Striking The Balance. Risk Factors for Late Onset Infections Nosocomial. Risk Factors 6/15/2012

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1 . Is It An Infection??. Robin J Green MBBCh, DCH, FC Paed, DTM&H, MMed, FCCP, PhD, Dip Allergy, FAAAAI, FRCP Department of Paediatrics and Child Health Striking The Balance Overuse of Antibiotics: - Resistance - Side effects - Co-lateral damage -Cost Underuse of Antibiotics: - Increased mortality (10-30% for early onset sepsis) - Morbidity (prolonged stay) -Cost 1 2 Decide Do I need an antibiotic (Appropriate and Optimal Use) Some reasons not to use antibiotics: -No risk of sepsis -Neonate not ill - Inflammatory markers are negative What if the antibiotic isn t working: - Think again may not be an infection - Think again may be an abscess/pus Routine Antibiotics for all Preterm Neonates Have NO Role Clinical sepsis: - Intervention = 31.9% - Control = 25.4% (P=0.392) Mortality was equivalent in both groups The incidence of NEC and the duration of hospital stay were comparable in both groups Conclusion: In low risk preterm neonates we found no evidence that routine antibiotic use has a protective effect Tagare A, et al. J Hosp Infect 2010;74: Risk Factors Prolonged rupture membranes (>18 hours) Foetal distress Chorio-amnionitis Maternal fever Multiple obstetric procedures Extreme Prematurity? Suspected GBS (previous pregnancy, maternal culture) Risk Factors for Late Onset Infections Nosocomial Previous antibiotic use Inappropriate antibiotic use (especially Cepahalosporins) Length of stay Intubation Catheterisation Lack of enteral feeding Cipolla D, et al. J Matern Fetal Neonatal Med 2011;24:23-6 Deng C, et al. Pediatr Int 2011;53:

2 Microbiology Early-onset Sepsis: - E coli - Group B strep. (most important Day 1) Late-onset Sepsis: - Coagulase negative Staph. - Staph. aureus - Gram-negatives (esp MDR) - Fungal (esp VLBW) Preventing Nosocomial Sepsis Change intravenous lines < 21 days (Chathas MK, et al. Am J Dis Child 1990;144: ) Remove lines when cultured organism (Benjamin Jr DK, et al. Pediatrics 2001;107: ) NICU design (37-55 m per bed, sinks within 6 m each bed, equipment for each bed) (Clark R, et al. J Perinatol 2004;24: ) Vancomycin prophylaxis for central lines Guarded (Craft AP, et al. Cochrane Database Syst Rev 2000;2:CD001971) Careful antibiotic stewardship and policies (De Man P, et al. lancet 2000;355:973-8) 8 Prevention that Doesn t Work Prophylactic antibiotics No evidence (Austin N, et al. Cochrane Database Syst Rev 2009;7:CD003478) Surface coated enteral catheters No evidence in neonates Frequency endotracheal suctioning (4 vs 8 hrly) No difference (Cordero L, et al. J Perinatol 2000;20:151-6) Closed vs open tracheal suctioning - No effect (Deppe SA, et al. Crit Care Med 1990;18: ) Prevention that Doesn t Work Gowning before entering NICU No evidence (Donowitz LG. Pediatrics 1986;77:35-8 Tan SG, et al. Int J Nurs Pract 1995;1:52-8 Pelke S, et al. Arch paediatr Adolesc Med 1994;148: ) Intravenous FFP No effect (Acunas BA, et al. Arch Dis Child Fetal Neonatal Ed 1994;70:182-7) Skin protection with emolients - Harmful (Campbe ll JR, et al. Pedaitrics 2000;105: ) 9 10 Management Biomarkers ANTIBIOTICS Have a Policy/Guideline Know your Bugs Try for Stewardship CRP PCT WCC 2

3 Duration No culture + normal CRP* + well baby = 48 hours No culture + abnormal CRP* + unwell baby = 5 days No culture + abnormal normal CRP + unwell well baby = 48 hours after CRP normal/baby gets well Positive culture: GBS = 10 days (14 days CSF) -Gram negative = 10 days (21 days CSF) -Staph aureus = 2-3 weeks - Fungal = 2-3 weeks (after negative culture) Sensitivity 78% Al-Zwaini EJ. East Mediterr Health J 2009;15: Antibiotics for ESBL (lactose fermenters) Carbapenem -Ertapenem (Invanz) -Meropenem -Imipenem Cefepime (Maxipime) + Clavulanate Piperacillin/tazobactam Never Ciprofloxacin/Rocephin All of these induce co-lateral damage Antibiotics for MRSA Vancomycin Concerns:»Unfavourable PK/PD Dose close to MIC»Highly plasma protein bound poor lung penetration unsuitable for HAP»Adverse events kidney/ear/histamine release (anaphylaxis) Linezolid (Zyvoxid) Teicoplanin Neurodevelopmental Outcomes and Bloodstream Infections in Infants,1000 g 57% P < vs no infection Prophylactic Use Antifungals for Invasive Fungal Infection in VLBW Neonates Oral antifungal prophylaxis studies: - Under-powered - Quasi-randomization -Lack of blinding Meta-analyis found RR 0.19 ( ) invasive fungal infections No effect on mortality Diflucan (fluconazole)* A maintenance dose of at least 12 mg/kg day! is needed (in the first 90 days after birth) to achieve an AUC / MIC of >50 for Candida spp with an MIC of <8 µg/ml From PD point of view, recommended treatment dose is too low! May result in mycological failure! Is this a reason for the exhorbitant mortality rate of candida septicaemia in neonates (+/-22%)? Austin N, et al. Cochrane Database SystRev 2009;7:CD * Data for orginal 3

