Current Respiratory Medicine Reviews - Volume 6, Issue 1, 2010

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Endotracheal tubes (ETT) of intubated patients are constantly challenged with abundant bacteria-laden secretions. Quickly those bacteria may organize in a well-organized structure (biofilm) which is difficult to eradicate. Fragments can detach spontaneously or become dislodged by suction catheters and enter the lungs representing a source of infection. Recently several strategies have been developed to prevent bacterial biofilm formation and secretion accumulation. In this review we summarized published studies on ETT-biofilm prevention. Numerous antimicrobial-impregnated ETT have been designed to provide either bactericidal/static properties, or to prevent adhesion of bacteria on its surface. In vitro experiments and animal-studies showed several success rates in the prevention of bacterial colonization of the tube. Up to now, only two coatings, silver-hydrogel and silver-sulfadiazine in polyurethane, have been tested in clinical trials. Both proved to prevent/lower bacterial colonization of the ETT, while only the silver-hydrogel coating decreased bacterial colonization of lungs in a large multicenter study. Another innovative approach is to reduce contaminated-secretions in the ETT-lumen with novel medical devices designed to retrieve accumulated-mucus from the ETT/trachea. The mucus shaver and the mucus slurper are intended to reduce loaded-bacteria secretions from within the ETT/trachea. While experimental studies are promising, no clinical trials have been performed yet to prove this novel concept.

Any important aggression toward our bodies leads to a complex systemic inflammatory response that can be expressed by biomarkers. Thus biomarkers can help us to diagnose and manage the initial aggression. Application of biomarkers to ventilator-associated pneumonia (VAP) has two additional difficulties: the lack of universal consensus regarding the diagnostic criteria and the difficulty of discriminating the inflammatory response secondary to VAP in a context (that of ventilated critical-care patients) in which there is already a nonspecific inflammatory response. However, biomarkers have been studied in VAP and promising results have been achieved concerning diagnosis and follow-up. The most studied biomarkers have been C-reactive protein, procalcitonin, sTREM-1 and cytokines. Nevertheless, heterogeneicity of results makes difficult to apply conclusions to the general ICU population. Authors differ in VAP diagnosis criteria and in the selection of the control group (in some studies other infections different from VAP cause changes in serum biomarkers). The true diagnostic value of these substances lies in reinforcing the habitual clinical algorithm; when interpreting the results, we should take into consideration all the factors that may modify the inflammatory response.

Pseudomonas aeruginosa is one of the most frequent causative microorganisms of ventilator-acquired pneumonia (VAP). Tracheobronchial colonization (TBC) by Candida species is frequent ventilated patients. Clinical studies have found evidence of interactions between Candida and Pseudomonas, with Candida colonization possibly increasing the risk for Pseudomonas VAP. Very few animal studies have been performed stating either an indifferent or a facilitating role of previous C. albicans TBC on the development of murine P. aeruginosa pneumonia. In vitro, P. aeruginosa forms a biofilm on C. albicans filaments and ultimately kills them. In contrast, P. aeruginosa neither binds to nor kills yeast-forms C. albicans. In the presence of P. aeruginosa, C. albicans grows essentially as a yeast-form to avoid P. aeruginosa-dependant killing. This strategy of resistance operates through the detection of P. aeruginosa quorumsensing (QS) molecule 3OC12-HSL. Moreover, C. albicans produces farnesol, a cell-cell signaling molecule that induces decreased production of the QS molecule, Pseudomonas quinolone (PQS) signal and the virulence factor pyocyanin in addition to inhibit P. aeruginosa swarming mobility. By reviewing the advances made in the understanding of context-specific interactions of C. albicans and P. aeruginosa, we get an understanding on how these microorganisms mutually influence their lifestyle in the respiratory tract of critically ill patients.

Pseudomonas aeruginosa (P. aeruginosa) is a Gram-negative, aerobic, rod-shaped and polar-flagella bacterium with unipolar motility, and an opportunistic pathogen responsible for ventilator-acquired pneumonia (VAP). VAP due to P. aeruginosa is usually multidrug-resistant and associated with severe infection and increased mortality. The large genome and the high level of gene regulation may explain part of the significant virulence and of the prominent adaptability to different environments of this pathogen. In this review, we discussed the potential relationship between some of the virulent factors of P. aeruginosa and outcome of patient with VAP.

Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in the intensive care unit, and it is associated with prolonged hospitalization, increased health care costs, and high attributable mortality. Inflammatory changes in the pulmonary compartment as observed in acute lung injury are also often seen in VAP, and similar observations are now made regarding pulmonary coagulation changes. In the current review we will discuss the role of these coagulation changes in VAP (coagulopathy). We will discuss how mechanical ventilation affects both VAP and coagulopathy. As well as the role of anticoagulant therapies to reduce coagulopathy; from a theoretical perspective and from limited experimental research. And finally we will outline future research in this field.

The evidence that genetic factors are involved in risk and outcome of pneumonia is clear. Most likely genetic factors play a role in risk of VAP in a subgroup of patients as well. In the past years, a large number of polymorphisms in diverse inflammatory genes have been identified as candidates to explain genetic variability in susceptibility to pulmonary infections and its adverse outcomes. Despite the number of variations already discovered, the clinical implications remain unclear. The need to advance from simple statistical significance to biological understanding is clear. Future welldesigned studies will need to address the extremely complex gene-gene and gene-environment interactions, particularly in ventilator-associated pneumonia. Large collaborative efforts creating exquisitely detailed (both clinically and microbiologically) cohorts are required to establish this rigorous approach and produce replicable results. Complementary translational studies of the functionality of the genetic variations identified are needed. Despite the criticisms raised, early examples of pharmacogenetics aspects of infectious diseases have been shown. Hopefully this renewed approach will take a step further in accomplishing the enormous promise of genetics and personalized medicine.

