Preemptive Ethanol Lock Therapy in Pediatric Bloodstream Infection

The study team will compare hospital length of stay (LOS) and attributable length of stay
(ALOS, the LOS attributable to CRI), in a randomized, un-blinded prospective trial utilizing
short-dwell ethanol-lock therapy (ELT) (4 hours to 24 hour dwell times per day, repeated for
up to 72 hours) placed within 24 - 36 hours of admission(Group 1, Preemptive ELT) versus ELT
placed at the time of first positive blood culture report (Group 2, Rescue ELT (Standard of
Care ).

ELT will be given in both groups, in combination with systemic antibiotics, for the treatment
of Catheter-related Infection (CRI) (suspected or proven) of the blood in children with
central catheters. Participants will be enrolled from patients with hematologic/oncologic
disorders and bone marrow or hematopoetic stem cell transplants admitted for care to
Children's Hospital of Michigan (CHM), a tertiary care pediatric hospital in Detroit,
Michigan. ALOS will be defined as the number of hospital days between first symptoms of CRI
(or date of admission for those admitted with symptoms) and first negative blood culture.

Aim 1: Compare two different treatment regimens for CRI using ELT (the preemptive ELT vs.
standard of care) by way of a prospective, randomized, two-arm study.

Study Hypothesis: The main hypothesis is that the short-dwell ethanol-lock therapy, defined
above, placed within 24 - 36 hours of symptoms/admission (Arm 1) versus ELT placement at the
time of first positive blood culture report (Arm 2), with concomitant systemic antibiotics,
for the treatment of CRI (suspected or proven) of the blood in children with central
catheters in the H/O/BMT population will have shorter hospital length of stay (LOS) and
attributable LOS (ALOS) and therefore lower hospital costs.

Aim 2: Compare sterilization rate of the infected intravascular device after ethanol-lock
therapy (as defined by a negative blood culture obtained from the infected catheter 24 - 72
hours after ELT) and central catheter salvage rate after CRI using ELT in the two study arms.
If the central catheter is salvaged for further clinical use, recurrence of infection with
the same organism (re-infection) of the central catheter for 28 days from date of first ELT
procedure will also be assessed.

Aim 3: Assess tolerability and adverse effects of the ELT (safety).

Aim 4: Perform sub-group analysis on the BSI episodes meeting National Healthcare Safety
Network (NHSN) criteria for laboratory confirmed central line associated BSI (CLABSI) into
the three categories of Criteria 1, 2 or 3 within the pediatric

Inclusion Criteria:

- All children up to 21 years of age, with central catheters (any type) that develop
symptoms and are admitted to CHM with an underlying H/O/BMT diagnosis for individual
episodes of suspected or proven CRI of the blood, including rule out sepsis, will be
screened for potential participation in this study.

- Individual CRI episodes in the same patient will be defined as a distinct central
catheter associated blood stream infection if separated by greater than 28 days from
prior ELT procedure and caused by a different organism identified on culture than the
prior central catheter associated blood stream infection episode.

- Participants meeting study enrollment criteria will be offered participation and must
have parental full informed consent, adolescent assent and young child verbal assent
prior to enrollment as applicable.

Exclusion Criteria:

- Children with documented allergy to ethanol or alcohol will be excluded. Blood
cultures from patients that are reported positive for pathogen growth within 12 hours
from the time they are obtained will be excluded from the study.

- Any patient at CHM with an infected central catheter and with another indwelling
foreign body that communicates directly with the bloodstream, of which infection or
colonization could not be excluded directly, will also be excluded from the study
(i.e. Left Ventricular Assist Device) as it will not be possible to assess
sterilization of the central catheter.

- Any patient with endocarditis or presumed endovascular infection will also be
excluded.

- Any patient deemed critically ill or unstable, upon admission or during the early
treatment course, in which case the treating clinician(s) feel that immediate line
removal is potentially life-saving will be excluded from the study.