Antibiotics in Acute Antibiotics in Acute Respiratory FailureRespiratory Failure

Robin J Green PhDRobin J Green PhD

Division of Paediatric PulmonologyDivision of Paediatric Pulmonology

University of PretoriaUniversity of Pretoria

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

• CAP

• HIV-associated pneumonia

• HAP/VAP

• Viral lung disease

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

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

Causes of Community Acquired Pneumonia

• In addition in HIV-infected children

• Gram-negative bacteria

• Staph aureus (including Community Acquired-MRSA)

• TB

• Fungi

Organisms cultured – Paediatric Ward Organisms cultured – Paediatric Ward – Pretoria Academic Hospital– Pretoria Academic Hospital

0

1

3 3

2

5 27

4

0 10 20 30 40 50

Pneumonia

Meningitis

Pneumococcus ESBL Klebs E. Coli MRSA Staph aureus CNS Alpha Haem. Strep Salmonella t. None N. Meningitis

Treatment Community Acquired Pneumonia

• 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 childrenHIV-infected children

• No evidence that PK/PD principles are different No evidence that PK/PD principles are different to healthy childrento healthy children

• All specimens showed resistance to co-All specimens showed resistance to co-trimoxazole.trimoxazole.

• Savitree Chaloryoo Savitree Chaloryoo International Journal of Pediatric Otorhinolaryngology 1998; 44:1998; 44:103-107 103-107

• Brink A. Personnel communicationBrink A. Personnel communication

PCP Pneumonia

• Diagnosis:

- Immune compromised

- Respiratory distress and few crepitations

- Interstitial pattern on CXR

- LDH > 500

- PCR

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

NHLBI and ARDS net - FACTT trialConservative fluid management strategy

favouredIncrease in ventilator free days and reduction in

ICU stay, lower OI, plateau pressure, PEEP, higher PaO2/FIO2

No increase rates of shock or renal failureNeed to closely monitor electrolytes Calfee CS, Matthay MA. Chest 2007;131:913-19

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 hospitalHazard ratio 0.54, 95% CI(0.29-1.02), p value 0.06

.4.6

.81

Sur

viva

l

0 20 40 60 80analysis time

Placebo Prednisone

Cox proportional hazards regression

Hazard ratio 0.5495% CI(0.29-1.02)

p value 0.06

Terblanche A, et al. SAMJ 2008

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

Hospital Acquired Pneumonia Definition

1. HAP – Pneumonia developing more than 48 hours after admission to hospital

2. 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

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

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

Microbiology

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

Organisms cultured – PICU Organisms cultured – PICU Pretoria Academic HospitalPretoria Academic Hospital

0

0

3

0

11

0 5 10 15 20

Pneumonia

Meningitis

Pneumococcus ESBL Klebs MRSA CNS Gram positive cocci SternotrophomonasNon haem strep Bacillus spNone N. Meningitis

Criteria for VAP for Infants Younger than 12 Months of Age

Clinical Criteria / Radiographic CriteriaWorsening 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

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

Management

• Antibiotic selection policies

• De-escillation

• Antibiotic rotation

• Regular microbiology for a

• Antibiotic STEWARDSHIP

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

• 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

• 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

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

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 Extended Spectrum Beta-Lactamase producers

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

Cephalosporins

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

• Vancomycin (highly protein bound – better for septicaemia)

• Linezolid (Zyvoxid) – better lung penetration

• Teicoplanin

Bronchiolitis

Viral Identification 2007 – Pretoria Academic Hospital

0

2

4

6

8

10

12

14

Jan March May July

RSV

Para'flu

'Flu

Adeno

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

CRP vs WCC

0

5

10

15

20

25

30

0 50 100 150 200 250

CRP

WC

C

Pearson correlation r = 0.138

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%

AknowledgementAknowledgement

• Dr Refiloe MasekelaDr Refiloe Masekela

• Dr Omolemo KitchinDr Omolemo Kitchin

• Dr Teshni MoodleyDr Teshni Moodley

• Dr Sam RisengaDr Sam Risenga

• Prof Max KleinProf Max Klein