Clinical presentation and diagnosis of ventilator-associated pneumonia http://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of... biopsy can be diagnostic, but is seldom performed because of its invasiveness. Imaging — All patients suspected of having VAP should have a chest radiograph . Common abnormalities include air bronchograms, alveolar infiltrates, and silhouetting of adjacent solid organs. The chest radiograph can also help determine the severity of the disease (multilobar versus unilobar) and identify complications, such as pleural effusions or cavitation. The diagnosis of VAP requires an abnormal chest radiograph, although radiographic abnormalities alone are insufficient to diagnose VAP because they are nonspecific (ie, they frequently exist in the absence of VAP) [1,4,7,8]. In an observational study, only 43 percent of patients who had clinical and radiographic evidence of VAP at the time of their death were confirmed to have VAP by postmortem examination . Microbiology — All patients suspected of having VAP should undergo lower respiratory tract sampling, followed by microscopic analysis and culture of the specimen . Sampling methods — There are a variety of methods for sampling material from the airways and alveoli, including bronchoscopic and nonbronchoscopic (ie, blind) techniques. Bronchoscopic sampling of the lower respiratory tract is performed using either bronchoalveolar lavage (BAL) or a protected specimen brush (PSB) (see "Flexible bronchoscopy: Indications and contraindications" and "Flexible bronchoscopy: Equipment, procedure, and complications"): BAL involves the infusion and aspiration of sterile saline through a flexible fiberoptic bronchoscope that is wedged in a bronchial segmental orifice. The technique of BAL is discussed in detail elsewhere. (See "Basic principles and technique of bronchoalveolar lavage".) A PSB is a brush that is contained within a protective sheath. It is designed to minimize the likelihood that the brush will be contaminated during bronchoscopy. The procedure involves placing the bronchoscope tip next to a bronchial segmental orifice, pushing the sheath through the bronchoscope, and then advancing the brush out of the sheath and into the airway. Specimens are collected by brushing the airway wall, withdrawing the brush into the sheath, and then removing the sheath from the bronchoscope. Nonbronchoscopic lower respiratory tract sampling includes tracheobronchial aspiration or mini-BAL [9-17]. Tracheobronchial aspiration is performed by advancing a catheter through the endotracheal tube until resistance is met and then applying suction. Mini-BAL is performed by advancing a catheter through the endotracheal tube until resistance is met, infusing sterile saline through the catheter, and then aspirating. A clinician is not necessary to perform or supervise nonbronchoscopic sampling. This reduces the cost, allows specimens to be obtained quickly, and facilitates serial sampling when necessary. Bronchoscopic and nonbronchoscopic sampling for suspected VAP have been compared [18-22]. Taken together, the evidence indicates that bronchoscopic sampling does not improve mortality, length of hospital stay, duration of mechanical ventilation, or length of intensive care unit stay [18,20,22]. However, it may lead to a narrower antimicrobial regimen and/or more rapid de-escalation of antimicrobial therapy [18,19,21,23]. Microscopic analysis — The most common microscopic analysis is the Gram stain of a lower respiratory specimen (ie, tracheobronchial aspirate, BAL fluid, or mini-BAL fluid). It can be used to characterize the morphology of bacteria, as well as to semiquantitate polymorphonuclear leukocytes and other cell types. The presence of abundant neutrophils is consistent with VAP and the bacterial morphology may suggest a likely pathogen. Gram stain analysis might decrease the incidence of inappropriate antimicrobial therapy and improve diagnostic accuracy when correlated with culture results .2 de 11 23/04/2011 04:34 p.m.
