Antifungal therapy accompanied by prompt removal of the catheter is the current standard of care for central venous catheters (CVC) Candida sp. infections.1,2 Patients who require long-term total parenteral nutrition or who have limited access represent difficult management issues.3
Removal of infected CVC catheters may reduce the rate of Candida-associated complications; literature reviews question whether the outcomes of removal substantiate this being the standard of care.4 CVC salvage rates are very low in patients with candidemia who are treated with systemic antifungals alone.1 Castagnola et al5 have reported success in treating a Candida parapsilosis Broviac (C. R. Bard, Inc., Murray Hill, NJ) catheter-related fungemia in an infant requiring total parenteral nutrition. The novel approach used consisted of an antifungal lock solution for 8 hours a day with concomitant systemic antifungal administration. Previous reports demonstrating an effect of antifungal lock therapy have used dwell-times of 12 hours or more.6 The decreased lock-time used by Castagnola et al5 allowed the CVC to continue being used in patients in whom a long-term lock is not feasible. This same approach was also found to be successful in a rabbit model report using the lock only 8 hours a day.7
We report our experience of 4 patients, one of whom underwent lock therapy 3 separate times, with CVC Candida infections using liposomal amphotericin-B lock therapy based on the aforementioned report.
A 17-month-old girl with a history of megacystic microcolon intestinal hypoperistalsis syndrome was admitted to a children's hospital with fever and possible sepsis. The child had a Broviac catheter, the second such catheter placed for parenteral nutrition. Her first Broviac was removed 4 months before this admission because of a fungal infection that could not be cleared with systemic antifungal agents. A blood culture drawn on the day of admission was positive for Candida glabrata. Initially, the child was started on intravenous fluconazole 12 mg/kg/day given once a day. She had blood cultures drawn daily for the next 14 days. Over the first 5 days, daily blood cultures remained positive. On the fifth day, her antifungal regimen was changed to systemic liposomal amphotericin-B 5 mg/kg/d. The following day, liposomal amphotericin-B lock-therapy was begun while continuing the daily systemic liposomal amphotericin-B. The lock used a portion of a 3 mL solution of 8 mg of liposomal amphotericin-B and 5% dextrose with 200 units of heparin and placed in the line for 8 hours a day for 7 days. The blood cultures that were drawn on the day after the liposomal amphotericin-B lock was started were negative and remained negative for the rest of the child's hospitalization. After the 7 days of liposomal amphotericin-B lock and 8 days of systemic liposomal amphotericin-B, the patient was restarted on fluconazole and remained on this medication for a total antifungal regimen of 28 days from admission. Follow-up blood cultures over the next 4 months remained sterile.
The same patient presented 5 months later and cultures taken from the catheter at the time of admission grew C. albicans and C. glabrata. She was treated with the lock therapy using the aforementioned technique and systemic liposomal amphotericin-B for 10 days. The infection did not resolve, and due to the patient's clinical status, the catheter was removed. A new Broviac was placed 1 week later.
The same child presented again 3 months later with an infection involving the new CVC, this time yielding C. glabrata alone. She was treated both systemically and with the lock therapy with liposomal amphotericin-B for 16 days. Her cultures were negative after 6 days of the treatment. Subsequent cultures were sterile (Table 1).
A 7-year-old girl with fetal alcohol syndrome and familial polyposis, who was status-post bowel resection leading to short bowel syndrome, was admitted to the children's hospital with fever and emesis. She was using her second Broviac. Her first Broviac had been removed because of a bacterial infection that could not be cleared. She had a long-standing history of Gram-negative bacilli catheter-related infections, but no history of fungal catheter-related infections. Her current Broviac was placed 1 year before this admission and was used to provide parenteral nutrition. She had been receiving gentamicin for 5 days before admission for a Serratia marcescens infection in her Broviac line. On the day of admission, the patient had a positive blood culture for Candida albicans. She completed a 10-day course of gentamicin for her S. marcescens. She was also treated with systemic liposomal amphotericin-B 5 mg/kg/d. She had blood cultures drawn for the next 2 days, which remained positive for C. albicans. The day after admission, we started liposomal amphotericin-B lock therapy, while continuing parenteral therapy as well. She did not have cultures drawn from the third day of lock therapy until the sixth day of lock therapy. The culture drawn on the sixth day of lock therapy was negative and cultures drawn every other day for the next 14 days remained sterile. The lock therapy was used for 17 days. The systemic therapy was continued for 21 days. Follow-up blood cultures remained sterile.
A 6-month-old boy with jejunal atresia, status post-bowel resection resulting in short gut syndrome, was admitted to the children's hospital with increased fussiness and irritability. The patient was already using his third Broviac. The first 2 catheters had been removed because of fungal infections that could not be cleared with systemic antifungal agents. His current Broviac had been in place for 2 months before admission. Cultures from his current catheter at admission yielded C. parapsilosis. Treatment was comprised of liposomal amphotericin-B lock therapy and systemic liposomal amphotericin-B. The patient had negative cultures for 8 days after initiating lock therapy. The patient continued 7 additional days of lock therapy and systemic liposomal amphotericin-B before discharge. However, the patient returned 6 days later and C. parapsilosis was once again cultured from his Broviac catheter. The CVC was removed because of the patient's clinical status and replaced at a later date.
A 1-year-old Hispanic girl with congenital nephrotic syndrome presented to the children's hospital with a Broviac catheter infection from an outside hospital. Cultures revealed the organism to be C. guilliermondii. Treatment was comprised of liposomal amphotericin-B lock therapy and systemic liposomal amphotericin-B for 14 days. Serial cultures were negative after day 3 of treatment. Subsequent cultures revealed no fungal growth throughout the remainder of the patient's hospital course.
Treatment of CVC fungal infections has traditionally comprised catheter removal with or without systemic antifungal treatment. The liposomal amphotericin-B lock approach allows the clinician some potential advantages compared with systemic therapy alone. A higher concentration of medicine can be delivered to the lumen of the catheter.8 We recommend this approach not be used in hemodynamically unstable patients or patients with evidence of end-organ involvement until further studies are concluded. This treatment could also help decrease the expense and complications associated with removal and replacement of CVCs. A key point that needs to be addressed is the appropriate length of treatment with liposomal amphotericin-B lock therapy. As patient 3 demonstrated, we were able to suppress the infection temporarily, but the patient returned 6 days later with the same species of Candida. We suggest that a controlled trial of the liposomal amphotericin-B lock therapy or other antifungal lock therapies be conducted as an alternative to removal of CVC in patients with fungal blood infection.
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2. Pappas PG, Rex JH, Sobel JD, et al. Guidelines for the treatment of candidiasis. Clin Infect Dis
3. O'Grady NP, Alexander M, Dellinger EP, et al. Guidelines for the prevention of intravascular catheter-related infections. Pediatrics
4. Nucci M, Anaissie E. Should vascular catheters be removed from all patients with candidemia? An evidence based review. Clin Infect Dis
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6. Viale P, Petrosillo N, Signorini L, Puoti M, Carosi G. Should lock therapy always be avoided for central venous catheter-associated fungal bloodstream infections? Clin Infect Dis
7. Schinabeck MK, Long LA, Hossain MA, et al. Rabbit model of Candida albicans
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8. Johnson DC, Johnson FL, Goldman S. Preliminary results treating persistent central venous catheter infections with the antibiotic lock technique in pediatric patients. Pediatr Infect Dis J