1. 
   

   What are common mimickers of hospital-acquired pneumonia (HAP)?

   
   
2. 
   

   Is an invasive sampling procedure necessary for accurate diagnosis?

   
   
3. 
   

   Which pathogens typically cause HAP?

   
   
4. 
   

   Which antibiotics are indicated for treatment?

   
   
5. 
   

   For how long should patients be treated?

   
   
6. 
   

   What can be done to prevent HAP?

More than 100 years ago, Sir William Osler noted the frequent mismatch between clinical and postmortem diagnoses of pneumonia. The disparity ran both ways: clinicians overdiagnosed the disease in patients without pneumonia, and failed to diagnose it in patients with demonstrable pneumonia at autopsy. Despite profound advances in the tools available to clinicians, including computed tomography scans, bronchoscopy, and advanced microbiological diagnostics, the diagnosis of hospital-acquired pneumonia (HAP), or pneumonia acquired more than 48 hours after hospital admission, continues to be elusive, partly because it has many mimickers, and partly because the population at risk tends to be very complex.

Misdiagnosis has three serious consequences: failure to treat truly infected patients early is associated with increased mortality, inappropriate use of antibiotics in uninfected patients needlessly promotes antibiotic resistant organisms including Clostridium difficile, and premature diagnostic closure delays detection and treatment of the patient’s true cause of deterioration. Growing attention from legislators and quality improvement advocates has compounded the importance of accurate diagnosis. Some states now require hospitals to publicly report rates of ventilator-associated pneumonia (VAP), and some insurers have threatened to stop reimbursing hospitals for extra costs incurred due to VAP.

Health care–associated pneumonia is defined as pneumonia in a patient who has received health care as follows:

• Hospitalization in an acute care hospital for 2 or more days within 90 days of the infection
  
• Residence in a nursing home or long-term care facility
  
• Administration of intravenous antibiotics, chemotherapy, or wound care within the past 30 days
  
• Treatment with hemodialysis or attendance at a hospital-based clinic

These patients may present as outpatients, as general medical inpatients, or as ventilated patients in the intensive care unit. Although this chapter focuses primarily on VAP, since mechanically ventilated patients are at greater risk and better studied than other populations, the principles developed here are broadly applicable to all patients with health care–associated pneumonia.

Reported VAP rates have dropped dramatically over the past 20 years. Older literature reported VAP in 10% to 15% of ventilated patients, but more recent series report VAP in 5% or fewer of ventilated patients. The risk of VAP is primarily related to the duration of mechanical ventilation. Consequently, the risk of VAP is highest in burn and trauma units where mechanical ventilation tends to be prolonged (10.7 and 9.3 VAPs per 1000 ventilator-days in burn and trauma units, respectively), and lowest in units with fewer ventilator days per patient (2.5 VAPs per 1000 ventilator-days in medical and coronary units). On meta-analysis, an episode of VAP appears to extend intensive care length of stay by about 6 days, and doubles the risk of dying. The attributable cost of VAP is approximately $10,000 per episode.

The histological hallmark of HAP is heterogeneity. The lungs of ventilated patients tend to have multiple patchy areas of inflammation and infection, in various stages of recovery and progression. Cultures of these different areas often yield different organisms. These findings reveal the pathophysiology of HAP: patients tend to repeatedly aspirate small amounts of secretions into their lungs that either spontaneously heal, or progress to clinically manifest infection. In intubated patients, organisms enter the lungs through leakage around the endotracheal tube cuff. Processes that increase the risk of aspiration increase the risk of HAP. These include sedation, delirium, impaired consciousness, intubation, vomiting, and abnormal swallowing. Proton pump inhibitors are also associated with an increased risk of pneumonia, presumably because they facilitate greater microbial colonization of the upper gastrointestinal tract.

Causative organisms mirror the ecology of the mouth. The causative agents of HAP vary according to how long patients have been hospitalized. Early infections tend to be caused by the same organisms that cause community acquired pneumonia, namely Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and respiratory viruses such as influenza. Later infections are typically caused by Staphylococcus aureus and gram-negative organisms such as Pseudomonas, Klebsiella, Enterobacter, Acinetobacter. The longer patients remain in hospital, the greater the risk of colonization and infection with multidrug-resistant bacteria, including methicillin-resistant S aureus, extended spectrum beta-lactamase–resistant gram negatives, and carbapenem-resistant enterobacteraciae.

There are no pathognomonic findings of VAP. The cardinal signs sought by clinicians (fever, hypoxemia, purulent sputum, leukocytosis, and new radiographic infiltrates) are all insensitive, with positive and negative likelihood ratios near one (Table 194-1). Even when present in combination, these signs have a low positive likelihood ratio.

The limited diagnostic value of these signs is due to the complexity of the patient population at risk for VAP. Hospitalized patients in general and ventilated patients in particular tend to be at risk for a wide array of complications superimposed upon underlying conditions and presenting illnesses. As such, each of the signs sought in the diagnosis of pneumonia has a broad differential diagnosis, including non-infectious aspiration pneumonitis, thromboembolic disease, sepsis, atelectasis, pulmonary edema, hemorrhage, contusion, and acute respiratory distress syndrome. Typically, only about a third of patients with the clinical syndrome of VAP (fever, purulent sputum, leukocytosis, and a new infiltrate) are confirmed to have pneumonia if they undergo intensive investigation or autopsy. Instead, two or more alternative processes are often present that alone or in combination mimic the clinical picture of VAP (for example, atelectasis and line sepsis).

Laboratory analysis of pulmonary secretions is critical to aid diagnosis and guide treatment, but considerable judgment is still required to make sense of microbiology results, as their predictive power is nuanced (Table 194-2). False-positive and false-negative cultures are common. False-positive cultures usually reflect contamination of the specimen with oral or endotracheal tube colonizers. False-negative cultures are due to sampling an uninfected lung segment, inhibition of bacterial growth by prior antibiotic exposure, or failure to cross an arbitrarily set quantitative growth threshold.

The absence of neutrophils in bronchoalveolar lavage (BAL) fluid helps rule out VAP, but their presence is not diagnostic. By extension, a sputum Gram stain with few or no neutrophils probably makes HAP very unlikely. Visualizing organisms on a BAL Gram stain is suggestive of VAP, and can provide clues about etiology. Organisms on Gram stain from blind bronchial aspirates are less reliable, since these specimens are more prone to contamination. As cultures tend to magnify small amounts of contamination, the converse is true when looking at quantitative culture data. Positive cultures from BAL specimens, which have relatively low growth thresholds for positivity, are often contaminants, but exuberant growth from a bronchial aspirate, which has a high growth threshold for positivity, is predictive of VAP, presumably because bona fide disease has a very high bioburden that is able to outgrow bystander bacteria contaminating the specimen.

A large, multicenter randomized controlled trial comparing routine BAL to endotracheal aspirates to diagnose patients with suspected VAP confirmed the balance of pros and cons between invasive and noninvasive diagnostic methods described above. The trial found no difference in mortality, length of stay, appropriateness of antibiotic choices, or total amount of antibiotic usage between the two study arms. As such, bronchoscopy should be reserved for patients failing therapy guided by endotracheal aspirates.