Selective digestive decontamination (SDD) has been proposed as a strategy for pneumonia prevention in ICU patients that has been reported to reduce both ICU-acquired infection rates, and mortality. Numerous studies over the past 25 years have been conducted, with mixed results, but meta-analysis has supported a survival benefit to this application of prophylactic antibiotics to the oropharynx and stomach, particularly when combined with a short-course (4 days) of systemic antibiotics. Recently 4 prospective studies have reported a mortality benefit from using the SDD approach. In spite of these possible benefits, widespread use of SDD in all ICU patients should not be encouraged. In many studies, the benefits have applied only to selected populations such as surgical and trauma patients, with less benefit to medical patients. In addition, those at the extremes of disease severity (mild or severely ill) may not benefit. The major concern with use of SDD is that it probably needs to be used in all patients in a given ICU, and this widespread use has been shown in some studies to promote the emergence of resistant bacteria, particularly gram-positives such as MRSA. This is likely to be an even greater problem in ICU's with a high baseline rate of resistance. SDD has also been reported to lead to an increased rate of hospital-acquired infections in patients after they leave the ICU. In addition, there remain questions about whether a similar benefit could be obtained with only oral decontamination, even done with antiseptics and not antibiotics. Finally, many ICU's are employing non-antibiotic VAP prevention strategies, which have been successful, especially when bundled together, and it is uncertain if SDD adds incremental benefit to these efforts.

Ventilator-associated pneumonia (VAP) is a common complication in intubated and mechanically ventilated patients. A tracheostomy has been suggested to benefit patients with prolonged need for mechanical ventilation and may protect against VAP. However, a causal relationship between tracheostomy and VAP has also been suggested. This manuscript reviews the literature regarding the (causal) relationship between tracheostomy and VAP in adult critically ill patients.

Purpose of Review: This review focuses on the pathophysiology of proximal airway infection in the ventilated patient. Ventilator-associated tracheobronchitis (VAT) is increasingly recognized as an important entity not only as an essential step in the pathway from oral colonization to deep lung infection but also as an infection associated with its own morbidity. Recent Findings: Multiple recent clinical trials have focused on the effects of new devices and treatment protocols on the morbidity associated with the progression of airway colonization to VAT or with the progression of VAT to VAP. Continuous subglottic secretion suctioning (CASS), innovative types of endotracheal tubes, and targeted therapy for VAT in recent investigations have shown promise in improving clinical outcomes in the critically ill patient. However, even with diligent attention to all the modifiable risk factors for respiratory infection, complete elimination of VAT and VAP remains unlikely. As long as a patient requires an endotracheal tube which disturbs airway integrity, host defenses will be impaired, and resistant virulent organisms which result from our liberal use of systemic antibiotics will continue to challenge critical care specialists. Summary: This review will focus on: 1) the current understanding of the pathogenesis of VAT, 2) modifiable risk factors, and 3) new approaches to treatment and bacterial resistance challenges.

Oropharyngeal colonization with pathogenic organisms is a near-universal occurrence in critically ill patients receiving mechanical ventilation. Aspiration of these bacteria from the oral cavity and pharynx into the lower respiratory tract contributes to the development of ventilator-associated pneumonia (VAP). Colonization of dental plaque by Gramnegative bacteria has been recognized as an important contributor to the oropharyngeal bacterial pool in ICU patients. Lack of spontaneous movements of the tongue and jaws, reduction of salivary flow, infrequent swallowing, and inability to clean oral cavity and brush teeth because of orotracheal intubation or altered mental status result in biofilm and dental plaque formation. Oral hygiene has been proposed as a key intervention for reducing VAP. Strategies to eradicate oropharyngeal colonization by antiseptic oral care, such as chlorhexidine have been shown to reduce the oral microbial colonization and risk of VAP but failed to reduce duration of mechanical ventilation, ICU length of stay or mortality. Using chlorhexidine for oral antisepsis is simple and inexpensive with a low level of adverse effects but optimal concentration, technique and frequency of application warrant further studies.

Opioids are routinely used to provide analgesia in mechanically ventilated patients. Opioid use is associated with increased risk of ICU-acquired infection, particularly VAP. Prolongation of exposure to mechanical ventilation, microaspiration, gastrointestinal motility disturbances, and immunomodulatory effects are the potential mechanisms by which opioids may favour VAP in these patients. Activation of sympathic nervous system, and hypothalamic-pituitaryadrenal axis was identified after morphine withdrawal. In addition, suppression of mitogen-stimulated proliferation of T and B-lymphocytes, natural killer activity, antibody production, IL2, IL12, INFγ, and NO production are the main immune effects observed during acute and chronic morphine exposure. The use of short acting opioids is associated with shorter duration of mechanical ventilation and ICU stay, and might be helpful in preventing VAP. Future studies should compare the effect of different opioid agents, and the impact of progressive opioid discontinuation compared with abrupt discontinuation on VAP incidence.