Antimicrobial Catheter Lock Solution for the Treatment of Central Line Associated Bloodstream Infection (CLABSI)

Study Drug Administration (Lock Solution):

If you are found to be eligible to take part in this study, the infection will be treated
with antibiotics according to the standard of care. You will also receive the antimicrobial
catheter lock solution through the CVC 2 hours per day for at least 5 days within the first
week. In addition, you will receive the lock therapy for 2 additional days that could either
be given on the following next 2 days or within the next 2 weeks. After locking the catheter
for 2 hours, the HEAL lock will be cleared out, and the catheter will be flushed with normal
saline and then locked with heparin or normal saline until the next time it needs to be
used.

Study Visits:

On the first day after you receive the antimicrobial catheter lock solution, you will be
checked for side effects such as pain, burning, discomfort, drowsiness, headache, facial
redness, shortness of breath, and/or irregular heartbeat . After the last dose of receiving
the catheter lock solution, you will be asked if you have experienced any side effects after
receiving the catheter lock solution.

One (1) time each day while you are in the hospital, you will be checked for signs of
infection and your vital signs (heart rate, breathing rate, blood pressure, and temperature)
will be measured.

Every 2 days, blood (about 2 tablespoons) will be drawn to check for infection. This will
continue until the blood draws no longer show signs of infection.

Every week, blood (about one teaspoon) will be drawn to check that your liver is function
well.

Length of Study Participation:

You may receive the antimicrobial catheter lock solution for up to 7 days (over the course
of 3 weeks). You will no longer be able to receive it if intolerable side effects occur or
the infection does not go away after 7 days.

End of Treatment Visit:

- You will need to return to MD Anderson for your end of treatment visit within 7 days
(+/- 3 days) after your last dose of study drug.

- At this visit, you will be asked about any symptoms or illnesses that you may have had
since your last visit. You will be checked for signs of infection and your vital signs
will be measured.

- Blood (about 2 tablespoons) will be drawn to check for infection. You will be asked
about any antimicrobial drugs or therapies that you may be taking until the end of your
treatment.

Follow-Up Visit:

You will have a follow-up visit about 1 month after receiving the last dose of antimicrobial
catheter lock solution. At this visit, you will be checked for signs of infection and your
vital signs will be measured. If the doctor thinks it is needed, blood (about 2 tablespoons)
will be drawn to check for infection. You will be asked about any antimicrobial drugs that
you may be taking until the end of your treatment.

This is an investigational study. The study lock solution is made up of minocycline,
disodium ethylenediaminetetraacetate, and ethanol. Each of these are commercially available
and FDA approved for other uses:

- Minocycline - for the treatment of cellulitis, acne, respiratory and urinary tract
infections, gonococcal, chlamydial or ureaplasma urealyticum infections, cutaneous
nocardiosis, and syphilis.

- Disodium ethylenediaminetetraacetate - for the treatment of lead poisoning

- Ethanol - for cleaning your hands

It is investigational to give minocycline, disodium ethylenediaminetetraacetate, and ethanol
in combination as an antimicrobial lock solution.

Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients aged 18 years or older

2. Patients with indwelling CVC that have been in place for at least 14 days with
documented CLABSI as defined by CDC [62]. In neutropenic patients (defined as an
absolute neutrophil count (ANC) < 500 cells/mm3) with CLABSI, to confirm that CVC is
the source of the bacteremia, we will use the definitions of catheter-related
bloodstream infection (CRBSI) based on the mgmt guidelines of intravascular catheter
related infections published by IDSA [10]. This includes the evidence that points to
the CVC as the culprit: a) Paired quantitative blood cultures (QBC), whereby QBC are
drawn through the CVC and peripheral vein and the blood cultures from the CVC reveal
3-fold greater number of colonies than the peripherally drawn QBC. b) Differential
time to positivity, where blood cultures simultaneously drawn from the CVC and
peripheral vein are positive for the same organism, and the catheter-drawn blood
culture turns positive at least 2 hours earlier than the peripherally drawn blood
culture.

3. Female patients must be non-lactating and at no risk for pregnancy for one of the
following reasons: a) Postmenopausal for at least one year b) Post-hysterectomy
and/or post-bilateral ovariectomy and/or other surgical sterilization c) If of
childbearing potential, having a negative urine or serum human chorionic gonadotropin
(hCG) pregnancy test within 5 days prior to study enrollment and be using a highly
effective method of birth control throughout the course of the study. Reliable sexual
abstinence throughout the course of the study is acceptable as a highly effective
method of birth control for the purposes of this study.

4. Patients with short term non-tunneled catheters will be enrolled only if CVC cannot
be removed or exchanged (patient refuses to have CVC removed, CVC needed and no other
vascular access available, patient is thrombocytopenic (platelet count below 20,000)
that will prohibit inserting a new CVC at a different site).

Exclusion Criteria:

1. Patients allergic to tetracycline antibiotics or calcium EDTA

2. Patients on disulfiram or disulfiram like drugs

3. Patients with severe sepsis, septic shock, hypotension or who are considered
otherwise unstable

4. Presence of prosthetic valve

5. Presence of signs of metastatic deep-seated infection such as osteomyelitis or septic
pulmonary infarcts or endocarditis (as evidenced by vegetations on an
echocardiogram), or septic thrombosis

6. Patients with tunnel or catheter exit site infection or infusion port pocket abscess
as manifested by purulence at the exit site or inflammation with erythema or
induration of >1 cm in diameter.

7. Patients with Candida line infection

8. Patients who have been previously entered on the study