Ventilator-Associated Pneumonia

Updated: Dec 29, 2022
  • Author: Shakeel Amanullah, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
  • Print

Practice Essentials

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. [1] 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 in nonventilated patients. [1]

Together, VAP and HAP are the most common nosocomial infection, accounting for an estimated 22% of of hospital acquired infections. [2] Approximately 10% of patients who required mechanical ventilation acquire VAP. [3] VAP extended the time on mechanical ventilation and duration of hospitalization, with a resulting increases in cost of care.

In 2016, the American Thoracic Society (ATS) and the Infectious Disease Society of America (IDSA) updated guidelines for the management of HAP and ventilator-associated pneumonia (VAP). VAP is no longer a subtype of HAP as in previous guidelines. HAP and VAP are now viewed as distinct entities. VAP is further divided into multidrug resistant (MDR) VAP and non-MDR VAP. [4]

Exposure to intravenous antibiotics within 90 days is a predisposing factor to MDR-VAP. [5] Other risk factors include septic shock, acute respiratory virus syndrome (ARDS), and acute renal replacement therapy. In addition, patients who develop VAP after longer than 5 days of hospitalization are at higher risk of infection with MDR organisms than patients who develop VAP earlier in their hospitalization. [5] Coma upon ICU admission offers a protective effective against MDR VAP. [4]

More recently, the advent of coronavirus disease 2019 (COVID-19) has seen an associated increased risk of VAP that is not entirely related to the duration of ventilatory support. [6, 7]  Potential factors for this heightened risk may include less strict adherence to standard prevention strategies early in the pandemic, impaired disease- and therapy-associated immune function, prolonged sedation, more frequent need for prone ventilation, and an increased risk for pulmonary infarction and related superinfection. [6] Moreover, patients with COVID-19 and VAP have significantly higher rates of shock and bloodstrream and polymicrobial infections. [8]

For other discussions on pneumonia, see the following Medscape Drugs & Diseases topics:

Next:

Epidemiology of VAP

Ventilator-associated pneumonia (VAP) is a complication in approximately 7-32% of healthcare-associated infections, [1] 10% of children with device-related infections, [1] and 10% of patients who receive mechanical ventilation. [3]  It also is the second most common hospital-acquired infection in pediatric and neonatal intensive care units (PICUs; NICUs). [1]  

The incidence of VAP increases with the duration of mechanical ventilation. The attributable mortality has been estimated at 13%. [9] 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.

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.

Previous
Next:

Clinical Presentation of VAP

Patient history

The patient's medical history should include an assessment for risk factors related to multidrug-resistant (MDR) pathogens. Such risk factors include the following:

  • Current hospitalization admission of greater than 5 days

  • Hospital admission more than 2 days in the preceding 90 days

  • Antibiotic use in the previous 90 days

  • Residence in a nursing home or extended-care facility

  • Home infusion therapy and wound care

  • Long-term dialysis within 30 days

  • Immunocompromise

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.

Previous
Next:

Laboratory Studies

Because of the growing frequency of multidrug-resistant ventilator-associated pneumonia (VAP), as well as the risks of initial ineffective therapy, the American Thoracic Society (ATS) and the Infectious Disease Society of America (IDSA) recommend cultures of respiratory secretions should be obtained from all patients with suspected VAP. [4]

For patients with suspected hospital-associated (HAP)/VAP, the IDSA strongly recommends using clinical criteria alone to make the diagnosis. Biomarkers, such as procalcitonin, soluble triggering receptor expressed on myeloid cells (obtained via bronchoalveolar lavage), or C-reactive protein combined with clinical criteria should not be used to diagnose HAP/VAP or in the decision to initiate antibiotic treatment. (IDSA practice guidelines 2016). The biomarker procalcitonin (PCT) is usually unhelpful in the diagnosis of nosocomial pneumonia in patients in the intensive care unit (ICU), who often have elevated PCT levels due to hypotension, renal failure, hepatic insufficiency, pancreatitis, drug reactions, or lung cancer. [10, 11] In addition, there is low sensitivity (67%) and specificity (83%) of clinical criteria plus PCT approach in diagnosing HAP or VAP. [12] Furthermore, even the use of the Modified Clinical Pulmonary Infection Score combined with clinical criteria should not be used to diagnose HAP/VAP. Clinical criteria alone is adequate to make the diagnosis.

