1. Antibiotic lock versus systemic antibiotics for catheter related infections in immunocompromised pediatric patients. Ewelina Mamcarz M.D., Divya-Devi Joshi M.D.

2. Objectives Describe indications for systemic antibiotics versus antibiotic lock therapy Evaluate type of antibiotic and treatment duration for antibiotic lock Timing of the antibiotic lock: early/late Antibiotic lock as prevention of catheter associated bacteremia

3. Background: Catheter related infections Leading cause of morbidity and mortality in critically ill hospitalized patients Organisms: –Coagulase – negative staphylococci –Staphylococcus aureus –Gram-negative bacteria –Candida ssp.

4. Sources of infection Colonization from the skin Intraluminal / hub contamination Hematologic seeding

5. Clinical evaluation -CRI Local inflammation Sepsis Blood culture Catheter dysfunction Rapid improvement following catheter removal

6. Treatment Type of device Infecting pathogens Presence of alternative venous access sites Duration of anticipated need for access

7. Treatment Catheter removal Systemic antibiotics Antibiotic lock therapy (ALT)- little evidence to support recommendation

8. Data Guidelines from the Infectious Diseases Society of America (IDSA): CRI documented, pathogen identified-narrow spectrum systemic abx and consider ALT Onder at al: timing of antbc locks: ALT more effective early in therapy, diminished need for catheter removal Pervez at al: ALT for prevention of CRI: decreased incidence of CRI, improved survival of catheters

9. Antibiotic lock First publication 1988-Messing et al Higher concentration, longer duration of activity at the infected site without potential side-effects of systemic exposure Concentration and intra-luminal dwell time: lack of evidence based recommendations

10. Lack of firm recommendations for individual patients Immunocompromised population Pathogenesis of CRI complicated Virulence of the pathogens variable Host factors not well defined Lack of diversity between studied populations Absence of compelling clinical data to form recommendations

11. Data Uncomplicated catheter-related bacteremias: Infectious Disease Society of America – systemic antibiotics (7days) +ALT (14 days) Local, systemic, extra-luminal CRI – ALT should be combined with systemic treatment for at least 72 hours

12. Data Search strategy: Pub Med (1990-2008) Pub Med (1990-2008) Selected studies: Selected studies: Pediatric patients only Pediatric patients only Prophylaxis with ALT, Prophylaxis with ALT, Treatment with combined therapy (SA+ALT) Treatment with combined therapy (SA+ALT) 9 studies met above criteria!

13. Antibiotic-heparin lock solutions: adults and children Antimicrobial lock solutions Active ingredient Concentration (mg⁄ L) Vancomycin a 0.025–10 Teicoplanin a 0.025–2.5 Linezolid a 0.2–2 Amikacina,b 1–10 Gentamicin 1–10 Ciprofloxacin 0.125–2 Ceftazidime 0.5–2 Amphotericin B desoxycholate 2 (in glucose 5% w⁄ v) A: Stable for ‡ 24 h without loss of efficacy when combined with heparin 100 U⁄ mL. B: Vancomyin 25 mg ⁄ L + amikacin 25 mg⁄ L + heparin 100 000 U⁄ L in NaCl 0.9% Note: Standard antibiotic lock technique ampoules prepared by the hospital pharmacy must be protected carefully against contamination with bacteria and fungi, and should be filter-sterilized and stored in a refrigerator.

14. Data: Prevention 3 studies: –prospective double blind study, prospective cohort study, literature review (both children and adults) Vancomycin/heparin/ciprofloxacin, vancomycin/heparin, minocycline/ethylenediaminetetraacetate, vancomycin/teicoplanin Results: Time to develop CRI longer with ALT, rate of total line infections decreased, no port infections or thrombotic events were observed compared to ports flushed with heparin only rate of total line infections decreased, no port infections or thrombotic events were observed compared to ports flushed with heparin only

15. Data: Treatment 6 studies: –2 case reports, 4 open pilot studies Vancomycin/heparin, ciprofloxacin/heparin, amikacin/heparin, urokinase /vancomycin, ampicilin alone+ systemic antibiotics 168 episodes of CRI: 143 (85%) episodes cured (negative bld cx – mean: 4days-1month),10 catheter removals, median catheter follow up -96 days,168 days (1 study),25 (15%) episodes of therapeutic failure (recurrence of febrile bacteremia),1 death.

16. ALT Evidence based guidelines - Significance Decrease in mortality and morbidity related to catheter related infections Limit use of systemic antibiotic Prevent resistance Improve quality of life Lack of serious complications Cost effective?

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