, prevent reinfection, and inhibit biofilm formation on the newly inserted catheter. The procedure used for preparation and administration of the liposomal amphotericin lock is described in Figure 1. The lock solution was prepared according to protocol and visually inspected for any particulate matter prior to administration to the patient. Antifungal lock therapy was initiated on the same day as the catheter exchange and was continued for a total of 6 days until the patient was discharged on hospital day 16. During this time, the patient experienced no discernible adverse effects secondary to lock therapy. Her systemic antifungal was changed at discharge from micafungin to oral fluconazole 200 mg/day for ease of outpatient administration. Her QTc interval was still prolonged, but after a cardiology consultation, it was believed the benefit of fluconazole therapy outweighed the risk of an arrhythmia, and the patient was monitored clinically. The patient was discharged and prescribed a 6-month course of fluconazole therapy after catheter exchange. After discharge, surveillance blood cultures remained negative for yeast. During the next 6 months of follow-up, the patient
ANTIFUNGAL CATHETER LOCK THERAPY DiMondi et al
3
1. Reconstitute liposomal amphotericin B (AmBisome) 50-mg vial with [12 ml sterile water] according to manufacturer's instructions. Mix liposomal amphotericin B 50 mg (12.9 ml) with heparin 1200 units [1.2 ml of a 1000 unit/ml concentration] and dilute with 4.6 ml of 5% dextrose. [Final concentration = AmBisome 8 mg /3 ml and heparin 200 units/ 3 ml] 2. Dispense in two 5-ml single-use syringes and label “For catheter dwell and aspiration only. Not for IV administration.” Procedure for Nursing Note: AmBisome is NOT compatible with normal saline. 1. Instill lock solution into the lumen(s) using the appropriate volume based on the catheter type. (Decathlon catheter arterial lumen volume is 2.8 ml and venous lumen is 2.5 ml.) i. All lumens of a multilumen catheter should be instilled with the lock solution. ii. Change lock solution every 12 hours if line is not being used. 2. When the CVC is needed for medications: i. Withdraw the lock solution (Do not flush lock solution through the CVC). ii. Flush with D5W. iii. Administer the ordered medication. iv. Flush with D5W. v. Instill new lock solution. Figure 1. Protocol used for preparation and administration of the patient’s liposomal amphotericin B catheter lock solution. CVC = central venous catheter; D5W = 5% dextrose in water; IV = intravenous.
had no recurrent fungal infections and maintained her dialysis access.
economic issues should play a role in the discussion surrounding the use of AfLT.
Discussion
Agent Selection
Candida species are the fifth most common cause of hospital-acquired infections in the United States and account for 6.5% of central line– associated bloodstream infections.1 Although preventive strategies have helped to decrease the number of health care–associated infections, Candida bloodstream infections still pose significant morbidity and mortality risks.2 Catheter removal and administration of appropriate systemic antifungals are optimal for management of patients with catheter-associated fungal infections; however, inability to remove the catheter is a common challenge in clinical practice.2 Due to high failure rates with catheter retention, AfLT has been used in an attempt to salvage catheter sites. In contrast to antibiotic lock therapy, evidence evaluating AfLT is limited to in vitro and animal studies, as well as pediatric case reports. Furthermore, in addition to efficacy of the antifungal agent, other factors such as stability, compatibility, safety, logistic, and
Antimicrobial lock therapy was originally described more than 20 years ago in patients with catheter-related sepsis who were receiving home total parenteral nutrition.3 Since that time, a variety of approaches to antibiotic catheter lock therapy have been used such as salvage of infected catheters, prevention of reinfection after catheter exchange, and prophylaxis. The efficacy of antibiotic lock therapy for catheter salvage and prophylaxis has been more extensively studied than adjunctive treatment, and these strategies are currently recommended in published guidelines for select infections.4 Use of antibiotic lock therapy in combination with guidewire catheter exchange and systemic antibiotics may be an alternative management strategy for catheter-associated infections; however, to date, this intervention has not been formally evaluated in clinical studies. Conceptually, the goal of catheter lock therapy is to deliver a concentrated antibiotic solution directly to the site of infection to