The following is the recommended general laboratory approach by the IDSA/ATS. [4] Noninvasive sampling with semiquantitative culture can be performed much more rapidly, with fewer resources, and fewer complications compared to invasive sampling techniques. For patients with suspected pneumonia, antibiotic treatment can be discontinued if the quantitative culture results are below the diagnostic threshold, including the following:

  • Endotracheal aspirates: 1,000,000 colony forming units (CFUs)
  • Bronchoscopic or mini-BAL culture: 10,000 CFU/ml
  • Protected specimen brush (PSB): 1000 CFU/mL (Shebl and Gulick 2020)

Blood cultures should also be obtained. Approximately 15% of patients with VAP are bacteremic and a nonpulmonary source of bacteremia is identified in at least 25% of positive blood cultures. [4] Identification of a nonpulmonary source of infection will guide antibiotic selection as empiric VAP therapy may not be effective. [4]

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.

Previous
Next:

Imaging Studies

In the intensive care unit (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 computed tomography (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.

Previous
Next:

Procedures

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.

A meta-analysis found no evidence that the use of quantitative cultures of respiratory secretions results in lower mortality compared to qualitative cultures in patients with VAP. In addition, sampling technique did not affect any clinical outcome, including mean duration of mechanical ventilation, ICU length of stay, or mortality. [13] Based on a review of the evidence, the American Thoracic Society (ATS) and the Infectious Disease Society of America (IDSA) guidelines recommend noninvasive sampling by endotracheal aspiration with semiquantitative cultures to diagnose VAP, rather than quantitative cultures from either invasive (bronchoscopic) or noninvasive sampling. If invasive quantitative cultures are performed and results are below the diagnostic threshold for VAP, antibiotics should be withheld rather than continued. [4]

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.

Microbiologic approach to diagnosing ventilator-associated pneumonia

For patients with suspected VAP, sampling of the lower airways for quantitative cultures can be obtained through the following methods:

  • Blind tracheobronchial aspiration (TBAS) can be done by inserting a flexible catheter into the distal trachea; however, since it is blind sampling, there is no direct sampling of the lung in which radiographic evidence shows infiltrates. Furthermore, as the catheter is inserted through the endotracheal tube, there is a risk of contamination leading to false-positive results.
  • Bronchoscopy with bronchoalveolar lavage (BAL) allows for direct sampling of the lung segments with radiographic evidence of infiltrates. Limitations of the technique include operator-skill, contamination, and risk of worsening hypoxemia.
  • Protected specimen brush (PSB) can be advanced through a bronchoscope to avoid upper airway contamination. [5]
Previous
Next:

Treatment

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. ATS/IDSA guidelines recommend against antibiotic therapy. [4]

The ATS/IDSA guidelines recommend coverage for S aureus, P aeruginosa, and other gram-negative bacilli be included in all empiric regimens to treat suspected VAP. Empiric regimen selection should be guided by local antibiotic-resistance data and all hospitals should regularly generate an antibiogram specific to their location. Antibiotic treatment should be selected from one of the following groups [4] :

The guidelines noted that nonbeta-lactam-based aminoglycosides should be avoided effective alternative agents are available. Polymyxins should be reserved for settings with high prevalence of multidrug resistance and physicians with expertise in using this medication. [4]

Additional key treatment recommendations for suspected VAP include [4] :

  • Linezolid or vancomycin in patients with a risk factor for antimicrobial resistance or patients being treated in units where >10%–20% of S aureus isolates are methicillin resistant or the prevalence of MRSA is unknown.
  • Piperacillin-tazobactam, cefepime, levofloxacin, imipenem, or meropenem in patients without risk factors for antimicrobial resistance, who are being treated in ICUs where < 10%–20% of S aureus isolates are methicillin resistant.
  • Two antipseudomonal antibiotics from different classes only in patients with a risk factor for antimicrobial resistance, or patients in units where >10% of gram-negative isolates are resistant to an agent being considered for monotherapy, or patients in an ICU where local antimicrobial susceptibility is unknown.
  • Monotherapy with an agent active against P aeruginosa in patients without risk factors for antimicrobial resistance who are being treated in ICUs where ≤10% of gram-negative isolates are resistant to the agent being considered.