Clinical presentation and diagnosis of ventilator-associated pneumonia http://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of... A differential cell count is an additional type of microscopic analysis that can be performed following a BAL. It determines the proportion of total nucleated cells in the spun sediment of BAL fluid that are neutrophils, lymphocytes, macrophages, eosinophils, basophils, or other nucleated cells. In a prospective cohort study of 39 patients, VAP was correctly excluded in all patients in whom neutrophils were fewer than 50 percent of the total nucleated cells . Quantitative culture — Quantitative cultures can be performed on specimens obtained bronchoscopically or nonbronchoscopically. VAP is supported when an established threshold of bacterial growth is exceeded. Only bacteria that are pulmonary pathogens should be counted. As an example, Staphylococcus epidermidis, most gram positive bacilli (except actinomycosis and nocardia), and enterococci should be not be counted. Thresholds of 1,000,000 colony forming units (cfu)/mL for samples obtained by tracheobronchial aspiration, 10,000 cfu/mL for samples obtained by BAL, or 1000 cfu/mL for samples obtained by PSB are most accurate because they are sufficiently high that patients with tracheobronchial colonization are unlikely to be mistaken for patients with VAP [1,25,26]. Lower thresholds are reasonable if the risk of a missing a VAP (ie, a false-negative) exceeds the risk of unnecessary treatment (ie, a false-positive) . According to a prospective cohort study of 122 patients, thresholds between 1000 and 10,000 cfu/mL for BAL specimens and between 100 and 1000 cfu/mL for PSB specimens decrease the likelihood of a false-negative result to a greater degree than they increase the likelihood of a false-positive result . In general, quantitative cultures derived from nonbronchoscopic specimens tend to have a lower specificity than quantitative cultures derived from bronchoscopic specimens [11,13]. However, this is balanced by a higher sensitivity, resulting in comparable diagnostic accuracy. In a prospective cohort study of 38 patients, the diagnostic accuracy of quantitative cultures was greatest when the sample was obtained by tracheobronchial aspiration, followed (in order of decreasing accuracy) by BAL, mini-BAL, and PSB . Quantitative cultures do not appear to improve clinical outcomes. In a meta-analysis of three randomized trials (1240 patients), quantitative cultures did not alter mortality, days of mechanical ventilation, or length of ICU stay, compared to semiquantitative culture . Despite the lack of improvement in clinical outcomes, we believe quantitative cultures are advantageous because they may lead to more judicious use of antibiotics. Semiquantitative culture — Semiquantitative cultures can also be performed on specimens obtained bronchoscopically or nonbronchoscopically. They are typically reported as showing heavy, moderate, light, or no growth . The amount of growth that suggests VAP has not been firmly established, but it is reasonable to consider a semiquantitative culture with moderate or heavy growth to be positive. Compared to quantitative cultures, semiquantitative cultures are less likely to distinguish patients whose airways are colonized from those who have VAP . As a result, false-positive results are more likely, which can lead to inappropriate therapy. Effect of antibiotics — Lower respiratory tract specimens should be collected prior to initiating antibiotic therapy because antibiotic therapy reduces the sensitivity of both microscopic analysis and culture [30,31]. Similarly, specimens should be collected prior to changing the antibiotic regimen of patients suspected of developing VAP while receiving antibiotics [26,32]. Antibiotic therapy also influences the type of pathogens that cause VAP. In a prospective cohort study of 135 patients, prior antibiotic use was independently associated with VAP due to an antibiotic- resistant pathogen, especially if the antibiotic regimen included a third generation cephalosporin, fluoroquinolone, or imipenem .3 de 11 23/04/2011 04:34 p.m.
