Silverstein and Hopper Chapter 40: Ventilator-Associated Pneumonia

Ventilator-Associated Pneumonia (VAP)

Pneumonia that arises more than 48 hours after endotracheal intubation and mechanical ventilation that was not present at the time of intubation

What % of mechanically ventilated human patients does VAP occur in?

3-10%

Risk of Developing VAP and the Duration of Ventilation

• Risk of developing VAP varies with duration of ventilation

• Most animals receive mechanical ventilation for less than a week so the majority of cases of VAP would be expected to occur in the first few days of ventilation but the cumulative incidence will increase as the number of days of intubation increases

• Development of VAP increases the length of time mechanical ventilation is necessary

What are the potential outcomes once a pathogen gets past the cuff of the endotracheal tube?

• Pathogen may be cleared by normal respiratory defenses

• The lower airways may be colonized

• The tracheobronchial tree may become infected (ventilator-associated tracheobronchitis [VAT]), or if the pulmonary parenchyma becomes infected, VAP occurs

Normal Respiratory Defenses to Colonization or Infection of the Lower Airways

• Cough

• Mucus clearance

• Humoral and cellular immune responses

How are normal respiratory defenses compromised in an anesthetized critically ill animal?

• Reduced ability to cough due to sedation and presence of endotracheal tube

• Inflation of a cuffed endotracheal tube depresses mucociliary clearance rate

• Critical illness is associated with decreased immune system function and increased susceptibility to nosocomial infection

• Evidence for neutrophil dysfunction in VAP with a reduced phagocytic capability and elevation in neutrophil proteases in the alveolar space

What is a prime risk factor for development of VAP?

• Prime risk factor for development of VAP is the presence of an endotracheal tube

  • The risk for the development of VAP in patients receiving noninvasive mechanical ventilation is lower than in patients with endotracheal intubation

What are the two major pathologic mechanisms behind VAP?

Microaspiration past the cuff of the endotracheal tube

Biofilm development within the endotracheal tube

Pathologic Mechanisms Behind VAP - Microaspiration Past the Cuff of the Endotracheal Tube

• Inflation of the endotracheal cuff allows for pooling of secretions beyond the vocal folds but above the cuff

• When high-volume, low-pressure cuffs are used to prevent tracheal injury, the longitudinal folds that develop are associated with microaspiration or macroaspiration of subepiglottic fluid with subsequent translocation of bacterial to the interior of the endotracheal tube or airways

Pathologic Mechanisms Behind VAP - Biofilm Development within the Endotracheal Tube

• Once bacteria are present on the internal surface of the endotracheal tube, these bacteria may easily adhere and produce a biofilm

  • The biofilm in inaccessible to antimicrobials unless they are aerosolized

• As bacteria proliferate within the endotracheal tube, they may be dislodged into the lower airway because of airflow, suctioning, or bronchoscopic procedures

Exogenous Sources of Bacteria Associated with Biofilm Formation of VAP

Contaminated respiratory equipment

The environment

Healthcare provider’s hands

Endogenous Sources of Bacteria Associated with Biofilm Formation of VAP

• Endogenous bacteria

  • Normal oral flora is typically a mixed population of bacteria

  • In critical illness aerobic Gram-negative bacteria predominate

    • Change in type and increased numbers of bacteria attributed to lack of oral hygiene seen with normal swallowing that results in the spread of saliva which contains proteases, immunoglobulins, and enzymes

    • Antimicrobials can also change the population and increase resistance of oral flora

• Gastric bacteria

  • Critically ill patients receiving gastric antacid medications show greater rates of gastric colonization than those who do not

  • Enteral feeding has been associated with the development of VAP in humans

What type of bacteria represent the majority of VAP cases?

Aerobic

Ventilator-Associated Condition

• At least 2 days of worsening oxygenation following at least 2 days of stability on the ventilator based on changes to the fraction of inspired oxygen or positive end-expiratory pressure

  • Include all forms of ventilator induced lung injury as well as infection-related ventilator-associated conditions (IVACs)

Infection-Related Ventilator-Associated Condition (IVAC)

• IVACs are diagnosed based on elevated or reduced body temperature, leukocytosis, or leukopenia, and a new antimicrobial agent that is started and continued for 4 or more days

Possible Ventilator-Associated Pneumonia

• Possible VAP can be diagnosed after an IVAC has been diagnosed - when purulent secretions from lungs, bronchi, or trachea contain 25 or more neutrophils and 10 or less squamous epithelial cells per low power field or a positive culture of sputum, endotracheal aspirate, bronchoalveolar lavage, lung tissue, or protected specimen brushing is found

