(See also Overview of Pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more .)
Ventilator-associated pneumonia is pneumonia that develops at least 48 hours after endotracheal intubation or within 48 hours of extubation. Ventilator-associated pneumonia is a subset of hospital-acquired pneumonia, Hospital-Acquired Pneumonia Hospital-acquired pneumonia (HAP) develops at least 48 hours after hospital admission. The most common pathogens are gram-negative bacilli and Staphylococcus aureus; antibiotic-resistant... read more , which includes pneumonia in inpatients who are not receiving mechanical ventilation. Ventilator-associated pneumonia often involves more resistant pathogens and poorer outcomes than other forms of hospital-acquired pneumonia.
Etiology of Ventilator-Associated Pneumonia
The most common cause of ventilator-associated pneumonia is microaspiration of bacteria that colonize the oropharynx and upper airways in seriously ill patients.
Risk factors
Endotracheal intubation is the major risk factor for ventilator-associated pneumonia. Endotracheal intubation breaches airway defenses, impairs cough and mucociliary clearance, and facilitates microaspiration of bacteria-laden secretions that pool above the inflated endotracheal tube cuff. In addition, bacteria form a biofilm on and within the endotracheal tube that protects them from antibiotics and host defenses. The highest risk of ventilator-associated pneumonia occurs during the first 10 days after intubation. Ventilator-associated pneumonia occurs in 9 to 27% of mechanically ventilated patients (1 Etiology references Ventilator-associated pneumonia (VAP) develops at least 48 hours after endotracheal intubation. The most common pathogens are gram-negative bacilli and Staphylococcus aureus; antibiotic-resistant... read more ).
Pathogens
Pathogens and antibiotic resistance patterns vary significantly among institutions and can vary within institutions over short periods (eg, month to month). Local antibiograms at the institutional level that are updated on a regular basis are essential in determining appropriate empiric antibiotic therapy. In general, the most important pathogens are
Pseudomonas aeruginosa
Methicillin-sensitive Staphylococcus aureus
Methicillin-resistant S. aureus (MRSA)
Other important pathogens include enteric gram-negative bacteria (mainly Enterobacter species, Klebsiella pneumoniae, Escherichia coli, Serratia marcescens, Proteus species, and Acinetobacter species).
Methicillin-sensitive S. aureus, Streptococcus pneumoniae, and Haemophilus influenzae are most commonly implicated when pneumonia develops within 4 to 7 days of hospitalization, whereas P. aeruginosa, MRSA, and enteric gram-negative organisms become more common with increasing duration of intubation or hospitalization.
Prior IV antibiotic treatment (within the previous 90 days) greatly increases the likelihood of antibiotic-resistant organisms, particularly MRSA and Pseudomonas infection in ventilator-associated pneumonia (2 Etiology references Ventilator-associated pneumonia (VAP) develops at least 48 hours after endotracheal intubation. The most common pathogens are gram-negative bacilli and Staphylococcus aureus; antibiotic-resistant... read more ). Infection with a resistant organism markedly increases mortality and morbidity. Other risk factors for antibiotic-resistant organisms specific to ventilator-associated pneumonia include
Septic shock at time of ventilator-associated pneumonia
Acute respiratory distress syndrome (ARDS) preceding ventilator-associated pneumonia
Hospitalization for ≥ 5 days prior to the occurrence of ventilator-associated pneumonia
Acute renal replacement therapy prior to ventilator-associated pneumonia onset
High-dose corticosteroids increase the risk of Legionella and Pseudomonas infections. Chronic suppurative lung diseases such as cystic fibrosis Cystic Fibrosis Cystic fibrosis is an inherited disease of the exocrine glands affecting primarily the gastrointestinal and respiratory systems. It leads to chronic lung disease, exocrine pancreatic insufficiency... read more and bronchiectasis Bronchiectasis Bronchiectasis is dilation and destruction of larger bronchi caused by chronic infection and inflammation. Common causes are cystic fibrosis, immune defects, and recurrent infections, though... read more increase the risk of gram-negative pathogens, including antibiotic-resistant strains.