Recommendations for treatment when the pathogen is known include the following [4] :

  • P aeruginosa: antibiotic selection based on results of antimicrobial susceptibility testing; monotherapy preferred. If patient is in septic shock or at high risk of death, combination therapy using two antibiotics
  • Acinetobacter species: carbapenem or ampicillin/sulbactam; intravenous colistin or polymyxin B and adjunctive inhaled colistin for MDR isolates sensitive to polymyxin. Adjunctive rifampicin and use of tigecycline are not recommended.
  • Carbapenem-resistant pathogens: intravenous colistin or polymyxin B

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.

Clinical caveats in selecting an empiric antibiotic regimen are as follows:

  1. The administration of antibiotics should not be delayed for the sole purpose of performing diagnostic tests. If the clinical pretest probability for VAP is high, antibiotics should be started promptly regardless of whether the culture results are positive.

  2. If the patient received antibiotics in the recent past, the new antibiotic should be chosen from a class different from the previous ones to avoid selecting antibiotics to which the bacterial pathogen has become resistant.

  3. When an appropriate and adequate initial antibiotic regimen is started, every effort should be made to shorten the duration of antibiotic therapy. If a patient receives appropriate and adequate empiric antibiotic therapy, the duration of antibiotic treatment may be shortened from the traditional 14-21 days to 7 days if the etiologic organism is not P aeruginosa.

  4. False-negative culture results occur in patients who have been taking antibiotics for 24-72 hours before the collection of respiratory specimens. In these patients, using a BAL threshold 10-fold lower than usual may be helpful for avoiding false-negative results.

  5. Aerosolized antibiotics may be used as an adjunct to systemic antibiotics, although they have not been shown to be effective as sole therapy for VAP.

  6. Certain organisms, such as Escherichia coli, Klebsiella species, and Enterobacter species produce extended-spectrum beta-lactamase (ESBL), and screening tests for the production of ESBL should be performed. Carbapenems are generally effective against these ESBL-producing organisms.

Antibiotic selection in trauma is similar. The prevalence of early VAP (defined as = 4 days) due to MRSA in patients with multiorgan trauma is low even in communities with a high incidence of community-acquired MRSA. [14] 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 days) are at a higher risk for MSRA pneumonia and should be treated accordingly. Antibiotics can be de-escalated based on culture results.

Probiotics

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. [15]

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. [16]

Further inpatient care

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.

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:

  • Inadequate treatment in terms of the choice and dosage of antibiotics

  • Wrong diagnosis

  • Development of resistance with Pseudomonas, Enterobacter, or other species during treatment

  • Superinfection

  • Development of concomitant infection

  • Complications of VAP (eg, abscess, empyema)

Previous
Next:

Prevention

Intubation with mechanical ventilation increases the risk of pneumonia 3- to 21-fold [17, 18, 19, 20] and should be avoided if possible. Noninvasive positive-pressure ventilation is an option to consider, especially in the following groups:

  • Patients with exacerbations of chronic obstructive pulmonary disease

  • Patients with acute hypoxic respiratory failure

  • Patients with immunosuppression and respiratory failure

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 semirecumbent patients, [21] although there no difference in mortality. Placing patients in a semirecumbent position is associated with approximately a 3-fold reduction in the risk of hospital-acquired pneumonia (HAP), [21] 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. [22]

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. [23]

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. [24] 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.

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. [25, 26, 27] 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.

Rinses with oral chlorhexidine help prevent ICU-acquired hospital-acquired pneumonia (HAP) in patients undergoing coronary artery bypass procedures. [28] 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. [29]

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.

A multifaceted intervention including head-of-bed elevation, use of subglottic secretion drainage endotracheal tubes, oral care, chlorhexidine mouth care, and daily spontaneous awakening and breathing trials conducted in 56 ICUs resulted in a mean ventilator-associated event rate significantly decreased from 7.34 to 4.58 cases per 1,000 ventilator-days after 24 months of implementation (p = 0.007). During the same time period, infection-related ventilator-associated complication and possible and probable ventilator-associated pneumonia rates decreased from 3.15 to 1.56 and 1.41 to 0.31 cases per 1,000 ventilator-days (P=0.018, P=0.012), respectively. [30]

Previous