Probable Ventilator Associated Pneumonia

• Probable VAP can be diagnosed when either purulent respiratory secretions are found (as stated in possible VAP) and a positive quantitative/semi-quantitative culture is found, or a positive pleural fluid culture is obtained not from an indwelling chest tube or lung histopathology

Modified Centers for Disease Control and Prevention Surveillance Definitions for Ventilator-Associated Pneumonia (PNU1)

Imaging Test Evidence (Two or More Serial Chest Imaging Test Results with at Least One of the Following)

• New and persistent or progressive and persistent

  • Infiltrate

  • Consolidation

  • Cavitation

Signs/Symptoms

• At least one of the following

  • Fever

  • Leukopenia or leukocytosis

• And at least one of the following

  • New onset or change to purulent sputum or increased respiratory secretions

  • New onset or worsening cough or respiratory distress

  • Evidence of worsening gas exchange (e.g. oxygen desaturation, increased oxygen requirements, or increased ventilator demands)

  • Crackles or bronchial breath sounds

Laboratory

• At least one of the following

  • Organism identified from blood, pleural fluid, or lung tissue culture

  • Positive culture or 5% or more cells with intracellular bacteria from lower respiratory tract

  • Appropriate histopathologic evidence

Patients must fulfill all three (Imaging, Signs/Symptoms, and Laboratory) criteria

VAT

• VAT is an infection of the tracheobronchial tree of similar origin to VAP but does not affect the pulmonary parenchyma

  • May produce the same clinical signs as VAP

What is indicated if the patient fulfills the criteria for VAT/VAP?

Thoracic imaging

• A new or progressive pulmonary infiltrate on thoracic imaging is required to diagnose VAP

Limitations for Airway Sampling for Microbial Culture

• Endotracheal aspirates may represent colonization of the endotracheal tube rather than true infections

• If a nonbronchoscopic techinque is used, fluid from a noninfected part of the lung may be sampled

• May take up to 48-72 hours for culture results to return

Nonpharmacologic Strategies for Prevention of VAP

Provide educational program for caregivers and monitoring of compliance

Use of strict alcohol-based hand hygiene

Minimize time of intubation with weaning protocols

Do not change ventilatory circuit unless contamination occurs

Aspiration of subglottic secretions

Maintain endotracheal tube cuff pressure at 25 cmH2O or more

Minimize nurse to patient Ratio

Pharmacologic Strategies for Prevention of VAP

Perform oral care with dilute chlorhexidine

Avoid increasing gastric pH prophylactically

• Favorable effects seen with 0.12-2% chlorhexidine

• Performing oral antisepsis 2-4 times a day recommended

• Routine use of gastric antacid drugs is not recommended in any species on mechanical ventilation

  • Reserve for use in cases of demonstrated gastrointestinal ulceration

Treatment for VAP

• Initiation of antimicrobial therapy for VAP should commence as soon as there is clinical suspicion and airway microbiological samples have been taken and analyzed

Risk Factors for MDR Organisms in VAP

• Prior antimicrobial use within 90 days

• Septic shock at the time of diagnosis

• Acute respiratory distress syndrome preceding VAP

• Hospitalization for 5 or more days prior to occurrence of VAP

Antibiotics for Treatment of VAP

• Use of an antipseudomonal antimicrobial empirically such as a fluoroquinolone, piperacillin-tazobactam, or ceftazidime for VAP is recommended due to its high prevalence in this disease

• Carbapenems are a reasonable empiric option for dogs and cats when risk factors for MDR organisms are present

• IV aminoglycosides aren't used as monotherapy because of their poor penetration into infected lung tissue

Aerosolized Antimicrobials for Treatment of VAP

• Aerosolized antimicrobials have the potential advantage of achieving high drug concentrations in the lungs and potentially reaching biofilms while avoiding systemic absorption and toxicities

  • Aminoglycosides or polymyxins most commonly used

    • Both have concerns for nephrotoxicity

  • Use an ultrasonic or vibrating plate nebulizer with mechanical ventilation to maximize delivery to site of infection

  • Current recommendations are to include inhaled antimicrobials when VAP is due to Gram-negative bacilli (e.g. Acinetobacter spp or Pseudomonas aeruginosa) that are susceptible to only aminoglycoside or polymyxins

How long should the course of antimicrobials for treatment of VAP be?

• Majority of infections can be treated by a course of appropriate antimicrobials for a total duration of 7 days

• If a fermenting Gram-negative bacillus is cultured, a 14- to 21-day course of antimicrobial therapy should be considered