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Antibiotics in Acute Respiratory Failure

Antibiotics in Acute Respiratory Failure. Robin J Green PhD Division of Paediatric Pulmonology University of Pretoria. Definitions. ALI- acute onset of impaired gas exchange PaO 2 /FIO 2 <300 ARDS- PaO 2 /FIO 2 <200 Oxygenation index=( MAP x FI02/Pao2)x100. Acute Lung Injury. CAP

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Antibiotics in Acute Respiratory Failure

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  1. Antibiotics in Acute Respiratory Failure Robin J Green PhD Division of Paediatric Pulmonology University of Pretoria

  2. Definitions • ALI- acute onset of impaired gas exchange PaO2/FIO2 <300 • ARDS- PaO2/FIO2 <200 • Oxygenation index=( MAP x FI02/Pao2)x100

  3. Acute Lung Injury • CAP • HIV-associated pneumonia • HAP/VAP • Viral lung disease

  4. Definition CAP • Acute infection (less than 14 days) acquired in the community, of the lower respiratory tract, leading to cough or difficulty breathing, tachypnoea or chest-wall indrawing • Accounts for 30-40% of all hospital admissions • Case fatality rate 15-28% Zar HJ, et al SAMJ 2005

  5. Causes CAP • Bacterial: - Strep Pneumoniae - Haemophilus influenzae - Staph aureus - Moraxella catarrhalis • Atypical bacteria - Mycoplasma pneumoniae - Chlamydaphila pneumoniae/trachomatis • Viral - RSV - Human metapneumovirus - Parainfluenza - Adenovirus - Influenza - Rhinovirus - Measles virus

  6. Causes of CAP • In addition in HIV-infected children • Gram-negative bacteria • Staph aureus (including CA-MRSA) • TB • Fungi

  7. Organisms cultured - Ward

  8. Treatment CAP • Antibiotis for all – Amoxicillin (90mg/kg/day tds 5 days) – (IV Ampicillin) • < 2 months add aminoglycoside/cephalosporin • > 5 years add macrolide • HIV - infection add aminoglycoside • HIV - exposed < 6 months add cotrimoxazole • AIDS add cotrimoxazole Zar HJ, et al SAMJ 2005

  9. HIV-infected children • No evidence that PK/PD principles are different to healthy children • All specimens showed resistance to co-trimoxazole. • SavitreeChaloryooInternational Journal of PediatricOtorhinolaryngology 1998; 44:103-107 • Brink A. Personnel communication

  10. PCP Pneumonia • Diagnosis: - Immune compromised - Respiratory distress and few crepitations - Interstitial pattern on CXR - LDH > 500 - PCR

  11. 3. Fluids in ARDS/ALI NHLBI and ARDS net - FACTT trial • Conservative fluid management strategy favoured • Increase in ventilator free days and reduction in ICU stay, lower OI, plateau pressure, PEEP, higher PaO2/FIO2 • No increase rates of shock or renal failure • Need to closely monitor electrolytes Calfee CS, Matthay MA. Chest 2007;131:913-19

  12. Managing Severe PCP Pneumonia • Lung protective strategies (low tidal volume, high PEEP) • Fluid restriction • TMX/SMX • Oral steroids • Treating CMV pneumonitis – Ganciclovir • Early introduction HAART

  13. Survival analysis, adjusted age and hospitalHazard ratio 0.54, 95% CI(0.29-1.02), p value 0.06 Hazard ratio 0.54 95% CI(0.29-1.02) p value 0.06 Terblanche A, et al. SAMJ 2008

  14. CMV Pneumonitis • Diagnosis: - CMV viral load > 10 000 copies/ml - Blood • CMV PCR – NBBAL • Treatment: • Ganciclovir (10mg/kg/dose BD) • Duration – 3 weeks after starting HAART

  15. HAP Definition • HAP – Pneumonia developing more than 48 hours after admission to hospital • VAP – Nosocomial infection occuring in patients receiving mechanical ventilation that is not present at the time of intubation and develops more than 48 hours after initiation of ventilation

  16. Epidemiology • Pneumonia = 2nd 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

  17. Risk Factors • Immunodeficiency • Immunosuppression • Neuromuscular blockage • Septicaemia • TPN • Steroids • H2-blockers • Mechanical ventilation • Re-intubation • Transport while intubated

  18. Microbiology • Early-onset VAP: - Strep pneumoniae - Haemophilus influenzae - Moraxella catarrhalis • Late-onset VAP (Resistant species): - Staph aureus - Pseudomonas aeruginosa - Lactose fermenting gram-negatives

  19. Organisms cultured - PICU

  20. Criteria for VAP for Infants Younger than 12 Months of AgeClinical 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/mm3 or > 15,000/mm3 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 Wright ML, et al. Semin Pedaitr Infect Dis 2006;17:58-64

  21. Prevention Strategies • Head of bed elevation • Daily sedation holidays • Stress ulcer prophylaxis • DVT prophylaxis • Pneumococcal vaccination • Change in ventilator circuits only when dirty • Avoidance of re-intubation • Orotracheal intubation • Oropharyngeal toilet

  22. Management • Antibiotic selection policies • De-escillation • Antibiotic rotation • Regular microbiology for a • Antibiotic STEWARDSHIP

  23. Dosage • 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 or multiple dosings (3-4 hours for carbapenems)

  24. Duration • No culture = 3 – 5 days • Positive culture = 5-7 days. • Seldom need 10 days • Exceptions – Staph 2-3 weeks - PCP 3 weeks - Fungal 2-3 weeks

  25. De-escillation • If broad spectrum antibiotics or combinations used downgrade with positive culture and sensitivity • Vancomycin can be used alone • Single antibiotics = combinations

  26. Decontaminate • Hand washing – the most effective startegy to prevent resistance • All personnel and parents must hand wash • Anti-inflammatory strategies of Macrolides

  27. 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

  28. Antibiotics for ESBL • Carbapenem • - Meropenem • - Imipenem • - Ertapenem (Invanz) • Cefepime (Maxipime) • Piperacillin/tazobactam (Tazocin) • Never – Ciprofloxacin/3rd Generation Cephalosporins

  29. Risk factors for and outcomes of bloodstream infection caused by ESBL-producing Escherichia coli and Klebsiella species in childrenPaediatrics 2005;115: 942-949

  30. Antibiotics for MRSA • Vancomycin (highly protein bound – better for septicaemia) • Linezolid (Zyvoxid) – better lung penetration • Teicoplanin

  31. Bronchiolitis

  32. Viral Identification 2007

  33. Bronchiolitis in HIV positive children • 12% of bronchiolitics at PAH are HIV positive • Mean age 8 months old (vs 3 months in non HIV-infected children) • No increase in numbers co-infected in more mild disease

  34. Pearson correlation r = 0.138

  35. Pearson correlation r = 0.373

  36. Summary • CAP = Ampicillin +/- • HAP = Meropenem +/- • PCP = Bactrim + oral steroids + Ganciclovir • Bronchiolitis = nothing ? • Using this policy and noting that all HIV-infected children are offered ventilation if required – Mortality in PICU at PAH = 18.7%

  37. Aknowledgement • Dr RefiloeMasekela • Dr OmolemoKitchin • Dr TeshniMoodley • Dr Sam Risenga • Prof Max Klein

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