Ventilator-associated pneumonia (VAP) is pneumonia that develops 48 hours or longer after mechanical ventilation is given by means of an endotracheal tube or tracheostomy. Ventilator-associated pneumonia (VAP) results from the invasion of the lower respiratory tract and lung parenchyma by microorganisms. Intubation compromises the integrity of the oropharynx and trachea and allows oral and gastric secretions to enter the lower airways.
Hospital-acquired pneumonia (HAP) is pneumonia that develops 48 hours or longer after admission to a hospital. HAP is the second most common nosocomial infection. HAP increases a patient's hospital stay by approximately 7-9 days and can increase hospital costs by an average of $40,000 per patient.[1, 2, 3, 4, 5]
Health care–associated pneumonia is pneumonia that occurs in persons in one of the following groups:
Multiple factors should be considered when addressing the issues of HAP and VAP. These factors include the following:
For other discussions on pneumonia, see the following:
Ventilator-associated pneumonia (VAP) is a complication in as many as 28% of patients who receive mechanical ventilation. The incidence of VAP increases with the duration of mechanical ventilation. Estimated rates are 3% per day for the first 5 days, 2% per day for days 6-10, and 1% per day after day 10.[6]
The crude mortality rate for VAP is 27-76%. Pseudomonas or Acinetobacter pneumonia is associated with higher mortality rates than those associated with other organisms. Studies have consistently shown that a delay in starting appropriate and adequately dosed antibiotic therapy increases the mortality risk.
A systematic review and meta-analysis by Melsen et al found no evidence of mortality attributable to VAP in patients with trauma or acute respiratory distress syndrome. Pooled data on 17,347 patients showed that among trauma patients, the estimated relative risk was 1.09 (95% confidence interval [CI], 0.87-1.37), and among patients with acute respiratory distress syndrome, the relative risk was 0.86 (95% CI, 0.72-1.04). Melsen et al found evidence for mortality attributable to VAP among other patient subgroups, but this risk could not be quantified because of heterogeneity in study results.[7]
Outcomes are also related to the timing of the onset of VAP. Early-onset pneumonia occurs within the first 4 days of hospitalization, whereas late-onset VAP develops 5 or more days after admission. Late-onset pneumonias are usually associated with multidrug-resistant (MDR) organisms.
The patient's medical history should include an assessment for risk factors related to multidrug-resistant (MDR) pathogens. Such risk factors include the following:
This assessment is important so that appropriate empiric antibiotics can be initiated before bacterial culture results return. If appropriate empiric antibiotics are selected, the subsequent adjustment of antibiotics does not improve the patient's mortality risk.
The diagnostic triad for VAP consists of the following clinical criteria:
When the combination of radiologic infiltrates and 2 clinical criteria are observed, the sensitivity of diagnosing VAP is 69% and the specificity is 75%.[8]
Intubation with mechanical ventilation increases the risk of hospital-acquired pneumonia (HAP) 3- to 21-fold[8, 9, 10, 11] and should be avoided if possible. Noninvasive positive-pressure ventilation is an option to consider, especially in the following groups:
Patient position can be associated with an increased incidence of HAP and VAP. The incidence of HAP is increased in supine patients when compared with semirecumbant patients,[12] although there no difference in mortality.
Continuous aspiration of subglottic secretions reduces the risk of early-onset VAP. Results of a randomized, controlled trial showed a significant reduction in VAP (relative risk reduction of 42%), including late-onset VAP, when subglottic secretion drainage was performed while patients were on mechanical ventilation.[13] Cuff pressures should be maintained at greater than 20 cm of water to prevent aspiration around the endotracheal tube.
Passive humidifiers or heat moisture exchangers are preferred to reduce colonization of the ventilator circuit. Ventilatory-circuit condensation should be prevented from entering the endotracheal tubes and any inline nebulizer. Frequent changes of the ventilator circuit, however, have not been shown to reduce the risk of VAP and are currently not recommended.
Protocols for sedation and weaning should be applied in the ICU to reduce the duration of mechanical ventilation.
