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Ventilator-associated pneumonia (VAP) is a sub-type of hospital-acquired pneumonia (HAP) which occurs in people who are receiving mechanical ventilation. VAP is not characterized by the causative agents; rather, as its name implies, definition of VAP is restricted to patients undergoing mechanical ventilation while in a hospital. The diagnoses of VAP is difficult but usually requires a new infiltrate on chest x-ray plus two or more of: fever of >38.3°C, leukocytosis of >12 × 109/ml, purulent tracheobronchial secretions, and/or reduction in gas exchange. In order to appropriately categorize the causative agent or mechanism it is usually recommended to obtain a culture prior to initiating mechanical ventilation as a reference.
Signs and symptoms
People who are on mechanical ventilation are often sedated and are rarely able to communicate. As such, many of the typical symptoms of pneumonia will either be absent or unable to be obtained. The most important signs are fever, low body temperature, new purulent sputum, and hypoxemia (decreasing amounts of oxygen in the blood).
A diagnosis of ventilator-associated pneumonia is made when the patient has a new diagnosis of pneumonia after having mechanical ventilation initiated. VAP should be suspected in any person on mechanical ventilation exhibiting increasing numbers of white blood cells on blood testing, and new shadows (infiltrates) on a chest x-ray as is indicative of a pneumonia. Blood cultures may reveal the microorganisms causing VAP.
Two strategies exist for diagnosing VAP. One strategy collects cultures from the trachea of people with symptoms of VAP plus a new or enlarging infiltrate on chest x-ray. The other is more invasive and advocates a bronchoscopy plus bronchoalveolar lavage (BAL) for people with symptoms of VAP plus a new or enlarging infiltrate on chest x-ray. In both cases, VAP is not diagnosed when cultures are negative and another source of the symptoms is sought.
It is thought by many, that VAP primarily occurs because the endotracheal or tracheostomy tube allows free passage of bacteria into the lower segments of the lung in a person who often has underlying lung or immune problems. Bacteria travel in small droplets both through the endotracheal tube and around the cuff. Often, bacteria colonize the endotracheal or tracheostomy tube and are embolized into the lungs with each breath. Bacteria may also be brought down into the lungs with procedures such as deep suctioning or bronchoscopy. Another possibility is that the bacteria already exist in the mucus lining the bronchial tree, and are just kept in check by the body's first line of defenses.
Once inside the lungs, bacteria then take advantage of any deficiencies in the immune system (such as due to malnutrition or chemotherapy) and multiply. A combination of bacterial damage and consequences of the immune response lead to disruption of gas exchange with resulting symptoms.
The microbiologic flora responsible for VAP is different from that of the more common community-acquired pneumonia (CAP). In particular, viruses and fungi are uncommon causes in people who do not have underlying immune deficiencies. Though any microorganism that causes CAP can cause VAP, there are several bacteria which are particularly important causes of VAP because of their resistance to commonly used antibiotics. These bacteria are referred to as multidrug resistant (MDR).
- Pseudomonas aeruginosa is the most common MDR Gram-negative bacterium causing VAP. Pseudomonas has natural resistance to many antibiotics and has been known to acquire resistance to every antibiotic except for polymyxin B. Resistance is typically acquired through upregulation or mutation of a variety of efflux pumps which pump antbiotics out of the cell. Resistance may also occur through loss of an outer membrane porin channel (OprD)
- Klebsiella pneumoniae has natural resistance to some beta-lactam antibiotics such as ampicillin. Resistance to cephalosporins and aztreonam may arise through induction of a plasmid-based extended spectrum beta-lactamase (ESBL) or plasmid-based ampC-type enzyme
- Serratia marcescens has an ampC gene which can be induced by exposure to antibiotics such as cephalosporins. Thus, culture sensitivities may initially indicate appropriate treatment which fails due to bacterial response.
- Enterobacter as a group also have an inducible ampC gene. Enterobacter may also develop resistance by acquiring plasmids.
- Citrobacter also has an inducible ampC gene.
