Introduction

Ventilator-associated pneumonia has a high mortality rate (up to 40%) and has serious complications, such as Acute Respiratory Distress Syndrome (ARDS)/Acute Lung Injury (ALI).  In patients on mechanical ventilation the cumulative risk of pneumonia increases with the duration of ventilation.

Risk factors for ventilator-associated pneumonias include pre-existing sinusitis and the administration of paralytic agents but the presence of an endotracheal tube is potentially a contributor. Macro- or micro-aspiration of the oropharyngeal or gastric contents into the lower respiratory tract can occur via the outside of the endotracheal tube; another possible route of infection could be by inhalation of infective particles dislodged from the inside of the endotracheal tube.

Many species, including Pseudomonas aeruginosa and Staphylococcus aureus, produce biofilms, which surround the organisms when attached to endotracheal tubes, and make them relatively resistant to the actions of antibiotics and host defences. The surviving organisms may play a role in relapses by shedding infective particles from the endotracheal tube into the lower respiratory tract.

Probable routes of transmission of pathogens leading to nosocomial pneumonia

Aetiology of ventilator-associated pneumonia

Several factors affect the aetiology of ventilator-associated pneumonia:

• Time of onset after hospitalisation
• Stress-induced flora change
• Antibiotic-induced flora changes
• Exposure to contamination with nosocomial pathogens
• Patient interventions.

Certain patient characteristics indicate possible pathogens: Haemophilus influenzae is more common in patients with chronic lung disease, and Staphylococcus aureus is seen more often in the elderly, diabetics and patients with renal failure as well as following head injury, neurosurgery or recent influenza.  

Acute lung injury can be complicated by or can result from ventilator-acquired pneumonia. 

Diagnosis of ventilator-associated pneumonia

Clinical

Pneumonia is difficult to diagnose in mechanically ventilated patients, because many of the diagnostic criteria for pneumonia in non-ventilated patients are not specific to infection in mechanically ventilated patients and may be associated with non-infective disorders such as acute lung injury.  Factors complicating diagnosis include:

• Lack of respiratory symptoms in sedated patients on mechanical ventilation
• The isolation of potential pathogens from endotracheal secretions does not necessarily reflect the flora of the lower respiratory tract.

A number of attempts have been made to develop diagnostic techniques to improve the specificity of the diagnosis, including invasive bronchoscopic techniques, but this has not yet been reliably achieved. Therefore, the diagnosis of ventilator-associated pneumonia is still based on a combination of radiological and clinical criteria.

Microbiology

Management of ventilator-associated pneumonia

Early recognition and appropriate management of ventilator-associated pneumonia reduces the incidence of complications such as acute lung injury, multiple organ dysfunction and respiratory decompensation. 

Empirical therapy should be started as a matter of urgency if infection is identified. 

Unnecessary delay in antibiotic therapy leads to adverse outcomes, particularly if the patient is septic.  However, antibiotic therapy for non-infective syndromes is also detrimental.  It is important to balance the risks and benefits of treatment and this is a matter for individual clinical judgement. 

Consult your microbiologist and ITU consultant.

Antibiotic rationale

Empirical therapy will usually take into account:

• Time of onset of illness (<5 vs. ³5 days after admission) and therefore probable pathogens
• Previous antibiotic administration (rates of Pseudomonas aeruginosa or Acinetobacter spp. infection increase significantly in patients treated with antibiotics within 10 days before the onset of pneumonia)
• Severity and speed of progression of the illness
• Local pathogens and resistance patterns
• Other patient-related factors such as renal or hepatic impairment.

Therapy should be broad-spectrum, and have high activity against the probable pathogens. In patients previously untreated with antibiotics the predominant pathogens are Gram-positive cocci in ‘early’ infections and aerobic Gram-negative bacilli in ‘late’ infections.

There are some data to suggest that monotherapy may be as effective as combination therapy in severe ventilator-associated pneumonia.  However, there is considerable debate about the merits of monotherapy in these patients largely because of some limitations in the data, particularly the range of infections included in the trials, the sample sizes and the use of sub-optimal doses of aminoglycosides. Combination therapy has the advantage of giving cover against a broader-spectrum of organisms and some combinations have a synergistic mechanism of action which reduces the potential for resistance developing during treatment, eg. an aminoglycoside with a beta-lactam. 

Pseudomonas aeruginosa has been associated with resistance developing during the course of treatment and therefore if pseudomonal involvement is suspected, vigorous anti-pseudomonal therapy is indicated.

Empirical therapy

Given that there is minimal margin for error in seriously ill patients, it would be prudent to use empirical combination therapy.  Factors to be considered include:

• Previous antibiotic therapy
• Known prevalence and resistance patterns
• Patient condition.

As many second and third-line antimicrobials are associated with side-effects, a careful risk–benefit analysis must be made.  Because the process for choosing appropriate antibiotics is multifactorial, consult local guidelines and the local microbiologist.

Consult expert opinion in these infections.

If a satisfactory clinical response is observed with combination therapy after 3–4 days, monotherapy can be considered and the aminoglycoside withdrawn.

The optimal treatment duration has not been established in ventilator-associated pneumonia. Most studies report treatment durations of 7–10 days, although shorter courses may be effective.

If aspiration pneumonia is suspected, the regimen should be active against anaerobes.

Target organisms for ventilator-associated pneumonia

Antibiotic prophylaxis for ventilator-associated pneumonia

The use of antibiotics to prevent respiratory tract infections in ventilated patients has been reviewed and is controversial. If considered, this ought to be discussed between the ITU Consultant and the Medical Microbiologist on an individual patient basis.