Ventilator associated tracheobronchitis: A call for more evidence.

Intubation and mechanical ventilation, life-saving measures for many patients in respiratory failure, are associated with risk of complications including infections such as ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). VAP has been well studied and known to increase cost, the length of stay, and mortality; consequently, garnering great interest in prevention, early detection, and appropriate treatment. In comparison to VAP, the studies on VAT are limited in number and have yielded conflicting conclusions on patient outcomes. Therefore, VAT management and treatment continue to be hotly debated, such that the 2016 Infectious Disease Society of America (IDSA) and American Thoracic Society's (ATS) guidelines on hospital-acquired pneumonia weakly recommend not treating VAT.[1]

Putting the controversy aside for now, there are similarities between VAT and VAP. They both manifest after 48 h of intubation and have similar microbiomes. Common multi-drug resistant organisms found in both conditions are Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae, with or without extended-spectrum beta-lactamase inhibitors.[23] It is believed that VAT is a risk factor for VAP and pathogenesis for both VAT and VAP originate from compromised immunity and oral bacterial colonization. Subsequently, there is microaspiration either around the endotracheal tube cuff through mucosal folds or through the tube lumen itself which may be coated with an adherent biofilm, leading to distal airway infection and/or lower respiratory infection.[4] Therefore, prevention of VAP has largely focused on decreasing the burden of oropharyngeal and enteric flora and preventing microaspiration. In 2012, several health-care societies worldwide started “bundling” practices for the prevention of VAP including positioning the patient with the head of the bed elevated up 30° or more, chlorhexidine oral care, and daily interruption of sedation and assessment for readiness to wean.[5] The National Health Service Modernisation Agency in the United Kingdom added routine subglottic secretion drainage.[6] The ventilator bundle has since been validated throughout the world to decrease the incidence of VAP, mechanical ventilator days, Intensive Care Unit (ICU) length of stay, health-care costs, and mortality. Although the effect of these preventive measures on VAT is not well studied, if we presume colonization, VAT, and VAP are a continuum, then it follows that the incidence of VAT should also improve with the VAP bundle.

In this issue of the journal, Ray et al.[7] present the first study in India to examine the incidence of VAT. They used the most common criteria to diagnosis VAT: fever (>38°C) with no other recognizable cause, purulent sputum production, positive endotracheal aspirate (ETA) cultures, and no new radiographic signs indicating pneumonia.[4] Another strength of their study is that cultures were prospectively collected when patients were clinically symptomatic. Thus, positive cultures were more likely to represent disease states rather than colonization. They considered pathogenicity with positive ETA gram-stain and semi-quantitative ETA cultures with moderate to heavy growth. Gram-stain with bacterial presence approximates >1 × 105 organisms/mL, and moderate-to-heavy growth on semi-quantitative culture approximates >1 × 106 colony-forming units (cfu/mL).[48] Although these techniques are widely used, cost-effective, and endorsed as the preferred collection method by IDSA/ATS, gram-stain is a better tool to rule out VAP. It is not sensitive and specific enough to serve as a sole guide for antimicrobial choice or to discriminate colonization from actual clinically significant infection (negative predictive value 91% with a 20%–30% VAP prevalence, sensitivity 79% and specificity 75%, respectively).[9] Quantitative cultures with a cut-off of 1 × 106 cfu/mL represent a wide-range of sensitivity 50%–70% and specificity of 70%–85%.[1011] This may be insufficient to fully distinguish between colonization and infection for equivocal cases, such that the clinician may need to consider invasive measures, such as bronchoscopy to obtain bronchoalveolar lavage (with cut-off threshold of ≥1 × 104 cfu/mL) or protected brush specimen (≥1 × 103 cfu/mL).[4] Portable chest radiograph may not be sensitive enough to detect new infiltrates in the setting of a preexisting abnormal chest radiograph, which can be found in up to 38% of mechanically ventilated patients.[2] On the other hand, chest computed tomography scans are costly and impractical to perform for all patients.[12] Hence, early VAP and VAT are difficult to differentiate. Future studies with more sensitive modalities such as bedside lung ultrasonography show promise in this regard.[1314]

The authors' findings are right in line with the general incidence and microbiome for VAT.[15] They propose, despite good adherence to the ventilator bundle, that the relatively higher incidence of VAT noted in their study may be due to the lack of regular tracheal cuff monitoring or inappropriate suctioning techniques. A recent meta-analysis by Roquilly et al. found that the above mentioned preventative techniques may not be as impactful on outcomes as we have conventionally thought.[16] The meta-analysis also suggests more promise in less utilized modalities not currently included in most bundles, such as sinusitis prophylaxis, selective digestive and oropharyngeal decontamination, subglottic secretion drainage, and early enteral and postpyloric feeding. However, many studies have shown that good adherence to the basic ventilator bundle correlated with improved outcomes including mortality.[171819] The current ventilator bundle remains a valuable preventive tool with room for additional improvements based on new evidence.

We applaud the authors for bringing attention to VAT as a major problem in ICUs worldwide. We hope to see a future comprehensive study from this group or others reporting on outcome data like mortality, health-care cost burden, and antimicrobial treatment practices. Published literature on VAT will hopefully spur future interest in larger studies including collaborative global networks to elucidate the impact of practical prevention, to establish best practices for realistic and cost-effective management and treatment, and to improve clinically significant outcomes.

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