الفهرس 
Pathophysiology of ventilator associated pneumoniaOnly 14 pages are availabe for public view
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Abstract
Ventilator associated pneumonia (VAP) is a common condition between patients on mechanical ventilation, difficult to diagnose accurately, expensive to treat and hard to prevent. VAP development prolongs patient’s stay in the intensive care unit (ICU) and also is associated with significant morbidity and mortality. Moreover VAP accounts for more than 50% of the antibiotics prescribed in ICU, making it a primary focus for risk-reduction strategies (Mietto et al., 2013).
VAP is usually classified as either early onset, occurring within the first four days of mechanical ventilation or late onset, developing five or more days after initiation of mechanical ventilation (Joseph et al., 2009).
The complex interplay between the endotracheal tube, presence of risk factors, virulence of the invading bacteria and host immunity largely determine the development of VAP. The presence of an endotracheal tube is by far the most important risk factor, resulting in a violation of natural defense mechanisms (the cough reflex of glottis and larynx) (Kalanuria et al., 2014).
The diagnosis of VAP is challenging. While early diagnosis is essential to improve the outcomes, there is also a concern about accuracy of diagnosis to prevent overuse of antibiotics. The gold standard for diagnosis is a combination of histopathology and culture of lung tissue (Lodha and Kabra, 2011).
To facilitate the diagnosis of VAP, a combination of various parameters may be useful. The Clinical Pulmonary Infection Score (CPIS) was developed by using a combination of six clinical, radiologic, and microbiologic criteria: temperature, white cell count, sputum, oxygenation, culture of tracheal aspirates, and radiology; each parameter was scored from 0 to 2 and a total score of >6 points suggested a diagnosis of VAP (Lodha and Kabra, 2011).
Optimal antimicrobial therapy of VAP is critically important, because inadequate initial antimicrobial therapy has consistently been associated with increased mortality. However, excessive antimicrobial therapy leads to unnecessary treatment-related complications and costs and contributes to a further increase in the prevalence of antimicrobial resistance. Antimicrobial regimen is selected initially, to ensure adequate coverage for all potential pathogens, even those with multidrug resistance. On the other hand, antimicrobial treatment, especially for prolonged broad-spectrum antimicrobial treatment, exhibits a considerable microbial selection pressure and is associated with an excess mortality due to pneumonia through the selection of MDR microorganisms. Also, delayed appropriate antimicrobial therapy is associated with excess mortality in VAP and severe sepsis. Once microbiology results are available, and after observing the clinical response the initial empiric regimen can be narrowed or discontinued to prevent unnecessarily broad or prolonged antimicrobial use and its attendant risks and costs (Park, 2005).
The rate of VAP caused by multidrug resistant strains has increased in recent years. For these strains, especially for Gram-negative multidrug resistant bacilli, minimum inhibitory concentrations (MIC) of still active antibiotics, mainly aminoglycosides, are high and toxic (Rouby et al., 2015).
The role of inhaled antibiotics, which achieve high drug concentrations in the target organ, seems to be clear for the eradication of MDR bacteria and for the treatment of Gram-negative respiratory infections in patients with cystic fibrosis or bronchiectasis. Inhaled antibiotics could also play a beneficial role in the management of nosocomial acquired pneumonia, mainly VAP due to MDR Gram-negative bacteria. (Michalopoulos and Papadakis, 2010).
In addition, the relevant guidelines by the American Thoracic Society and the Infectious Diseases Society of America note that ‘‘aerosolized antibiotics may be considered as adjunctive therapy in patients with MDR gram-negatives who are not responding to systemic therapy’’ (American Thoracic Society/Infectious Disease Society of America, 2005).
However, most recent studies on inhaled antibiotics and their effect on VAP suggest that inhaled therapy may have a beneficial effect decreasing the emergence of resistance and achieving very high antibiotic concentrations which may eradicate the highly resistant organisms (Palmer, 2015).