Inclusion Criteria:

1. Participants who are resident within the US.
2. Participants who are male or female, aged ≥18 years at the time of consent.
3. Participants must sign and provide informed consent.
4. Participants who experienced 1 or more Central-Line Associated Bloodstream Infections (CLABSI) within the previous 12 months.
5. Participants who have a permanent tunneled Central Venous Catheter (CVC) or permanent peripherally inserted central catheter (PICC) made of silicone or polyurethane, which has been in place for at least 7 days prior to enrollment.
6. Participants who require long term (\>6 months) Total Parenteral Nutrition (TPN) based on the investigator assessments.
7. Participants who require TPN for at least 3 days per week.
8. Participants who have a minimum of a 4-hour Catheter Lock Solution (CLS) dwelling time and are willing to lock all lumens at a minimum of every 7 days.
9. Participants who are clinically stable, in the opinion of the investigator, for at least 4 weeks prior to enrollment.
10. Participants who are able and willing to be trained or have a caregiver who is willing and able to be trained on the instillation, aspiration of DefenCath or heparin, and to maintain a daily diary.
11. Male or female participants:

1. Women of childbearing potential must have a negative pregnancy test at the screening visit (i.e., the participant is not pregnant); not be lactating; and use an acceptable method of contraception including but not limited to, abstinence, bilateral tubal ligation, vasectomized partner, a barrier method (diaphragm or condom), Depo-Provera, or hormonal contraceptive (oral, implant, ring, patch, IUD) for the duration of the program until at least 30 days after the last DefenCath CLS instillation. (NOTE: The participant must have used the chosen method of birth control for at least 1 month/cycle prior to enrollment into the study).
2. Male participants who are sexually active with a female partner of childbearing potential must agree to use male condoms with spermicide, even if the male participant has undergone a successful vasectomy (males with vasectomy can use condoms without spermicide), from Day 1 until at least 30 days after the last DefenCath CLS installation.

9. Participants who comply with all study procedures and follow-up evaluations.

Exclusion Criteria:

1. Any participant unable or not willing to sign inform consent.
2. Any participant who has received systemic antibiotic within the last 14 days. Topical antibiotics are permitted.
3. Any participant with visible evidence of compromised skin integrity present at the catheter exist site or catheter exit site infection.
4. Any participant with a temporary, non-tunneled CVC or temporary PICC.
5. Any participant that has received thrombolytic treatment (e.g., tissue-type plasminogen activator \[tPA\]-Cathflo), not as a part of the institution's standard of care for patency management, in current catheter within 30 days of randomization.
6. Any participant with known unstable arrhythmia, defined as presence of hemodynamic instability within a month prior to the baseline assessment.
7. Any participant using any type of antimicrobial-coated or heparin-coated catheter.
8. Any participant with documented chronic bleeding diathesis, active or recurrent bleeding within 1 month prior to randomization.
9. Any participant with a congenitally lethal condition or a life expectancy of less than 6 months.
10. Any participant with documented history of an atrial thrombus or known hypercoagulable state.
11. Any participant with an open, non-healing skin ulcer.
12. Any participant with current requirement for systemic immunosuppression that would increase risk of infection, including:

1. Steroid use at an equivalent dose of prednisone 20 mg/day anticipated or actual for at least 8 weeks.
2. Systemic chemotherapy
3. Methotrexate dose sufficiently high to suppress white blood cell count (WBC) below 5,000 cells/ul.
4. Azathioprine dose greater than 2.5 mg/kg/day
5. Calcineurin inhibitors

* i.Cyclosporine dose greater than 8 mg/kg
* ii.Tacrolimus dose greater than 0.4 mg/kg
6. Sirolimus dose greater 10 mg/daily
13. Any participant with known allergies or absolute contraindications to citrate, taurolidine, or heparin or a history of heparin-induced thrombocytopenia.
14. Any participant taking other medication with known systemic drug interaction with citrate, taurolidine or heparin.
15. Any participant anticipating receiving a transplant within 90 days. Participants can be on a transplant list but a participant with a known or anticipated transplant date within 90 days of study entry should be excluded from study participation. A participant who may receive a transplant \>90 days of study entry may remain on the study as long as they continue to receive TPN.
16. Any participant who is pregnant or lactating.
17. Any participant receiving continuous TPN (infusion over 24 hours).
18. Any participant with any medical conditions that render them unable to, or unlikely to complete the study or would interfere with optimal participation in the study or produce significant risk to participant.
19. Any participants who are participating in another interventional clinical study, except for non-pharmacological research studies.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 7/9/2025. Questions regarding updates should be directed to the study team contact.