CONTENTS

• Basics
• Epidemiology & risk factors
• Stepwise general approach to HAP:
  • (1) Initial consideration for the possibility of HAP
  • (2) Consider CT scan
  • (3) Diagnosis & treatment of probable HAP
  • (4) Data review over 24-72 hours
  • (5) Ongoing management of HAP
• Other aspects of HAP management:
  • Approach to treatment failure
  • Bronchoscopy in HAP
• Questions & discussion

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basics

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definition of hospital-acquired pneumonia (HAP)

• HAP requires the following components:
  • (1) Pneumonia that develops after >48 hours in the hospital (early-onset pneumonias occurring <48 hours after admission are considered community-acquired pneumonia, since they were likely developing prior to admission).
  • (2) Patient has not been intubated for >48 hours (if so, this would be classified as a ventilator-acquired pneumonia (VAP)). (Murray 2022)
• HAP, CAP, and VAP are defined as mutually exclusive entities. (Murray 2022) Some articles refer to this HAP as “non-ventilator hospital acquired pneumonia” for the sake of clarity, but that's the same thing as HAP. 

hospital-acquired pneumonia is challenging

• HAP is very similar to ventilator-associated pneumonia (VAP). However, unlike VAP, HAP patients aren't intubated so it's often impossible to obtain a high-quality sputum sample. In the absence of sputum, evaluation can get very hazy.
• Compared to VAP, there is less data available regarding HAP. Our overall approach to HAP will be based on our approach to VAP (since this has been better defined and investigated).
• There is no gold-standard diagnostic test for HAP. This makes it exceedingly difficult to perform accurate research on HAP. Determining the sensitivity and specificity of any particular test for the diagnosis of HAP can be methodologically impossible because there is no gold-standard to compare different tests against.

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epidemiology & risk factors

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epidemiology

• HAP is 2-3 times more common than VAP. ~100,000 patients per year develop HAP in the United States.
• HAP may be the third-leading nosocomial infection (after gastrointestinal infection and surgical-site infection). (Murray 2022)

risk factors for HAP

• Acute events:
  • Acute stroke.
  • Surgery (especially involving the chest or upper abdomen, which impairs coughing).
• General risk factors:
  • COPD (may cause colonization of the airways with bacteria).
  • Higher severity of illness.
  • Greater burden of comorbidities (e.g., age, diabetes, malnutrition).
  • Dysphagia.

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1) initial consideration for the possibility of HAP

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When beginning to consider whether the patient might have HAP, roughly four pieces of information should be considered:

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(#1/4) evidence of inflammation

• Leukocytosis.
• Bandemia, left-shift, and neutrophil/lymphocyte ratio.
• Fever or hypothermia.
• Septic shock.

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(#2/4) evidence of pulmonary dysfunction

symptoms suggestive of pneumonia

• ? Cough.
• ? Production of purulent sputum.

general symptoms of respiratory failure

• Worsening oxygenation (requirement for increased FiO2).
• Tachypnea, respiratory distress.

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(#3/4) radiographic evidence

chest radiograph

• Chest radiography has poor performance in HAP.
• Sensitivity may be as low as 44%. (30028740) Imperfect sensitivity is due partially to portable films that often miss infiltrates hiding behind the heart or diaphragm. Among patients with pre-existing radiographic abnormalities, detecting a new infiltrate is even harder.
• Specificity is a major problem as well. For example, opacities may also represent atelectasis, aspiration pneumonitis, pulmonary infarction, chronic pulmonary fibrosis, or cardiogenic pulmonary edema.
• Repeat chest radiograph may sometimes help clarify the diagnosis. A true pneumonia will resolve very slowly, whereas atelectasis or aspiration can often resolve within 1-2 days.

lung ultrasonography

• Ultrasonography is less useful for HAP than for community-acquired pneumonia, because many patients in the ICU will have dependent consolidation and B-lines due to atelectasis.
• However, ultrasonography may remain useful (e.g., to distinguish pleural effusion vs. consolidation at the lung bases).

