Antibiotics in Acute Respiratory Failure

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Antibiotics in Acute Respiratory Failure

• Robin J Green PhD
• Division of Paediatric Pulmonology
• University of Pretoria

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Definitions

• ALI- acute onset of impaired gas exchange
  PaO2/FIO2 lt300
• ARDS- PaO2/FIO2 lt200
• Oxygenation index( MAP x FI02/Pao2)x100

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Acute Lung Injury

• CAP
• HIV-associated pneumonia
• HAP/VAP
• Viral lung disease

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Definition Community Acquired Pneumonia

• 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
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Causes Community Acquired Pneumonia

• 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

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Causes of Community Acquired Pneumonia

• In addition in HIV-infected children
• Gram-negative bacteria
• Staph aureus (including Community Acquired-MRSA)
• TB
• Fungi

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Organisms cultured Paediatric Ward Pretoria
Academic Hospital
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Treatment Community Acquired Pneumonia

• Antibiotis for all Amoxicillin (90mg/kg/day tds
  5 days) (IV Ampicillin)
• lt 2 months add aminoglycoside/cephalosporin
• gt 5 years add macrolide
• HIV - infection add aminoglycoside
• HIV - exposed lt 6 months add cotrimoxazole
• AIDS add cotrimoxazole

Zar HJ, et al SAMJ 2005
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HIV-infected children

• No evidence that PK/PD principles are different
  to healthy children
• All specimens showed resistance to
  co-trimoxazole.
• Savitree Chaloryoo International Journal of
  Pediatric Otorhinolaryngology 1998 44103-107
• Brink A. Personnel communication

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PCP Pneumonia

• Diagnosis
• - Immune compromised
• - Respiratory distress and few crepitations
• - Interstitial pattern on CXR
• - LDH gt 500
• - PCR

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3. Fluids in Acute Respiratory Distress
Syndrome/Acute Lung Injury

• 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
  2007131913-19

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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

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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
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CMV Pneumonitis

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

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Hospital Acquired Pneumonia
Definition

• HAP Pneumonia developing more than
  48 hours after admission to
  hospital
• Ventilator Associated Pneumonia 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

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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

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Risk Factors

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

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Microbiology

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

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Organisms cultured PICU Pretoria Academic
Hospital
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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 lt4,000/mm3 or gt 15,000/mm3
  and band forms gt 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 lt100 beats/min or gt170 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 gt48 hours after initiation of mechanical
  ventilation

Wright ML, et al. Semin Pedaitr Infect Dis
20061758-64
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VAP - 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

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Management

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

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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)

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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

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De-escillation

• If broad spectrum antibiotics or combinations
  used downgrade with positive culture and
  sensitivity
• Vancomycin can be used alone
• Single antibiotics are usually equivalent to
  combinations

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Decontaminate

• Hand washing the most effective startegy to
  prevent resistance
• All personnel and parents must hand wash
• Anti-inflammatory strategies of Macrolides this
  strategy holds promise for the future

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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

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Antibiotics for Extended Spectrum Beta-Lactamase
producers

• Carbapenem
• - Meropenem
• - Imipenem
• - Ertapenem (Invanz)
• Cefepime (Maxipime) in some cases
• Piperacillin/tazobactam (Tazocin)
• Never Ciprofloxacin/3rd Generation
  Cephalosporins

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Risk factors for and outcomes of bloodstream
infection caused by ESBL-producing Escherichia
coli and Klebsiella species in childrenPaediatric
s 2005115 942-949
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Antibiotics for MRSA

• Vancomycin (highly protein bound better for
  septicaemia)
• Linezolid (Zyvoxid) better lung penetration
• Teicoplanin

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Bronchiolitis
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Viral Identification 2007 Pretoria Academic
Hospital
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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

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Pearson correlation r 0.138
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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

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Aknowledgement

• Dr Refiloe Masekela
• Dr Omolemo Kitchin
• Dr Teshni Moodley
• Dr Sam Risenga
• Prof Max Klein