4
PHARMACOTHERAPY Volume **, Number **, 2014
sterilize the catheter lumen.5 When choosing the appropriate agent for catheter lock therapy, characteristics of the infecting organism(s) and the antimicrobial agent must be considered. Antimicrobial properties to consider include the pharmacodynamic, compatibility, and stability profile of the agent selected.5 Additionally, organism-specific characteristics such as the ability of the pathogen to form biofilms should also be considered. Management of infections caused by biofilm-forming organisms can be challenging due to alterations in organism growth patterns, antibiotic resistance, and antibiotic penetration.6 Organisms such as S. aureus or Candida species are notable for their propensity to form biofilms. In addition, polymicrobial infections with Staphylococcus species and Candida species may enhance biofilm formation and affect antimicrobial activity.7 Candida are a diverse group of organisms that commonly colonize the human gastrointestinal tract, lungs, and skin. Despite over 150 Candida species being identified, less than 10% are responsible for the bulk of infections in humans.8 The bridge from colonization to infection is classically crossed in patients with either acquired or induced immunodeficiency. Historically, this is most commonly manifested as esophageal candidiasis in patients diagnosed with human immunodeficiency virus; however, advances in chemotherapeutic and immunosuppressant medications have greatly expanded the populations at risk for invasive candidiasis.9 Although C. albicans remains a common cause of invasive disease in humans, non-albicans species such as C. glabrata, C. tropicalis, C. krusei, and C. parapsilosis are becoming more frequently encountered in clinical practice.9 Unfortunately, each of these Candida species has the ability to form biofilms, and this trait has been associated with an increased risk of mortality compared with non–biofilm-forming species.10 Biofilm production in Candida species allows for adherence to foreign bodies and presents a challenging clinical scenario in patients with intravascular devices, including those receiving hemodialysis, such as our patient.6 C. albicans is most commonly associated with biofilm formation with three distinct development phases: early (0–11 hrs), intermediate (12–30 hrs), and mature (31–72 hrs).11 The development phase of the biofilm has an impact on treatment, with early and intermediate more susceptible to antifungal agents compared with mature biofilms.12 Antifungal agents have attenuated activity against
Candida biofilms due to limited biofilm penetration, lack of rapid organism growth, and selection of resistant subpopulations.13 A number of antifungal agents have been evaluated in vitro to determine their activity against Candida species biofilms, and these results have been reviewed extensively elsewhere.11 The triazole antifungals (especially fluconazole) are generally ineffective against Candida biofilms due to high minimum inhibitory concentration values encountered within the biofilm environment. In contrast, the echinocandins and amphotericin B display excellent activity against Candida biofilms. Amphotericin B deoxycholate generally has less ability to inhibit metabolic activity in the Candida biofilm environment compared with lipid formulations.14 In vitro studies evaluating antifungal lock solutions suggest that both amphotericin B and the echinocandins are options for antifungal lock therapy due to their ability to inhibit biofilm formation, suppress fungal metabolic activity, and sterilize foreign bodies.12, 15 The optimal dosing and dwell time for antifungal agents as lock therapy remains uncertain; however, in vitro studies have evaluated various scenarios. For example, two different concentrations of liposomal amphotericin B (0.2 or 1 mg/ml) were assessed against C. albicans, C. glabrata, and C. parapsilosis biofilms in vitro. Both early (12 hrs) and mature (5 days) biofilms were formed on silicone catheters and treated with liposomal amphotericin B using dwell times ranging from 4 to 24 hours. The mean inhibition of Candida species metabolic activity was similar for both concentrations (83.7% in the 0.2-mg/ml group and 85.1% in the 1-mg/ml group) irrespective of the dwell time and post-lock times. In addition, metabolic activity was inhibited for up to 48 hours after cessation of lock therapy (p
