Antifungal Locks to Treat Fungal-related Central Line Infections
Condition: Central Line Fungal Infections
MeSH terms: Infections; Mycoses
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to evaluate the usefulness of antifungal lock therapy with
      liposomal amphotericin B (Ambisome), in combination with systemic antifungal(s), in patients
      with catheter-related blood stream infections with fungal organisms, whose catheter has not
      been removed because of the continuing critical need for central line access. The primary
      group of potential patients will be those with intestinal insufficiency, including post-op
      small bowel transplant recipients.

      The recommendation of the Infectious Disease Society of America (IDSA) is to remove all
      catheters with fungal infections and treat systemically for 14 days after the last positive
      culture. However, in certain intestinal failure patients, removal of an infected line might
      significantly reduce or eliminate intravenous (IV) access and create a life threatening
      situation. Thus, the investigators' aim is to determine the usefulness of antifungal lock
      therapy in intestinal failure patients whose catheter has not been removed. The
      investigators' hope is to salvage central line catheters rather than to remove them.
    

Detailed description: 
      This is a descriptive study in intestinal failure patients with catheter-related blood stream
      infections (CRBSI) with fungal organisms. At present, the recommendation of the Infectious
      Disease Society of America (IDSA) is to remove all catheters with fungal infections and treat
      systemically for 14 days after the last positive culture (2). However, in intestinal failure
      patients who have limited IV access, removal of a line infected with Candida albicans,
      although recommended, might significantly reduce intravenous access and create a life
      threatening situation. Thus, the purpose of this study is to evaluate the use of antifungal
      lock therapy with liposomal amphotericin B (Ambisome) in combination with systemic antifungal
      therapy in patients with fungal CRBSI, whose catheter has not been removed because of the
      continuing critical need for central line access. The research methods are as follows:

        1. Study patients will consist of in-patients hospitalized at Children's Hospital of
           Pittsburgh. From our intestinal failure patients followed by GI, Transplant, and
           Pediatric Surgical Services, we plan to enroll 25 patients. In addition, other patients
           with similar concerns regarding limited central venous access with catheter-related
           candidal bloodstream infection may also be considered for this protocol.

        2. The primary group of potential patients in the study will be patients with intestinal
           insufficiency, including post-op small bowel recipients, whose intravenous access is
           limited. Thus, when a fungal CRBSI is suspected, retention of the CVC will be highly
           desirable. Additional subjects potentially eligible for this study would include
           children with cancer, those status-post bone marrow transplant, etc. who have limited
           central venous access and have a documented catheter-related bloodstream infection
           secondary to candida.

        3. Once the fungal infection is established, the patient will be approached to participate
           in the study. The investigator(s) will fully explain the study and its benefits and
           risks to the patient and/or parent or guardian (if legally appointed for research) and
           consent and assent will be obtained.

        4. Upon enrollment, antifungal therapy will be instituted consisting of both systemic and
           antifungal lock therapy.

           A. Ambisome at a dose of 3-5 mg/kg/day (or other appropriate antifungal based upon
           standard of care) will be administered intravenously B. Antifungal lock therapy with
           Ambisome will be administered. It consists of the placing up to 2.3 ml (based upon
           specific catheter types and volumes) of concentrated Ambisome into the infected CVC and
           allowing it to dwell uninterruptedly for 8 to 12 hours per day. The concentration of
           Ambisome is 2 mg/ml in sterile water (4).

        5. Patients enrolled in the study will receive routine clinical care as in-patients of CHP
           and be monitored appropriately from an infectious disease perspective including daily
           blood cultures. Patients will be examined clinically for evidence of fungal-related
           complications (e.g., septic arthritis, endocarditis, etc.).

        6. The duration of antifungal lock therapy (in addition to IV systemic antifungal therapy)
           will be 10-14 days.

        7. After 5 days of antifungal lock therapy, the patient with a persistently positive fungal
           blood culture will be deemed a failure and antifungal lock therapy will be discontinued.
           There will be no further antifungal lock therapy permissible via this protocol and data
           collection for the patient will be completed as soon as possible. The primary service
           will be responsible for the removal of the line.

        8. With successful lock therapy, additional blood cultures through the catheter will be
           obtained on day 5 and day 30 (or later if subject is still on systemic antifungal
           agents) post antifungal lock for a test of cure.

             -  If a patient has a recurrence of fungal infection on culture on day 5 or day 30
                post antifungal lock, pulse field gel electrophoresis will be performed on both the
                original and new isolate to determine if the fungal organism is the same.

             -  If the organism is the same based upon electrophoretic analysis, treatment will be
                deemed a failure

             -  If the organism is not the same, then another source for the infection will be
                investigated.

        9. Since the standard of care would have been to remove the CVC, the primary end point of
           the study will be the number and percent of patients who successfully received
           antifungal lock therapy, i.e., those patients with at least 2 negative fungal cultures
           before the completion of 5 days of antifungal lock therapy and whose CVCs were not
           removed. Secondary endpoints will include the number of days before the cultures become
           negative; the development of fungal-related complications (e.g., septic arthritis,
           endocarditis, etc.); and the development of recurrent candidemia on day 5 and day 30
           post antifungal lock therapy.

       10. When medically appropriate, subjects may be discharged to complete their Ambisome® lock
           therapy at home. Instructions/training on how to administer lock therapy will be
           provided to the parents, guardian, or subject and contact with the research coordinator
           will be maintained while the patient is at home.

       11. A patient registry will be established and offered to all subjects with central line
           fungal infections treated with Ambisome® locks.
    

Intervention name(s): amphotericin B liposomal (Ambisome)
Intervention type(s): Drug
Intervention description(s): After enrollment, antifungal therapy will be instituted consisting of both systemic and antifungal lock therapy. Systemic therapy will be amphotericin B liposomal (Ambisome) administered IV in a dose of 3-5 mg/kg/day (or other antifungal based upon standard of care) combined with antifungal lock therapy. The antifungal lock therapy consists of placing sufficient amphotericin B liposomal (Ambisome [2 mg/ml]) lock solution into the infected central venous catheter (CVC) and allowing it to dwell uninterruptedly for 8 to 12 hours per day for 10-14 days (largest CVC = 2.3 mL).
Other intervention name(s): Ambisome
Intervention MeSH terms: Amphotericin B; Liposomal amphotericin B
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: central line fungal infections; antifungal lock therapy; Ambisome lock therapy