Antibiotic lock versus systemic antibiotics Antibiotic lock versus systemic antibiotics forfor catheter related infections in catheter related infections in

immunocompromised pediatric patients.immunocompromised pediatric patients.

Ewelina Mamcarz M.D., Ewelina Mamcarz M.D.,

Divya-Devi Joshi M.D.Divya-Devi Joshi M.D.

ObjectivesObjectives

Describe indications for systemic Describe indications for systemic antibiotics versus antibiotic lock therapyantibiotics versus antibiotic lock therapy

Evaluate type of antibiotic and treatment Evaluate type of antibiotic and treatment duration for antibiotic lock duration for antibiotic lock

Timing of the antibiotic lock: early/lateTiming of the antibiotic lock: early/late

Antibiotic lock as prevention of catheter Antibiotic lock as prevention of catheter associated bacteremiaassociated bacteremia

Background: Catheter related Background: Catheter related infectionsinfections

Leading cause of morbidity and mortality Leading cause of morbidity and mortality in critically ill hospitalized patientsin critically ill hospitalized patients

Organisms:Organisms:– Coagulase – negative staphylococciCoagulase – negative staphylococci– Staphylococcus aureusStaphylococcus aureus– Gram-negative bacteriaGram-negative bacteria– Candida ssp.Candida ssp.

Sources of infectionSources of infection

Colonization from the skinColonization from the skin

Intraluminal / hub contaminationIntraluminal / hub contamination

Hematologic seedingHematologic seeding

Clinical evaluation -CRIClinical evaluation -CRI

Local inflammationLocal inflammation

SepsisSepsis

Blood cultureBlood culture

Catheter dysfunctionCatheter dysfunction

Rapid improvement following catheter Rapid improvement following catheter removalremoval

TreatmentTreatment

Type of deviceType of device

Infecting pathogensInfecting pathogens

Presence of alternative venous access Presence of alternative venous access sitessites

Duration of anticipated need for accessDuration of anticipated need for access

TreatmentTreatment

Catheter removalCatheter removal

Systemic antibioticsSystemic antibiotics

Antibiotic lock therapy (ALT)- Antibiotic lock therapy (ALT)- little little evidence to support recommendationevidence to support recommendation

DataData

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

Antibiotic lockAntibiotic lock

First publication 1988-Messing et alFirst publication 1988-Messing et al

Higher concentration, longer duration of Higher concentration, longer duration of activity at the infected site without potential activity at the infected site without potential side-effects of systemic exposureside-effects of systemic exposure

Concentration and intra-luminal dwell Concentration and intra-luminal dwell time: lack of evidence based time: lack of evidence based recommendationsrecommendations

Lack of firm recommendations for Lack of firm recommendations for individual patientsindividual patients

ImmunocompromisedImmunocompromised population population

Pathogenesis of CRI complicatedPathogenesis of CRI complicated

Virulence of the pathogens variableVirulence of the pathogens variable

Host factors not well definedHost factors not well defined

Lack of diversity between studied Lack of diversity between studied populationspopulations

Absence of compelling clinical data to Absence of compelling clinical data to form recommendationsform recommendations

Data Data

Uncomplicated catheter-related Uncomplicated catheter-related bacteremias: bacteremias: Infectious Disease Society Infectious Disease Society of America – systemic antibiotics (7days) of America – systemic antibiotics (7days) +ALT (14 days)+ALT (14 days)

Local, systemic, extra-luminal CRI Local, systemic, extra-luminal CRI – –ALT should be combined with systemic ALT should be combined with systemic treatment for at least 72 hourstreatment for at least 72 hours

DataData

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

Antibiotic-heparin lock solutions: Antibiotic-heparin lock solutions: adults and childrenadults and children

Antimicrobial lock solutions Active ingredient Concentration (mg⁄ L)Vancomycin a 0.025–10Teicoplanin a 0.025–2.5Linezolid a 0.2–2Amikacina,b 1–10Gentamicin 1–10Ciprofloxacin 0.125–2Ceftazidime 0.5–2Amphotericin 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 hospitalpharmacy must be protected carefully against contamination with bacteria andfungi, and should be filter-sterilized and stored in a refrigerator.

Data: PreventionData: Prevention

3 studies: 3 studies: – prospective double blind study, prospective cohort prospective double blind study, prospective cohort

study, literature review (both children and adults)study, literature review (both children and adults)

Vancomycin/heparin/ciprofloxacin, Vancomycin/heparin/ciprofloxacin, vancomycin/heparin, vancomycin/heparin, minocycline/ethylenediaminetetraacetate, minocycline/ethylenediaminetetraacetate, vancomycin/teicoplaninvancomycin/teicoplaninResults: Results: Time to develop CRI longer with ALT,Time to develop CRI longer with ALT,

rate of total line infections decreased, no port rate of total line infections decreased, no port infections or thrombotic events were observed infections or thrombotic events were observed compared to ports flushed with heparin onlycompared to ports flushed with heparin only

Data: TreatmentData: Treatment

6 studies: 6 studies: – 2 case reports, 4 open pilot studies2 case reports, 4 open pilot studies

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

ALT Evidence based guidelinesALT Evidence based guidelines - -SignificanceSignificance

Decrease in mortality and morbidity Decrease in mortality and morbidity related to catheter related infectionsrelated to catheter related infections

Limit use of systemic antibioticLimit use of systemic antibiotic

Prevent resistance Prevent resistance

Improve quality of lifeImprove quality of life

Lack of serious complicationsLack of serious complications

Cost effective?Cost effective?

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