Clinical presentation and diagnosis of ventilator-associated pneumonia http://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of... Procalcitonin — Biologic markers are sometimes used to try to distinguish between bacterial and non-bacterial causes of pneumonia. Procalcitonin is one of the most promising biologic markers. Procalcitonin is the peptide precursor of calcitonin. It is released by parenchymal cells in response to bacterial toxins, leading to elevated serum levels in patients with bacterial infections. Procalcitonin is measured by two commercially available tests, the Kryptor assay and the LUMI assay. The former is generally preferred because it has a higher sensitivity. The use of serum procalcitonin to facilitate the decision of whether to initiate antibiotics in patients admitted with suspected pneumonia has been evaluated in randomized trials [34-36]. The trials found that serum procalcitonin decreased antibiotic exposure without affecting clinical outcomes. However, most of the trials enrolled patients with suspected community-acquired pneumonia only and not patients with suspected VAP. In patients with suspected VAP, it is uncertain if serum procalcitonin levels are a useful guide for the decision of whether to initiate antibiotics because the evidence is conflicting. This was illustrated by two prospective cohort studies in which VAP was confirmed in approximately half of the cases. One study of 20 patients found that a procalcitonin level 3.0 ng/mL diagnosed VAP with a sensitivity and specificity of 78 and 97, respectively . In contrast, another study of 73 patients reported that a serum procalcitonin level ≥2 ng/mL diagnosed VAP a sensitivity and specificity of only 41 and 61 percent, respectively . Until higher quality studies resolve the uncertainty, we recommend not using serum procalcitonin levels routinely to guide the decision of whether to initiate antibiotics in patients with suspected VAP. However, there are two situations in which procalcitonin may be useful in patients with confirmed VAP: Procalcitonin may be helpful in the decision as to whether to discontinue antibiotic therapy. This was illustrated by a trial that randomly assigned 101 patients with VAP to a conventional antibiotic discontinuation strategy or a procalcitonin-guided antibiotic discontinuation strategy . The latter strategy reduced the duration of antibiotic therapy and did not affect clinical outcomes, such as mortality, hospital length of stay, ventilator-free days, or ICU-free days. Procalcitonin may be a useful prognostic marker, since progressive increases in serum procalcitonin have been associated with septic shock and mortality [40-42]. Clinical score — The Clinical Pulmonary Infection Score (CPIS) combines clinical, radiographic, physiologic, and microbiologic data into a numerical result (table 1). Initial validation of the CPIS found that a score greater than 6 correlated with VAP . However, subsequent studies failed to confirm this. In a prospective cohort study, the CPIS identified VAP with a sensitivity and specificity of only 60 and 59 percent, respectively . Lung biopsy — Histologic examination of lung tissue obtained by biopsy is an imperfect and seldom used method of diagnosing VAP. In addition to requiring an invasive procedure, its reliability and reproducibility are uncertain. This is probably due to lack of standardized histologic criteria to define VAP. In a prospective cohort study, 39 patients who died while receiving mechanical ventilation underwent4 de 11 23/04/2011 04:34 p.m.
Clinical presentation and diagnosis of ventilator-associated pneumonia http://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of... post mortem open lung biopsy . The histology was reviewed separately by four pathologists who reported a prevalence of VAP ranging from 18 to 38 percent. One pathologist reinterpreted the histology six months later and reclassified the VAP status of two patients. DIAGNOSTIC APPROACH — Ventilator-associated pneumonia (VAP) should be considered in any mechanically ventilated patient who develops new or increased fever, alveolar infiltrate, respiratory secretions, leukocytosis, or respiratory abnormalities. The latter may include an increased respiratory rate, increased minute ventilation, decreased tidal volume, decreased oxygenation, or a need for more ventilatory support or inspired oxygen. All patients with suspected VAP should have a chest radiograph (figure 1). A normal chest radiograph excludes VAP, although ventilator-associated tracheobronchitis may exist. (See "Endotracheal tube management and complications", section on Tracheobronchitis.) Patients with suspected VAP and an abnormal chest radiography should have their lower respiratory tract secretions collected for microscopic analysis and culture. This can be done bronchoscopically or nonbronchoscopically. The bronchoscopic approach probably leads to narrower antibiotic coverage, earlier de-escalation of antimicrobial therapy, and, presumably, less antibiotic resistance. However, it