Etiology references
1. Reignier J, Mercier E, Le Gouge A, et al: Effect of not monitoring residual gastric volume on risk of ventilator-associated pneumonia in adults receiving mechanical ventilation and early enteral feeding: a randomized controlled trial. JAMA 309(3):249–256, 2013. doi:10.1001/jama.2012.196377
2. Kalil AC, Metersky ML, Klompas M, et al: Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 63(5):e61–111, 2016.
Symptoms and Signs of Ventilator-Associated Pneumonia
Pneumonia in critically ill, mechanically ventilated patients typically causes fever and increased respiratory rate or heart rate or changes in respiratory parameters, such as an increase in purulent secretions or worsening hypoxemia.
Diagnosis of Ventilator-Associated Pneumonia
Chest x-ray and clinical criteria (limited accuracy)
Sometimes bronchoscopy or blood cultures
Diagnosis is imperfect. In practice, ventilator-associated pneumonia is often suspected on the basis of the appearance of a new infiltrate on a chest x-ray that is taken for evaluation of new symptoms or signs (eg, fever, increased secretions, worsening hypoxemia) or of leukocytosis. However, no symptom, sign, or x-ray finding is sensitive or specific for the diagnosis, because all can be caused by atelectasis Atelectasis Atelectasis is collapse of lung tissue with loss of volume. Patients may have dyspnea or respiratory failure if atelectasis is extensive. They may also develop pneumonia. Atelectasis is usually... read more , pulmonary embolism Atelectasis Atelectasis is collapse of lung tissue with loss of volume. Patients may have dyspnea or respiratory failure if atelectasis is extensive. They may also develop pneumonia. Atelectasis is usually... read more , or pulmonary edema Pulmonary Edema Pulmonary edema is acute, severe left ventricular failure with pulmonary venous hypertension and alveolar flooding. Findings are severe dyspnea, diaphoresis, wheezing, and sometimes blood-tinged... read more and may be part of the clinical findings in acute respiratory distress syndrome Acute Hypoxemic Respiratory Failure (AHRF, ARDS) Acute hypoxemic respiratory failure is defined as severe hypoxemia (PaO2 (See also Overview of Mechanical Ventilation.) Airspace filling in acute hypoxemic respiratory failure (AHRF) may result... read more .
Gram stain and semiquantitative cultures of endotracheal aspirates, though not definitive for identifying infection, are recommended for guiding treatment in ventilator-associated pneumonia. Bronchoscopic sampling of lower airway secretions for quantitative culture yields more reliable specimens that can differentiate colonization from infection. Information gained from bronchoscopic sampling reduces antibiotic use and assists in switching from broader to narrower antibiotic coverage. However, it has not been shown to improve outcomes.
Measurement of inflammatory mediators in bronchoalveolar lavage fluid or serum has not been shown to be reliable in deciding on initiation of antibiotics. The only finding that reliably identifies both pneumonia and the responsible organism is a pleural fluid culture (obtained via thoracentesis in a patient with pleural effusion) that is positive for a respiratory pathogen.
Blood cultures are also relatively specific if a respiratory pathogen is identified but are insensitive.
