Patients with hospital-acquired pneumonia (HAP) are those who develop pneumonia 48 hours or more after hospital admission. Ventilator-associated pneumonia (VAP) is defined as pneumonia developed after 48 hours of endotracheal intubation, and is believed to affect approximately 10% of patients who undergo mechanical ventilation for longer than 48 hours. Together, these illnesses are the most frequent hospital-acquired infections and are associated with significant morbidity and mortality. Diagnosis of HAP/VAP can be difficult because its symptoms, such as fever and increased white blood cell count, are associated with a variety of conditions in hospitalized patients; in addition, differentiating between airway colonization and infection can be challenging. Although there is no gold standard for diagnosis, laboratory testing for HAP and VAP typically includes CBC, gram stain and culture, and arterial blood gas or oximetry. Molecular tests such as multiplex polymerase chain reaction (PCR) panels and next generation sequencing (NGS) are rapidly developing technologies that may contribute to diagnosis and to identification of treatment-resistant pathogens. Given the emergence of multidrug-resistant (MDR) organisms, accurate pathogen identification and treatment in HAP/VAP have become increasingly important. In addition, because pneumonia can be caused by bacteria, viruses, or fungi, pathogen determination will affect patient treatment and management.
Quick Answers for Clinicians
CBC, gram stain, and culture of respiratory specimens are primary tests for diagnosis of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP); arterial blood gas analysis/oximetry is also indicated. Blood cultures have limited use in patients with suspected HAP/VAP, but are recommended to help guide clinical decision-making in cases of bacteremic illness. Nucleic-acid amplification tests, including multiplex panels, are able to rapidly identify pathogens, and may include detection of antimicrobial resistance genes to help guide treatment. Next generation sequencing (NGS) is an emerging technology that holds promise in identifying pathogens without requiring advance knowledge of those likely to be involved.
C-reactive protein (CRP) and soluble triggering receptor expressed on myeloid cells (sTREM-1) tests have been suggested to aid in hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) diagnosis and clinical decision-making, but current data and the most recent guidelines do not support their use. Procalcitonin (PCT) concentrations, although not recommended for diagnosis or initiation of antibiotics, may be useful to help determine when to discontinue antibiotic therapy. Testing to target optimal antibiotic blood concentrations (pharmacokinetic/pharmacodynamic-optimized dosing) may be helpful to guide treatment, depending on the antibiotic used.
Common pathogens associated with ventilator-associated pneumonia (VAP) include Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacter species. Some of the most common organisms implicated in hospital-acquired pneumonia (HAP) include Streptococcus pneumoniae, S. aureus, and enteric gram-negative bacilli such as P. aeruginosa, Klebsiella pneumoniae, Enterococcus coli, and Enterobacter species. Common multidrug-resistant (MDR) pathogens associated with HAP include MDR Pseudomonas, methicillin-resistant S. aureus (MRSA), and extended spectrum beta (β)-lactamase (EBSL)-generating gram-negative bacteria. Organisms that less commonly cause HAP include Mycobacterium tuberculosis, nontuberculous mycobacteria, Chlamydophila species, Coxiella, and fungi (eg, Aspergillus, Blastomyces, Coccidioides). Specific patient risk factors such as immunosuppression and travel history may raise suspicion for these pathogens. It should be noted that organisms associated with community-acquired pneumonia, such as Mycoplasma pneumonia, can differ from those most common in HAP/VAP. See Community-Acquired Pneumonia topic for additional information.
Previous treatment with intravenous antibiotics is a risk factor for hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) infection with multidrug-resistant (MDR) pathogens, including MDR Pseudomonas and methicillin-resistant Staphylococcus aureus (MRSA). Additional risk factors for MDR pathogens in VAP, in particular, include septic shock at the time of VAP, acute respiratory distress syndrome or dialysis preceding VAP onset, and ≥5 days of hospitalization before onset.
Indications for Testing
Laboratory testing for HAP/VAP is appropriate for:
- Diagnosis in hospitalized patients or patients receiving mechanical ventilation with new-onset fever, purulent sputum, leukocytosis, and/or decline in oxygenation
- Monitoring to guide treatment decisions in patients diagnosed with HAP/VAP (see Monitoring below)
Criteria for Diagnosis
|Presence of infiltrate, plus clinical evidence of infectious origin of infiltrate (new onset of fever, purulent sputum, leukocytosis, decline in oxygenation)||Pneumonia occurring >48 hrs after admission (not due to progression of disease present at admission)a; not associated with mechanical ventilation||Pneumonia occurring >48 hrs after endotracheal intubation|
|aClinical criteria are recommended for diagnosis of HAP/VAP, as opposed to clinical criteria in conjunction with serum procalcitonin, sTREM-1, CRP, or Clinical Pulmonary Infection Score.
CRP, C-reactive protein; sTREM-1, soluble triggering receptor expressed on myeloid cells
Gram Stain and Culture
Culture of respiratory secretions is a primary test for HAP/VAP diagnosis and is also best performed near the point of care. Guidelines recommend a noninvasive collection method such as endotracheal aspiration and semiquantitative rather than quantitative culture for patients with suspected VAP. Invasive methods such as bronchoalveolar lavage (BAL), protected specimen brush (PSB), and blind bronchial sampling are discouraged due to increased risk.
Noninvasive collection is also recommended in patients with suspected HAP, when possible. It may be necessary to induce sputum, and nasotracheal suction or endotracheal aspiration may be required if the patient is unable to produce sputum or was recently placed on mechanical ventilation.
Blood cultures are minimally invasive and inexpensive, low risk, and can detect sepsis. Data to support the use of blood cultures in patients with suspected HAP/VAP are limited. However, in some patients with bacteremic illness, the identification of a particular pathogen may guide clinical decision-making; therefore, current guidelines still recommend blood cultures be obtained in cases of suspected HAP and VAP.
Some additional tests have been proposed for HAP/VAP diagnosis, but current data are insufficient to support their use. Tests for procalcitonin (PCT) concentration and sTREM-1 are still being studied to evaluate their role in diagnosis. Some reports suggest that CRP testing may help to determine whether to begin antibiotic treatment. However, none of these tests are recommended in the current guidelines.
The role of multiplex molecular tests, such as PCR panels (also called syndromic panels) and NGS, is yet to be determined. As such, they are not yet recommended in guidelines for HAP/VAP testing. These tests show promise in their ability to identify a range of pathogens and potentially help guide treatment decisions. However, targeted PCR-based tests are generally more sensitive and are preferred when specific pathogens are suspected.
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