- Stenotrophomonas maltophilia often colonizes people who have tracheal tubes but can also cause pneumonia. It is often resistant to a wide array of antibiotics but is usually sensitive to co-trimoxazole
- Acinetobacter are becoming more common and may be resistant to carbapenems such as imipenem and meropenem
- Burkholderia cepacia is an important organism in people with cystic fibrosis and is often resistant to multiple antibiotics
- Methicillin-resistant Staphylococcus aureus is an increasing cause of VAP. As many as fifty percent of Staphylococcus aureus isolates in the intensive care setting are resistant to methicillin. Resistance is conferred by the mecA gene.
Treatment of VAP should be matched to known causative bacteria. However, when VAP is first suspected, the bacteria causing infection is typically not known and broad-spectrum antibiotics are given (empiric therapy) until the particular bacterium and its sensitivities are determined. Empiric antibiotics should take into account both the risk factors a particular individual has for resistant bacteria as well as the local prevalence of resistant microorganisms. If a person has previously had episodes of pneumonia, information may be available about prior causative bacteria. The choice of initial therapy is therefore entirely dependent on knowledge of local flora and will vary from hospital to hospital.
Risk factors for infection with an MDR strain include ventilation for more than five days, recent hospitalization (last 90 days), residence in a nursing home, treatment in a hemodialysis clinic, and prior antibiotic use (last 90 days).
Possible empirical therapy combinations include (but are not limited to):
- vancomycin/linezolid and ciprofloxacin,
- cefepime and gentamicin/amikacin/tobramycin
- vancomycin/linezolid and ceftazidime
- Ureidopenicillin plus β-lactamase inhibitor such as piperacillin/tazobactam or ticarcillin/clavulanate
- a carbapenem (e.g., imipenem or meropenem)
Therapy is typically changed once the causative bacteria are known and continued until symptoms resolve (often 7 to 14 days). For patients with VAP not caused by nonfermenting Gram-negative bacilli (like Acinetobacter, Pseudomonas aeruginosa) the available evidence seems to support the use of short-course antimicrobial treatments (< or =10 days).
People who do not have risk factors for MDR organisms may be treated differently depending on local knowledge of prevalent bacteria. Appropriate antibiotics may include ceftriaxone, ciprofloxacin, levofloxacin, or ampicillin/sulbactam.
As of 2005, there is ongoing research into inhaled antibiotics as an adjunct to conventional therapy. Tobramycin and polymyxin B are commonly used in certain centres but there is no clinical evidence to support their use.
Prevention of VAP involves limiting exposure to resistant bacteria, discontinuing mechanical ventilation as soon as possible, and a variety of strategies to limit infection while intubated. Resistant bacteria are spread in much the same ways as any communicable disease. Proper hand washing, sterile technique for invasive procedures, and isolation of individuals with known resistant organisms are all mandatory for effective infection control. A variety of aggressive weaning protocols to limit the amount of time a person spends intubated have been proposed. One important aspect is limiting the amount of sedation that a ventilated person receives.
Other recommendations for preventing VAP include raising the head of the bed to at least 30 degrees and placement of feedings tubes beyond the pylorus of the stomach. Antiseptic mouth washes such as chlorhexidine may also reduce the incidence of VAP. One recent study suggests that using heat and moisture exchangers instead of heated humidifiers, may increase the incidence of VAP.
American and Canadian guidelines strongly recommend the use of supraglottic secretion drainage (SSD) Special tracheal tubes with an incorporated suction lumen as the EVAC tracheal tube form Covidien / Mallinckrodt can be used for that reason. New cuff technology based on polyurethane material in combination with subglottic drainage (SealGuard Evac tracheal tube from Covidien/Mallinckrodt)showed significant delay in early and late onset of VAP.
Between 8 and 28% of patients receiving mechanical ventilation are affected by VAP. VAP can develop at any time during ventilation, but occurs more often in the first few days after intubation. This is because the intubation process itself contributes to the development of VAP.
VAP occurring early after intubation typically involves fewer resistant organisms and is thus associated with a more favorable outcome. Because respiratory failure requiring mechanical ventilation is itself associated with a high mortality, determination of the exact contribution of VAP to mortality has been difficult. As of 2006, estimates range from 33% to 50% death in patients who develop VAP. Mortality is more likely when VAP is associated with certain microorganisms (Pseudomonas, Acinetobacter), blood stream infections, and ineffective initial antibiotics. VAP is especially common in people who have acute respiratory distress syndrome (ARDS).
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