4 Organisms That Tell You Something And That Something Isn t Good Candida parapsolosis Acenitobacter baumanii Vancomycin resistant Enterococci NosocomialSepsis Prevention Strategies Physician willingness Antibiotic protocols Hand washing Sterile precautions Adequate Finances Patient spacing When Money is Short Doctors Need to Go The Extra Mile Epidemiology Physician willingness Antibiotic protocols Hand washing Sterile precautions Patient spacing Inadequate Finances Pneumonia = 2 nd most common nosocomial infection Accounts for 18 26% of nosocomial infections Children aged 2 12 months most affected 95% of nosocomial pneumonia occurs in ventilated children 21 Risk Factors for VAP Immunodeficiency Immunosuppression Neuromuscular blockage Septicaemia TPN Steroids H2-blockers Mechanical ventilation Re-intubation Transport while intubated Microbiology Early-onset HAP: - Strep pneumoniae - Haemophilus influenzae - Moraxella catarrhalis Late-onset HAP: -Staph aureus -MRSA - Pseudomonas aeruginosa/acenitobacter - MDR -Gram-negative Enterobacteriaceae -ESBL Often more resistant organisms 4

5 Criteria for VAP for Infants Younger than 12 Months of Age Clinical Criteria / Radiographic Criteria Worsening gas exchange with at least 3 of the clinical criteria: Temperature instability without other recognized cause White blood cells <4,000/mm 3 or > 15,000/mm 3 and band forms > 10% New onset purulent sputum or change in the character of sputum or increased respiratory secretions Apnea, tachypnea, increased work of breathing, or grunting Wheezing, rales, or rhonchi Cough Heart rate <100 beats/min or >170 beats/min plus radiographic criteria At least 2 serial chest x-rays with new or progressive and persistent infiltrate, consolidate, cavitation or pneumatocele that develops >48 hours after initiation of mechanical ventilation Prevention Strategies Infection control Head of bed elevation Daily sedation holidays Stress ulcer prophylaxis DVT prophylaxis In-line suctioning Oropharyngeal toilet Orotracheal intubation Change in ventilator circuits only when dirty Avoidance of re-intubation Wright ML, et al. Semin Pedaitr Infect Dis 2006;17:58-64 Biomarkers CRP + PCT may be useful to: - Document HAP/VAP - Determine bacterial aetiology - Determine duration of antibiotics Management ANTIBIOTICS Antibiotic selection policies Antibiotic rotation? Regular microbiology for a Antibiotic Stewardship: designed to optimize antimicrobial therapy administered to hospitalized patients, to ensure cost-effective therapy, improve patients' outcome while containing bacterial resistance. Selecting Antibiotics Dosage Mode of killing Concentration AUC/MI C Time Above MIC PK/PD Adverse events Intervene early and appropriately Consider antibiotic for relevant organisms Consider dosage interval and total dose depending on the antibiotic mode of killing PK = Effect of body on drug (absorption, availability, metabolism, excretion) PD = Effect of drug on body (receptor binding, tissue penetration) 5

6 PK = Dosage + Concentration Correct antibiotic dosages and duration Correct antibiotic administration -Concentration dependent antibiotics (Aminoglycosides, quinolones) = single daily concentration -Time dependent antibiotics (B-lactams, vancomycin, pip-taz, carbapenems, linezolid) = continuous infusion over 24 hours (3-4 hours for carbapenems, TDS for linezolid) Duration No culture = 3 days URTI = 3-5 days Positive culture = 5-7 days (including tonsillitis, sinusitis) or 3-5 days after clinical improvement Seldom need 10 days Exceptions Staph 2-3 weeks -PCP 3 weeks -Fungal 2-3 weeks Decontaminate Hand washing the most effective strategy to prevent resistance All personal and parents must hand wash Use notices and wall mounted sprays Anti-inflammatory strategies of Macrolides/Linezolid Dont Use third generation cephalosporins routinely (except meningitis) Use inappropriate antibiotics Use a long course Use too low a dose Routinely combine antibiotics Routinely use probiotics Why Linezolid is Best for MRSA MIC break point = 4mg/L Excellent lung penetration Quorum sensing ability = Anti-inflammatory effects Favourable safety profile Percentage of Bacteria at each MIC value (mg/l) (n=40) Antibiotic Linezolid Teicoplanin Vancomycin Kuti JL, et al. Clin Microbiol Infect 2008;14:

7 Antibiotic Stewardship A multidisciplinary team including at least an infectious disease physician and a clinical pharmacist is required. Feedback to the provider, education and antimicrobial restriction Antibiotic Stewardship Elements Treat only bacterial infections Do not treat colonisation Review antibiotics at 48 hours Prevent the chain of spread Infection control Select antibiotics carefully PK/PD Surveillance/audit Interact with the microbiologist Adequate staffing Eliminate non-essential tracheal suctioning Antibiotic Stewardship Definition Wise use of antibiotics to improve patient outcomes and minimise resistance and adverse outcomes Touch Don t touch the patient without washing hands Pause Pause before touching the next patient Engage Don t engage with the patients crib Conclusion Do I need an antibiotic? Select the most appropriate antibiotic Use the correct dose and interval Short courses are better Avoid 3 rd generation cephalosporins Antibiotic Protocols Antibiotic Stewardship WASH YOUR HANDS 42 7