Antibiotic%20lock%20versus%20systemic%20antibiotics%20for%20catheter%20related%20infections%20in%20immunocompromised%20pediatric%20patients.

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)
• Selected studies
• Pediatric patients only
• Prophylaxis with ALT,
• Treatment with combined therapy (SAALT)
• 9 studies met above criteria!

13
Antibiotic-heparin lock solutions adults and
children

• Antimicrobial lock solutions
• Active ingredient
  Concentration (mg/ L)
• Vancomycin a
  0.02510
• Teicoplanin a
  0.0252.5
• Linezolid a
  0.22
• Amikacina,b
  110
• Gentamicin
  110
• Ciprofloxacin
  0.1252
• Ceftazidime
  0.52
• 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/ethylenediaminetet
  raacetate, 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

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?

17
References

• Chatzinikolaou I, Zipf TF, Hanna H, Umphrey J,
  Roberts WM, Sherertz R, Hachem R, Raad I.
  Minocycline-ethylenediaminetetraacetate lock
  solution for the prevention of implantable port
  infections in children with cancer. Clin Infect
  Dis. 2003 Jan 136(1)116-9. Epub 2002 Dec 11.
• Henrickson KJ, Axtell RA, Hoover SM, Kuhn SM,
  Pritchett J, Kehl SC, Klein JP. Prevention of
  central venous catheter-related infections and
  thrombotic events in immunocompromised children
  by the use of vancomycin/ciprofloxacin/heparin
  flush solution A randomized, multicenter,
  double-blind trial. J Clin Oncol. 2000
  Mar18(6)1269-78 .
• van de Wetering MD, van Woensel JB. Prophylactic
  antibiotics for preventing early central venous
  catheter Gram positive infections in oncology
  patients. Cochrane Database Syst Rev. 2007 Jan
  24(1)CD003295 .
• Fernandez-Hidalgo N, Almirante B, Calleja R, Ruiz
  I, Planes AM, Rodriguez D, Pigrau C, Pahissa A.
  Antibiotic-lock therapy for long-term
  intravascular catheter-related bacteraemia
  results of an open, non-comparative study. J
  Antimicrob Chemother. 2006 Jun57(6)1172-80.
  Epub 2006 Apr 5 .

18
References

• De Sio L, Jenkner A, Milano GM, Ilari I, Fidani
  P, Castellano A, Gareri R, Donfrancesco A.
  Antibiotic lock with vancomycin and urokinase can
  successfully treat colonized central venous
  catheters in pediatric cancer patients. Pediatr
  Infect Dis J. 2004 Oct23(10)963-5 .
• Bernardi M, Cavaliere M, Cesaro S. The
  antibiotic-lock therapy in oncoematology
  pediatric unit . Assist Inferm Ric. 2005
  Jul-Sep24(3)127-31.
• Viale P, Pagani L, Petrosillo N, Signorini L,
  Colombini P, Macri G, Cristini F, Gattuso G,
  Carosi G. Antibiotic lock-technique for the
  treatment of catheter-related bloodstream
  infections. J Chemother. 2003 Apr15(2)152-6.
• Gattuso G, Tomasoni D, Ceruti R, Scalzini A.
  Multiresistant Stenotrophomonas maltophilia
  tunneled CVC-related sepsis, treated with
  systemic and lock therapy. J Chemother. 2004
  Oct16(5)494-6 .
• Mermel LA, Farr BM, Sherertz RJ, Raad II, O'Grady
  N, Harris JS, Craven DE Infectious Diseases
  Society of America American College of Critical
  Care Medicine Society for Healthcare
  Epidemiology of America . Guidelines for the
  management of intravascular catheter-related
  infections Clin Infect Dis. 2001 May
  132(9)1249-72. Epub 2001 Apr 3 .

19
References

• Elwood RL, Spencer SE . Successful clearance of
  catheter-related bloodstream infection by
  antibiotic lock therapy using ampicillin. Ann
  Pharmacother. 2006 Feb40(2)347-50. Epub 2006
  Jan 31.
• Simon A, Bode U, Beutel K . Diagnosis and
  treatment of catheter-related infections in
  paediatric oncology an update. Clin Microbiol
  Infect. 2006 Jul12(7)606-20.
• Band JD. Pathogenesis of and risk factors for
  central venous catheter-related infections.
  Diagnosis of central venous catheter related
  bloodstream infections. Treatment of central
  venous catheter-related infections. www.
  uptodate. Com.
• Bagnall-Reeb H. Evidence for the use of the
  antibiotic lock technique. J Infus Nurs. 2004
  Mar-Apr27(2)118-22.
• Robinson JL, Tawfik G, Roth A . Barriers to
  antibiotic lock therapy in children with
  intravascular catheter-related bloodstream
  infections. Pediatr Infect Dis J. 2005
  Oct24(10)944 .