is invasive, less readily available, and does not appear to improve mortality, duration of mechanical ventilation, or length of stay. Sampling of the lower respiratory tract is ideally performed prior to initiating antibiotic therapy (or prior to changing the antibiotic regimen if the patient is suspected of developing VAP while receiving antibiotics). Quantitative or semiquantitative cultures are both acceptable, with the choice depending largely on availability. Sampling should not delay the initiation of necessary antibiotic therapy. Empiric antimicrobial therapy can be withheld if the clinical suspicion for VAP is low and microscopic analysis of lower respiratory tract samples is negative (ie, few neutrophils). Otherwise, empiric broad-spectrum antimicrobial therapy should be initiated, as described separately. (See "Treatment of hospital-acquired, ventilator- associated, and healthcare-associated pneumonia in adults", section on Empiric treatment.) Culture results should be available within two to three days. The decision on subsequent antibiotic therapy should take into account the culture results and the patients response to empiric therapy (figure 1): Patients with negative cultures who have not improved may not have VAP. Other diagnoses or sites of infection should be sought. Patients with negative cultures who have improved may not have VAP. Antimicrobial therapy should be discontinued, unless it is indicated for an infection other than VAP. Patients with positive cultures who have not improved probably have VAP. However, they may be receiving inappropriate antimicrobial therapy, have a complication of the VAP, have a second source of infection, or have a second diagnosis. The antimicrobial regimen should be adjusted and then complications, other sites of infection, and other pathogens should be sought. Patients with positive cultures who have improved probably have VAP, which has responded to antimicrobial therapy. Antimicrobial therapy should be narrowed according to the culture results. The treatment of VAP is discussed separately. (See "Treatment of hospital-acquired, ventilator- associated, and healthcare-associated pneumonia in adults".) SUMMARY AND RECOMMENDATIONS5 de 11 23/04/2011 04:34 p.m.
Clinical presentation and diagnosis of ventilator-associated pneumonia http://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of... Ventilator-associated pneumonia (VAP) is a type of hospital-acquired (or nosocomial) pneumonia that develops after more than 48 hours of mechanical ventilation. (See Introduction above.) VAP is usually suspected when a patient receiving mechanical ventilation develops a new or progressive pulmonary infiltrate accompanied by fever, leukocytosis, purulent tracheobronchial secretions, and/or new respiratory abnormalities. (See Clinical presentation above.) All patients with suspected VAP should have a chest radiograph performed. A normal chest radiograph excludes VAP. (See Diagnostic approach above.) Patients with suspected VAP and an abnormal chest radiograph should have a sample of their lower respiratory tract secretions collected for microscopic analysis and culture. (See Diagnostic approach above.) Empiric antimicrobial therapy can be withheld if the clinical suspicion for VAP is low and microscopic analysis of lower respiratory tract samples is negative (ie, few neutrophils). Otherwise, empiric broad-spectrum antimicrobial therapy should be initiated. (See "Treatment of hospital-acquired, ventilator-associated, and healthcare-associated pneumonia in adults", section on Empiric treatment.) Two to three days after lower respiratory tract sampling and the initiation of empiric antimicrobial therapy, the culture results should be checked and the patients response to antimicrobial therapy assessed. VAP is diagnosed on the basis of this assessment (see Diagnostic approach above): Patients with positive cultures who have not improved probably have VAP. However, they may be receiving inappropriate antimicrobial therapy, have a complication of the VAP, have a second source of infection, or have a second diagnosis. Patients with positive cultures who have improved probably have VAP that has responded appropriately to antimicrobial therapy. Patients with negative cultures may not have VAP. A diagnostic algorithm for VAP is shown in the figure (figure 1) (see Diagnostic approach above). Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171:388. 2. Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med 2002; 165:867. 3. Meduri GU. Diagnosis and differential diagnosis of ventilator-associated pneumonia. Clin Chest Med 1995; 16:61. 4. Andrews CP, Coalson JJ, Smith JD, Johanson WG Jr. Diagnosis of nosocomial bacterial pneumonia in acute, diffuse lung injury. Chest 1981; 80:254. 5. Fagon JY, Chastre J, Hance AJ, et al. Detection of nosocomial lung infection in ventilated patients. Use of a protected specimen brush and quantitative culture techniques in 147 patients.6 de 11 23/04/2011 04:34 p.m.
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