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(#4/4) alternative diagnostic considerations

• It's important to avoid falling into the trap of anchoring on a binary diagnostic approach (does the patient have HAP – yes or no?). A better approach is to consider all possibilities (e.g. what process does the patient have?). If an alternative diagnosis is established (e.g., empyema), this makes HAP unlikely.
• Some common alternative diagnoses to consider include the following:
  • Pulmonary embolism with infarction (which may produce infiltrates).
  • The combination of two processes:
    • #1 = Pulmonary process that doesn't cause inflammation: Atelectasis, asymmetric pulmonary edema, transudative pleural effusion.
    • #2 = Extrapulmonary inflammatory process: Infection elsewhere (e.g., line infection, Clostridioides difficile) or noninfectious fever (e.g., drug fever).
  • Aspiration pneumonitis.
  • Medication-induced pneumonitis.
  • Empyema.
• For a more detailed differential diagnosis, see the differential diagnosis of CAP (community-acquired pneumonia) here: 📖

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2) consider CT scan

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CT scan for HAP

• CT scan is the gold-standard imaging study for thoracic infection. Chest radiograph has been shown to have poor sensitivity and specificity as compared to CT scan. (30697596) The main drawback of CT scanning is the logistic challenge of transporting the patient to the CT scanner.
• CT scan may be extremely helpful when it reveals an alternative diagnosis, for example:
  • Aspiration pneumonitis.
  • Atelectasis.
  • Heart failure.
  • Pleural effusions.
  • Pulmonary embolism.
  • Large airway obstruction.
• Presence of pulmonary infiltrates doesn't prove the diagnosis of HAP. CT scan is exquisitely sensitive for mild infiltrates, so the presence of an infiltrate may be nonspecific. As with any radiologic study, be sure to review the images yourself and compare them to prior studies (radiologists may err on the side of safety by overcalling “possible pneumonia”).

how to protocol the CT scan

• CT angiography is preferred if pulmonary embolism is possible.
• If pulmonary embolism has been excluded, contrasted CT scan may still be helpful (for diagnosis of abscess, necrotizing pneumonia, atelectasis, and/or empyema).

argument for broader use of CT angiography in evaluation for possible HAP

• (1) Safety of CT scan:
  • New evidence shows that CT angiography doesn't cause kidney injury. 📖
  • Risk of secondary malignancy from radiation exposure is minimal, especially above ~30 years old (which describes most hospitalized patients).
• (2) Prompt diagnosis of HAP:
  • Hospital-associated pneumonia is associated with a mortality of ~30% or higher (far greater than, for example, STEMI).
  • HAP should be treated with respect, which includes securing a prompt and definitive diagnosis.
• (3) Characterization of HAP:
  • For patients who do have HAP, CT scan remains helpful in some cases:
  • (a) Cavitation, nodular lesions, lung abscess, or atypical radiographic patterns may help direct attention to specific pathogens.
  • (b) Early identification of parapneumonic effusions may facilitate appropriate monitoring and prompt intervention.
• (4) Antimicrobial stewardship:
  • Many cases of “possible HAP” are not in fact pneumonia. Misdiagnosis of HAP frequently leads to a week-long course of broad-spectrum antibiotics (while another cause of respiratory failure is being ignored).
  • CT scan may often immediately disprove a diagnosis of HAP, thereby avoiding unnecessary antimicrobial exposure (while shifting focus to the true etiology of respiratory failure – such as atelectasis).
• (5) Exclusion of PE (pulmonary embolism):
  • Among hospitalized patients with new-onset respiratory failure, the pre-test probability of pulmonary embolism will generally be >>2% (e.g., studies on critically ill patients commonly reveal a PE rate of ~15% among all patients!). (26283414) This risk is above the test threshold for pulmonary embolism, which makes further investigation for pulmonary embolism reasonable.
  • Although the diagnostic yield for pulmonary embolism for patients with suspected HAP will be low (perhaps in the 10% range), PE is a life-threatening diagnosis with important treatment implications.