Treatment of Ventilator-Associated Pneumonia
Empirically chosen antibiotics active against resistant organisms
If ventilator-associated pneumonia is suspected, treatment is with antibiotics that are chosen empirically based on
Local sensitivity patterns
Patient risk factors for antibiotic-resistant pathogens
Prior microbiology results from patient samples demonstrating colonization with antibiotic-resistant pathogens
In the 2007 guidelines, the Infectious Diseases Society of America and the American Thoracic Society used very broad criteria for defining the population at risk of infection with antibiotic-resistant pathogens, which resulted in the majority of patients with ventilator-associated pneumonia VAP requiring broad-spectrum antibiotic therapy for MRSA and resistant Pseudomonas. The 2016 guidelines of the Infectious Diseases Society of America and the American Thoracic Society emphasize use of a narrower spectrum of empiric antibiotics when possible (1 Treatment reference Hospital-acquired pneumonia (HAP) develops at least 48 hours after hospital admission. The most common pathogens are gram-negative bacilli and Staphylococcus aureus; antibiotic-resistant... read more ). Empiric therapy for ventilator-associated pneumonia without risk factors for antibiotic-resistant organisms Antibiotic Resistance Antibacterial drugs are derived from bacteria or molds or are synthesized de novo. Technically, “antibiotic” refers only to antimicrobials derived from bacteria or molds but is often (including... read more and high mortality (mechanical ventilation for pneumonia or septic shock), in an institution where MRSA incidence is < 10% to 20% (of S. aureus isolates) and P. aeruginosa resistance is < 10% for commonly used empiric antipseudomonal antibiotics, could include any one of the following:
Piperacillin/tazobactam
Cefepime
Levofloxacin
Imipenem
Meropenem
In treatment settings where MRSA rates are > 10% to 20%, vancomycin or linezolid should be added. In patients who are at high risk for mortality or who have risk factors for antibiotic-resistant organisms, or in the absence of reliable local antibiograms, recommendations include triple therapy using 2 drugs with activity against Pseudomonas and 1 drug with activity against MRSA:
An antipseudomonal cephalosporin (cefepime or ceftazidime) or an antipseudomonal carbapenem (imipenem, meropenem) or a beta-lactam/beta-lactamase inhibitor (piperacillin/tazobactam)
An antipseudomonal fluoroquinolone (ciprofloxacin or levofloxacin) or an aminoglycoside (amikacin, gentamicin, tobramycin)
Linezolid or vancomycin
While indiscriminate use of antibiotics is a major contributor to development of antimicrobial resistance, adequacy of initial empiric antibiotics is a major determinant of a favorable outcome. Therefore, treatment must begin with initial use of broad-spectrum drugs. Patients should be reassessed 2 to 3 days after initiation of treatment, and antibiotics are then changed to the narrowest regimen possible based on clinical response and the results of cultures and antibiotic susceptibility testing.
Treatment reference
1. Kalil AC, Metersky ML, Klompas M, et al: Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 63(5):e61–111, 2016.
Prognosis for Ventilator-Associated Pneumonia
The mortality in ventilator-associated pneumonia is high despite the availability of effective antibiotics. However, not all mortality is attributable to the pneumonia itself; many of the deaths are related to the patient's comorbidities. Adequacy of initial antimicrobial therapy clearly improves prognosis. Infection with antibiotic-resistant bacteria worsens prognosis.
Prevention of Ventilator-Associated Pneumonia
There are a number of measures that can help prevent ventilator-associated pneumonia. Semiupright or upright positioning reduces risk of aspiration and pneumonia compared with recumbent positioning and is the simplest and most effective preventive method. Noninvasive ventilation using continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BPAP) prevents the breach in airway defense that occurs with endotracheal intubation and eliminates the need for intubation in some patients, and has been associated with a reduced incidence of ventilator associated pneumonia.
Continuous aspiration of subglottic secretions using a specially designed endotracheal tube attached to a suction device reduces the risk of microaspiration and the incidence of ventilator-associated pneumonia; however, overall clinical outcomes are not altered. Silver-coated endotracheal tubes reduce biofilm formation and the incidence of ventilator-associated pneumonia; however, overall clinical outcomes are not altered.
Selective decontamination of the oropharynx (using topical gentamicin, colistin, chlorhexidine, vancomycin cream, or a combination) or of the entire gastrointestinal tract (using polymyxin B, an aminoglycoside or quinolone, and either nystatin or amphotericin B) is controversial because of concerns about resistant strains and because decontamination, although it decreases incidence of ventilator-associated pneumonia, has not been shown to decrease mortality.
Surveillance cultures and routinely changing ventilator circuits or endotracheal tubes have not been shown to decrease ventilator-associated pneumonia.
Key Points
Ventilator-associated pneumonia is pneumonia that develops at least 48 hours after endotracheal intubation.
Likely pathogens differ from those causing community-acquired pneumonia and often require initial empiric antibiotic therapy that is active against antibiotic-resistant organisms.
Diagnosis is difficult, with culture of a potential pathogen from pleural fluid or blood being the most specific finding.
Reassess patients 2 to 3 days after initiation of treatment, and change antibiotics based on available culture and clinical data.