2856. Salvaging High-Value Catheters: Antifungal Lock Therapy for Candidal Central Catheter Infections in a Pediatric Cohort

Background By IDSA guidelines, therapy for central line-associated bloodstream infections (CLABSI) due to Candida species requires catheter removal and administration of systemic antifungals. Despite this, in selected cases catheter salvage is desirable. The addition of antifungal lock therapy (ALT) has been proposed in these cases, but evidence for efficacy of this approach is limited. Here we report a retrospective analysis of ALT use for CLABSI due to Candida species at a single pediatric center. Methods All events of candidal CLABSI with ALT use were identified by retrospective record review between January 1, 2008 and December 31, 2018. CLABSI was defined by the growth of Candida from at least one central blood culture. Clearance was defined as a period of 48 hours with no positive cultures. Recurrence was defined as a subsequent positive blood culture with the same fungal organism either before or after line removal. Events were classified as “early removal” vs. “retained 7 days” depending on whether the line remained in place on day 7 after the first positive culture. Results Overall, 122 qualifying CLABSI were identified, 64 (52%) were retained 7 days or more (Table 1). Overall, 59% of CLABSI met criteria for clearance prior to line removal. Lines retained 7 days were likely to also remain in place at 28 days (72%) and had a low rate of relapse (8%) within 28 days. Lines in the early removal group had lower recurrence rates within 1 year (17% vs. 42%, P = 0.005), but this difference narrowed when considering recurrence at any time (31% vs. 47%, P = 0.1) or by Kaplan–Meier analysis (Figure 1) Additional microbiological and outcome data can be found in Tables 2 and 3. Conclusion This retrospective analysis is the largest described cohort of antifungal locks for line salvage in a pediatric population to our knowledge. These findings highlight the advantages of line removal, with lower recurrence at 1 year. However, when line salvage with antifungal locks is attempted, retention and recurrence rates in the first month are favorable, and recurrence rates converge in the long-term, presumably because the underlying risk factors remain. While line removal remains the standard therapy for candidal CLABSI, we find that ALT-based line salvage may be a viable alternative. Disclosures All Authors: No reported Disclosures.

Antifungal Lock Therapy

ABSTRACTThe 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 albicansis the fourth leading cause of hospital-associated BSIs. The propensity ofC. albicansto 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 byCandidaspecies usually requires catheter removal in addition to systemic antifungal therapy. Alternatively, antimicrobial lock therapy has received significant interest and shown promise as a strategy to treat CR-BSIs due toCandidaspecies. The existingin vitro, animal, and patient data for treatment ofCandida-related CR-BSIs are reviewed. The most promising antifungal lock therapy (AfLT) strategies include use of amphotericin, ethanol, or echinocandins. Clinical trials are needed to further define the safety and efficacy of AfLT.

Rabbit Model of Candida albicans Biofilm Infection: Liposomal Amphotericin B Antifungal Lock Therapy

ABSTRACT Catheter-related infections due to Candida albicans biofilms are a leading cause of fungal nosocomial bloodstream infection. In this paper, we describe the development of a model of catheter-associated infection with C. albicans biofilms and show that antifungal lock therapy with liposomal amphotericin B is an effective treatment strategy for these infections. Silicone catheters surgically placed in New Zealand White rabbits were infected with C. albicans, and the rabbits were randomized into three groups: (i) untreated controls, (ii) liposomal amphotericin B lock, and (iii) fluconazole lock. Upon completion of therapy, blood cultures were obtained and the catheters were removed for quantitative culture and scanning electron microscopic analyses. Quantitative cultures revealed that catheters treated with liposomal amphotericin B yielded 0 CFU, which was significant compared to the untreated controls (P < 0.001) and the fluconazole-treated group (P = 0.0079). Although fluconazole treatment tended to have lower CFU compared to untreated controls, there was no difference in mean colony counts between these two groups (1.128 ± 0.764 and 1.841 ± 1.141 log10 CFU/catheter segment, respectively; P = 0.297). Scanning electron microscopy revealed abundant biofilm in the control and fluconazole groups, while the liposomal amphotericin B group was virtually cleared. These findings suggest a possible treatment strategy for the successful salvage of catheters infected with C. albicans biofilms and describe an animal model that may play an important role in the further study of C. albicans biofilm pathogenesis and evaluation of potential antibiofilm agents.