Placing patients in a semirecumbent position is associated with approximately a 3-fold reduction in the risk of hospital-acquired pneumonia (HAP),[12] especially during enteral feeding.
Early enteral feeding is currently recommended. Although this route of feeding is associated with an increased incidence of HAP, it offers a number of advantages in delivering nutrition. Investigators have compared the risks of ICU-acquired HAP between gastric and postpyloric feeding. Individual studies have shown no significant differences. A meta-analysis of these studies has suggested a significant reduction in ICU-acquired HAP.[14]
In a prospective, randomized, multicenter trial, Staudinger et al investigated the impact of prophylactic, continuous, lateral-rotation therapy on the prevalence of ventilator-associated pneumonia (VAP), the duration of mechanical ventilation, the length of hospital stay, and the mortality in critically ill medical patients. Results showed VAP frequency decreased during the ICU stay in the rotation group (11%) as compared with the control group (23%). Duration of ventilation (8±5 vs 14±23 d) and length of stay (25±22 d vs 39 ±45 d) were significantly shorter in the rotation group. Intolerance to lateral rotation was observed during the weaning phase in 29 (39%) of patients. Mortality was comparable between the groups.[15]
Studies comparing H2 receptor blockers with sucralfate have shown conflicting results, with a trend toward a reduction of ventilator-associated pneumonia (VAP) with the use of sucralfate.[16, 17, 18] These benefits were most notable with late-onset VAP. Use of sucralfate is also associated with a 4% increase in clinically significant bleeding. Proton pump inhibitors also may be used to prevent stress-related gastrointestinal bleeding.
Measures should be taken to prevent deep venous thrombosis. The selection for the method of deep venous thrombosis prevention should be based on individual patient characteristics and comorbid illnesses. Heparin, low-molecular-weight heparin, and compression stockings are means to help prevent deep venous thrombosis.
Rinses with oral chlorhexidine help prevent ICU-acquired hospital-acquired pneumonia (HAP) in patients undergoing coronary artery bypass procedures.[19] However, in a randomized controlled trial in 417 ICU patients, Panchabhai et al found that twice-daily oropharyngeal cleansing with 0.2% chlorhexidine solution had no prophylactic benefit for nosocomial pneumonia. Pneumonia developed in 7.1% of patients receiving chlorhexidine cleansing, compared with 7.7% of those in the control group, who received 0.01% potassium permanganate solution. Among patients who developed pneumonia, no significant difference was noted between the study group and the control group in the median day of development of pneumonia, median ICU stay, or mortality.[20]
A history of antibiotic use prior to the onset of ventilator-associated pneumonia (VAP) increases the probability of infection with multidrug-resistant (MDR) pathogens.
Alteration of the florae in the digestive tract due to oral or systemic antibiotics (ie, selective decontamination of the digestive tract) effectively reduces the incidence of ICU-acquired HAP in ICUs where the levels of antibiotic resistance are low. However, routine use of this approach is not recommended.
The differential diagnosis of nosocomial pneumonia includes the following:
Routine blood tests should be obtained to evaluate the patient for infection (white blood cell count) and to assess the patient's baseline renal and hepatic function for dosing of antibiotics. Blood cultures should also be obtained.
Samples of respiratory secretions from the distal respiratory tract with either bronchoscopic or nonbronchoscopic tests should be considered. Examples of these tests are blind bronchoalveolar lavage (BAL), bronchoscopic BAL, bronchoscopy-guided protected-specimen brush (PSB) sampling, and blind PSB sampling. Quantitative bacterial cultures are generally recommended to increase the reliability of these respiratory sampling techniques. The authors of this article prefer to use the bronchoscopy-guided techniques.
New markers such as procalcitonin and triggering receptors expressed on myeloid cells (TREM-1) are being evaluated.
In the ICU, portable chest radiography is commonly used in the diagnosis of ventilator-associated pneumonia (VAP). No single radiographic sign has diagnostic accuracy better than 68%. Air bronchograms are probably the best predictor of VAP. Among patients in the ICU, many infectious and noninfectious processes may cause the radiologic appearance of infiltrates. The absence of a radiologic infiltrate is helpful in excluding the diagnosis of VAP.