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3) diagnosis & treatment for probable HAP

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additional diagnostic studies for a patient with probable HAP

• Blood cultures (two peripheral cultures, plus cultures of any central line in place >72 hours).
• Sputum for Gram stain & culture (If possible. Unfortunately, hospitalized patients are often incapable of expectorating sputum.)
• Nasal PCR for MRSA (repeat this if it wasn't recently performed).
• Nasal PCR for respiratory viruses
  • Unfortunately, respiratory viruses can be nosocomially acquired.
  • One study found that 24% of patients with HAP were positive for a respiratory virus. (30028739)
• Urine pneumococcal & Legionella antigens
  • Streptococcus pneumoniae is one of the most common pathogens among patients with HAP (which is unlike ventilator-associated pneumonia). (30028739)
  • Legionella is an uncommon HAP pathogen, but may occasionally contaminate hospital water supplies. Additionally, it's notable that patients with early-onset HAP (within <5 days of admission) may have various community-acquired atypical pathogens.
• Inflammatory markers:
  • Procalcitonin levels may be useful (in the absence of severe immune compromise).
  • C-reactive protein is an alternative (if procalcitonin is unavailable, or in severe renal failure).
• A repeat chest radiograph after 24-48 hours may be helpful:
  • If infiltrates rapidly disappear (within <24-48 hours), this suggests atelectasis or aspiration pneumonitis (rather than pneumonia). In true pneumonia, infiltrates take many days to weeks to resolve.
  • Stable or worsening infiltrates may support a pneumonia diagnosis.
  • Repeat chest radiograph is especially useful if a CT scan could not be obtained initially.

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empiric antibiotic therapy for HAP

If the patient is considered to have probable HAP, then initiation of antibiotics is appropriate. There are no precise criteria for exactly when to start antibiotics, so clinical judgement is required.

Pathogens involved in HAP are difficult to determine, as most patients are unable to provide high-quality sputum samples. The risk of drug-resistant organisms appears to lie in between the risk for CAP (lowest) and VAP (highest). Optimal antibiotic therapy is not well defined – and likely varies among different contexts, depending on local antibiograms.

occasionally, a treatment regimen for community-acquired pneumonia (CAP) is appropriate:

• CAP coverage is appropriate if all of the criteria listed below are met: (32157357)
  • (a) Patient admitted within <5 days (“early HAP”).
  • (b) Not recently admitted to the hospital or treated with IV antibiotics (within 90 days).
  • (c) Not immunosuppressed.
  • (d) Structurally normal lungs (e.g., no bronchiectasis or severe COPD).
  • (e) Not in septic shock.
  • (f) No ARDS or acute dialysis prior to HAP onset.
  • (g) No prior colonization with multidrug-resistant bacteria.
• For more on appropriate antibiotics for community-acquired pneumonia, look here.

Most patients will require an antibiotic regimen for HAP, which will involve: 

backbone agent: Antipseudomonal beta-lactam

• A broad-spectrum antipseudomonal agent is the backbone of therapy.
• This is generally cefepime or piperacillin/tazobactam (more on comparison of these antibiotics here: 📖). Meropenem may occasionally be considered, if there is concern for an extended-spectrum beta-lactamase resistance organism (ESBLs).
• Factors to consider:
  • Recent antibiotic exposure (an agent which they weren't exposed to might be preferable).
  • Prior infection or colonization with drug-resistant organisms.
• Double coverage of pseudomonas generally isn't evidence based and may increase toxicity. 🌊 However, double coverage of gram-negative pathogens could be considered if multiple agents are required to cover >90% of gram-negative organisms (based on local antibiograms and consultative practices). (30028739)

MRSA coverage?

