Central Line Fungal Infections Clinical Trial
Official title:
The Use of Antifungal Lock Therapy in Intestinal Failure and Other Patients
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.
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.
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