Ventilator-associated Infection: The Role for Inhaled Antibiotics

Lucy B. Palmer


Curr Opin Pulm Med. 2015;21(3):239-249. 

In This Article

Pathophysiology of Respiratory Infections and the Rationale for Inhaled Therapy

Difficulty in treatment is understandable when one examines the pathway of microbial transfer from the oropharynx to the tracheobronchial tree, and to the more distal alveolar tissue. Figure 1 shows the airway of an intubated critically ill patient and all the contributing factors that may lead to respiratory infection with resistant organisms that are difficult to treat. Pathogenic bacteria that are frequently MDR organisms (MDROs) colonize the oropharynx of critically ill patients before or soon after intubation. Within 24 h of the placement of the endotracheal tube, there is localized injury to the mucosa near the cuff, and mucociliary clearance is dramatically impaired. The pathogens that colonize the oropharynx enter the proximal airway directly from micro-aspiration. Oral secretions then pool near the cuff and migrate under the cuff to the more distal airway. Alternatively, organisms may have a direct entry into the lung via the lumen of the endotracheal tube from bacteria residing in the ventilator circuit. This process may progress from colonization to infection in the tracheobronchial tree and is called VAT.[31]

Figure 1.

The multifactorial process that leads to VAT and VAP. Subglottic secretions, disturbed mucociliary clearance, damaged mucosa, and bacterial biofilm may all play a role in the pathogenesis of proximal and distal infections. Within a few days of ICU admission, the bacteria frequently become MDROs. *The cut-off of 104 colony-forming units per milliliter for the microbiological diagnosis of VAP may not pertain to patients with prolonged mechanical ventilation. Reproduced from Palmer et al. [51].

Increasing attention is being paid to the process outlined above. VAT has been viewed in two distinct paradigms (Table 1). The differences are important as they could effect treatment decisions. The first paradigm emphasizes evidence of local infection, the lack of deep lung infection, and signs of systemic toxicity such as fever and increased white count.[32,33]

The second paradigm views VAT as an anatomic area of suppurative infection which may or may not have systemic signs of infection associated with it, and the presence of radiographic changes does not preclude it.[34] The hypothesis is that it represents an area of infection that may not respond well to systemic antibiotics. Major factors for lack of response may include: the concentrations in the airway may be lower than in the bloodstream, the bacteria in this environment may require 10–25 times the minimum inhibitory concentration for bactericidal activity,[35] and the presence of biofilm may decrease the efficacy of systemic antibiotics due to lack of penetration.[36] When VAP is present and treated with systemic antibiotics, this more proximal area of infection may persist and act as a reservoir of infected secretions that continue to promote recurrent infections. Alternatively, if ventilator-associated tracheobronchitis-anatomic (VAT-A) is present its early treatment may prevent progression to VAP.