• Not all patients with HAP require MRSA coverage:
  • Roughly half of patients with probable HAP won't be found to have an actual pneumonia. The overall risk of MRSA pneumonia will depend on MRSA prevalence within any individual hospital unit, but it's often quite low.
  • Patients with a recent nares PCR that was negative for MRSA don't require MRSA coverage. (Murray 2022; 29340593)
• Some risk factors for MRSA that require consideration include: (27418577)
  • Receipt of intravenous antibiotics within the last 90 days.
  • Hospitalization in a unit where MRSA is common (e.g., >20% of Staph. aureus isolates are MRSA).
  • Patients at high risk of mortality (e.g., septic shock, more severe pneumonia).
  • Known colonization with MRSA.
• If MRSA coverage is indicated, this is generally achieved with linezolid or vancomycin. More on vancomycin versus linezolid here: 📖

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4) review data & course over 24-72 hours

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Many patients who are started on empiric antibiotics won't ultimately be diagnosed with pneumonia. Therefore, it's essential to reconsider the diagnosis as additional information becomes available. If emerging evidence is inconsistent with a diagnosis of pneumonia, antibiotics should be discontinued and the diagnosis should be discarded.

(1) Consider data that may question the diagnosis of HAP, for example:

• Procalcitonin:
  • Procalcitonin may be helpful among patients who are not immunosuppressed.
  • A procalcitonin value of <0.25 argues against HAP. This should prompt consideration of discontinuing antibiotics.
• Repeat chest radiograph shows rapid clearance, inconsistent with bacterial pneumonia (discussed above).
• Blood cultures:
  • Blood cultures are only occasionally positive in HAP (perhaps roughly 10% of the time).
  • If blood cultures are positive, be thoughtful about looking for a nonpulmonary focus of infection – especially if blood cultures reveal an organism which doesn't usually cause pneumonia (e.g., Candida, Enterococcus). (33004324)

(2) Discontinue MRSA coverage within 48 hours unless there is objective data of MRSA

• MRSA coverage should be discontinued within <48 hours in the absence of any evidence that the patient has MRSA (e.g., a positive MRSA PCR or blood culture).
• If a recent MRSA nares PCR is negative, this is generally sufficient evidence to discontinue anti-MRSA therapy. (Murray 2022; 29340593)

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5) ongoing management of HAP

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If HAP remains the leading diagnosis, then antibiotics should be continued to complete a course.

duration of antibiotic therapy

• The IDSA/ATS guidelines generally recommend a seven-day course of antibiotics (even for Pseudomonas). (27418577)
• Potential indications for prolonged therapy: (32157357, 30601179)
  • Empyema.
  • Lung abscess or necrotizing pneumonia.
  • Bacteremia with certain gram-positive organisms (e.g., Staph. aureus).
  • Severe immunodeficiency.
  • Cystic fibrosis.
• Procalcitonin may occasionally be useful to shorten the duration of therapy:
  • Procalcitonin levels falling below 20% of the initial value or <0.25 ng/ml suggests that it is safe to discontinue antibiotics.
  • Procalcitonin should be used only as an antibiotic-stopping tool. Therefore, a low procalcitonin may support discontinuation of antibiotics before seven days. Antibiotics should generally be discontinued after a seven-day course, regardless of the procalcitonin level.

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approach to treatment failure

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• The diagnosis of HAP is rarely entirely secure (due to difficulty in obtaining high-quality sputum for analysis).
• If patients aren't responding to therapy, it's important to reconsider the diagnosis. Unfortunately, it may also be possible that the patient is infected with a drug-resistant organism which is not being covered by current antibiotics.
• The approach to treatment failure is similar to that for community-acquired pneumonia, discussed here: 📖

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bronchoscopy in HAP

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bronchoscopy is generally not utilized in HAP

• Among patients who aren't intubated, the risk of sedation and bronchoscopy is increased.
• Available evidence hasn't found an improvement in patient outcomes following bronchoscopy (as compared to empiric antibiotic therapy). (19154492, 30028739)

potential indications for bronchoscopy

• Severe immunosuppression creates a very broad differential diagnosis for the potential infection (e.g., organ transplantation patients).
• CT scan reveals nodular or cavitary lesions which increase the likelihood of unusual pathogens (such as fungi).
• Failure to respond to empiric antimicrobial therapy.
• Suspected alternative diagnosis that requires bronchoscopy for diagnosis (e.g., possible eosinophilic pneumonia, or possible diffuse alveolar hemorrhage).

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questions & discussion

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To keep this page small and fast, questions & discussion about this post can be found on another page here.

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