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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

Antibiotics in Acute Respiratory Failure

Robin J Green PhD

Division of Paediatric Pulmonology

University of Pretoria

definitions
Definitions
  • ALI- acute onset of impaired gas exchange PaO2/FIO2 <300
  • ARDS- PaO2/FIO2 <200
  • Oxygenation index=( MAP x FI02/Pao2)x100
acute lung injury
Acute Lung Injury
  • CAP
  • HIV-associated pneumonia
  • HAP/VAP
  • Viral lung disease
definition cap
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

causes cap
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

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

hiv infected children
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
pcp pneumonia
PCP Pneumonia
  • Diagnosis:

- Immune compromised

- Respiratory distress and few crepitations

- Interstitial pattern on CXR

- LDH > 500

- PCR

3 fluids in ards ali
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

managing severe pcp pneumonia
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
survival analysis adjusted age and hospital hazard ratio 0 54 95 ci 0 29 1 02 p value 0 06
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

cmv pneumonitis
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
hap definition
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
epidemiology
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
risk factors
Risk Factors
  • Immunodeficiency
  • Immunosuppression
  • Neuromuscular blockage
  • Septicaemia
  • TPN
  • Steroids
  • H2-blockers
  • Mechanical ventilation
  • Re-intubation
  • Transport while intubated
microbiology
Microbiology
  • Early-onset VAP:

- Strep pneumoniae

- Haemophilus influenzae

- Moraxella catarrhalis

  • Late-onset VAP (Resistant species):

- Staph aureus

- Pseudomonas aeruginosa

- Lactose fermenting gram-negatives

criteria for vap for infants younger than 12 months of age clinical criteria radiographic criteria
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

prevention strategies
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
management
Management
  • Antibiotic selection policies
  • De-escillation
  • Antibiotic rotation
  • Regular microbiology for a
  • Antibiotic STEWARDSHIP
dosage
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)

duration
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

de escillation
De-escillation
  • If broad spectrum antibiotics or combinations used downgrade with positive culture and sensitivity
  • Vancomycin can be used alone
  • Single antibiotics = combinations
decontaminate
Decontaminate
  • Hand washing – the most effective startegy to prevent resistance
  • All personnel and parents must hand wash
  • Anti-inflammatory strategies of Macrolides
slide27
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
antibiotics for esbl
Antibiotics for ESBL
  • Carbapenem
  • - Meropenem
  • - Imipenem
  • - Ertapenem (Invanz)
  • Cefepime (Maxipime)
  • Piperacillin/tazobactam (Tazocin)
  • Never – Ciprofloxacin/3rd Generation Cephalosporins
slide29

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

antibiotics for mrsa
Antibiotics for MRSA
  • Vancomycin (highly protein bound – better for septicaemia)
  • Linezolid (Zyvoxid) – better lung penetration
  • Teicoplanin
bronchiolitis in hiv positive children
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
summary
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%
aknowledgement
Aknowledgement
  • Dr RefiloeMasekela
  • Dr OmolemoKitchin
  • Dr TeshniMoodley
  • Dr Sam Risenga
  • Prof Max Klein