Chest CT scanning can be performed to evaluate the patient for underlying lung parenchyma disease, pleural effusions, and attenuation of consolidations.
Ultrasonography of the chest may be obtained to aid in the evaluation of pleural effusions and to guide sampling or drainage of the pleural fluid.
To evaluate bacteriologic evidence of pulmonary infection, samples of respiratory secretions may be obtained from the proximal and/or distal airways by using bronchoscopic or nonbronchoscopic techniques.
Some authorities suggest that bacteremia and/or positive cultures of pleural fluid help in identifying etiologic pathogens. For this reason, 2 sets of blood cultures are recommended. If a sufficient amount of pleural fluid is present to allow the effusion to be safely obtained for diagnostic tests, the pleural effusion should be sampled. The general recommendation is to perform a diagnostic thoracentesis under ultrasound guidance for mechanically ventilated patients.
Qualitative endotracheal aspirates are easy to obtain but have a high false-positive rate in ICU patients because of airway colonization. When quantitative endotracheal-aspirate cultures are used, a cutoff value of 106 is the most accurate, with a sensitivity of 38-82% and a specificity of 72-85%. However, when this cutoff is used, approximately 33% of patients with ventilator-associated pneumonia (VAP) may be missed. Only 40% of endotracheal-aspirate cultures coincide with results of protected brush sampling. Therefore, adjusting antibiotics on the basis of findings from endotracheal aspirates may lead to inadequate coverage of the causative pathogens.
Distal airway samples may be obtained by using bronchoscopic or nonbronchoscopic techniques. With nonbronchoscopic techniques, a catheter is blindly advanced through the endotracheal tube or tracheostomy and wedged in the distal airway. Various sampling methods include blind bronchial suction (BBS), blind bronchoalveolar lavage (BAL), and blind protected-specimen brush (PSB) sampling. Their sensitivities and specificities, respectively, are as follows[21] :
When nonbronchoscopic techniques are used, the diagnostic threshold may vary according to the method used. Cultures tend to be above the diagnostic threshold with bronchoscopic procedures more often than they are with nonbronchoscopic procedures.
For bronchoscopic sampling of the distal airway, a bronchoscopist must be available. Bronchoscopy is performed, and specimens are retrieved from specific areas of the bronchial tree. Regions to be sampled are determined from imaging studies, areas of maximal bronchial abnormality, or dependent airway segments.
The techniques are usually BAL and PSB sampling. With BAL, an aliquot of at least 120-250 mL of nonbacteriostatic sodium chloride solution is introduced through the wedged bronchoscope. When BAL is adequately performed, approximately 1 million alveoli are sampled.
As with any sampling procedure, proper technique is imperative to obtain reliable results. Because contamination from the oropharynx inevitably occurs during BAL, quantitative thresholds of less than 104 colony-forming units (cfu)/mL are generally considered contaminants, whereas those in the range of 105 -106 cfu are considered true pathogens.
With the bronchoscopic PSB method, the distal airway is sampled by telescoping the brush out of a sheath with a protective cap. When adequately performed, the sensitivity and specificity of bronchoscopic PSB sampling are approximately 89% and 94%, respectively. Because the clinician can retrieve 0.001- to 0.01-mL secretions (diluted in 1 mL of sodium chloride solution), a threshold of 103 represents a sample of 105 -106 cfu/mL.
Sensitivities and specificities of bronchoscopic BAL and PSB sampling, respectively, are as follows[22] :
Thoracentesis may be indicated to determine whether or not the pleural space is infected. Additionally, when the etiology of the pulmonary infiltrates remains unclear, procedures such as video-assisted thoracotomy or an open lung biopsy may be required to establish a diagnosis. Lung biopsy has been tolerated well, even in patients with adult respiratory distress syndrome. The authors' bias is to achieve early diagnosis before further clinical deterioration occurs.
Patients with severe hospital-acquired pneumonia (HAP) or health care–acquired pneumonia who require mechanical ventilatory support should be treated in a fashion similar to that of patients with ventilator-associated pneumonia (VAP).
Ventilator-associated tracheobronchitis (VAT) is an intermediate condition between airway colonization and VAP.[23] A study of ICU patients found that although VAT is less common than VAP, it had a similar incidence and frequently progressed to VAP. Patients diagnosed with VAT had similar outcomes to those with VAP, meaning antimicrobial therapy is appropriate.
For patients with early-onset VAP and no risk factors for multidrug-resistant (MDR) pathogens, currently recommended initial empiric antibiotics include 1 of the following options:
For patients with VAP and risk factors for MDR pathogens or for patients with late-onset VAP, initial antibiotic therapy may consist of 1 of the following options:
If infection with Legionella pneumophila is suspected, the regimen should include a macrolide or fluoroquinolone rather than an aminoglycoside.
Outcomes after VAP improve with the early administration of appropriate antibiotic regimens and with adequate dosing of antibiotics.
Antibiotics should be further adjusted on the basis of culture results. The first antibiotic regimen should be optimized, because inappropriate initial therapy is associated with worsened outcomes, even if the regimen is subsequently changed on the basis of the microbiologic results.
The 10 clinical caveats in selecting an empiric antibiotic regimen are as follows:
Antibiotic selection in trauma is similar. The prevalence of early VAP (defined as =4 d) due to MRSA in patients with multiorgan trauma is low even in communities with a high incidence of community-acquired MRSA.[24] Thus, coverage for MRSA in early VAP in a patient with multiorgan trauma is not necessary unless the patient has identified risk factors. Patients with multiorgan trauma who develop late VAP (defined as >4 d) are at a higher risk for MSRA pneumonia and should be treated accordingly. Antibiotics can be de-escalated based on culture results.
Clinicians should be aware of the local antibiotic resistance pattern in order to adequately begin an empiric antibiotic regimen. Other important factors are an adequate dose, the route of administration, and an understanding of the pharmacodynamic properties of particular antibiotics.
Beta-lactam antibiotics achieve less than 50% of the serum concentration in the lung, whereas fluoroquinolones and linezolid are found in comparable concentrations in bronchial secretions.
Aminoglycosides and quinolones are bactericidal in a concentration-dependent manner. In comparison, agents such as vancomycin and beta-lactams are bactericidal in a time-dependent fashion; that is, their bactericidal activity depends on the time the serum concentration is above the minimal inhibitory concentration for the target organism.
A postantibiotic effect is the ability of an antibiotic agent to suppress bacterial growth even after its levels decrease below the minimal inhibitory concentration for the organism.
When used to treat gram-negative bacilli, aminoglycosides and fluoroquinolones have a prolonged postantibiotic effect. On the contrary, beta-lactam antibiotics have a short postantibiotic effect against these organisms.
An understanding of the principles described above helps in adjusting intervals and doses of antibiotics. For example, aminoglycosides and quinolones are administered less often than other drugs and with doses that maximize initial serum concentrations. Aminoglycosides have been dosed by combining an entire day's therapy into a single dose. This type of dosing regimen takes advantage of the postantibiotic effect of the agent and its concentration-dependent killing ability.
Siempos et al conducted a meta-analysis of 5 randomized, controlled trials comparing probiotics and control on the incidence of VAP, and the results showed that administration of probiotics, compared with control, was beneficial in terms of incidence of VAP, length of ICU stay, and colonization of the respiratory tract with P aeruginosa. No difference was found between comparators for ICU mortality, in-hospital mortality, mechanical ventilation duration, and diarrhea. The authors suggest that probiotic administration may be associated with a lower incidence of VAP than control.[25]
According to Morrow et al, microbiologically confirmed VAP was significantly less likely to develop in patients on mechanical ventilation who were treated with the probiotic Lactobacillus rhamnosus GG than in those given placebo (40 vs 19.1%). They also found that patients treated with the probiotic had fewer days of antibiotics prescribed for VAP and for Clostridium difficile-associated diarrhea.[26]
Treatment failure may occur in 30% of patients who develop VAP, resulting in adverse outcomes. Therefore, patients should be closely monitored for therapy failure. Causes of treatment failure include the following: