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Hospital-Acquired Pneumonia

By Sanjay Sethi, MD, Professor and Chief, Pulmonary, Critical Care and Sleep Medicine and Vice Chair for Research, School of Medicine and Biomedical Sciences, University at Buffalo SUNY

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Hospital-acquired pneumonia (HAP) develops at least 48 h after hospital admission. The most common pathogens are gram-negative bacilli and Staphylococcus aureus; antibiotic-resistant organisms are an important concern. Symptoms and signs include malaise, fever, chills, rigor, cough, dyspnea, and chest pain, but in ventilated patients, pneumonia usually manifests as worsening oxygenation and increased tracheal secretions. Diagnosis is suspected on the basis of clinical presentation and chest x-ray and is confirmed by blood culture or bronchoscopic sampling of the lower respiratory tract. Treatment is with antibiotics. Overall prognosis is poor, due in part to comorbidities.

(See also Overview of Pneumonia.)

Hospital-acquired pneumonia includes ventilator-associated pneumonia (VAP), postoperative pneumonia, and pneumonia that develops in unventilated hospitalized inpatients.

Etiology

The most common cause of hospital-acquired pneumonia is microaspiration of bacteria that colonize the oropharynx and upper airways in seriously ill patients. Seeding of the lung due to bacteremia or inhalation of contaminated aerosols (ie, airborne particles containing Legionella sp, Aspergillus sp, or influenza virus) are less common causes (see Overview of Pneumonia).

Risk factors

Endotracheal  intubation with mechanical ventilation poses the greatest overall risk of hospital-acquired pneumonia; ventilator-associated pneumonia constitutes > 85% of all cases, with pneumonia occurring in 9 to 27% of mechanically ventilated patients. The highest risk of VAP occurs during the first 10 days after intubation. 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.

In nonintubated patients, risk factors include previous antibiotic treatment, high gastric pH (due to stress ulcer prophylaxis or therapy with H2 blockers or proton pump inhibitors), and coexisting cardiac, pulmonary, hepatic, or renal insufficiency.

Major risk factors for postoperative pneumonia are age > 70, abdominal or thoracic surgery, and functional debilitation.

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 determination of appropriate empiric antibiotic therapy. In general, the most important pathogens are Pseudomonas aeruginosa, methicillin-sensitive Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA).

Other important pathogens include enteric gram-negative bacteria (mainly Enterobactersp, Klebsiella pneumoniae, Escherichia coli, Serratia marcescens, Proteus sp, and Acinetobacter sp).

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 intravenous antibiotic treatment (within the previous 90 days) greatly increases the likelihood of antibiotic-resistant organisms, particularly MRSA and Pseudomonas infection in VAP and HAP (1). Infection with a resistant organism markedly worsens mortality and morbidity. Other risk factors for antibiotic-resistant organisms specific to VAP include

  • Septic shock at time of VAP

  • ARDS preceding VAP

  • Five or more days of hospitalization prior to the occurrence of VAP

  • Acute renal replacement therapy prior to VAP onset

High-dose corticosteroids increase the risk of Legionellaand Pseudomonas infections. Chronic suppurative lung diseases such as cystic fibrosis and bronchiectasis increase the risk of Gram-negative pathogens, including antibiotic-resistant strains.

Etiology 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. Clinical Infectious Diseases 63(5):e61–111, 2016.

Symptoms and Signs

Symptoms and signs of hospital-acquired pneumonia in nonintubated patients are generally the same as those for community-acquired pneumonia and include malaise, fever, chills, rigor, cough, dyspnea, and chest pain. Pneumonia in critically ill, mechanically ventilated patients more 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

  • Chest x-ray and clinical criteria (limited accuracy)

  • Sometimes bronchoscopy or blood cultures

Diagnosis is imperfect. In practice, hospital-acquired 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, pulmonary embolism, or pulmonary edema and may be part of the clinical findings in acute respiratory distress syndrome.

Gram stain and semiquantitive cultures of endotracheal aspirates, though not definitive for identifying infection, are recommended for guiding treatment in VAP. 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 relatively specific if a respiratory pathogen is identified but are insensitive.

Prognosis

The mortality associated with hospital-acquired pneumonia ranges from 25 to 50% 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 other underlying illness. Adequacy of initial antimicrobial therapy clearly improves prognosis. Infection with antibiotic-resistant gram-negative or gram-positive bacteria worsens prognosis.

Treatment

  • Empirically chosen antibiotics active against resistant organisms

If hospital-associated pneumonia is suspected, treatment is with antibiotics that are chosen empirically based on

  • Local sensitivity patterns

  • Patient risk factors for 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 HAP/VAP requiring broad-spectrum antibiotic therapy for MRSA and resistant Pseudomonas. New recommendations in 2016 (1) emphasize use of a narrower spectrum of empiric antibiotics when possible. Empiric therapy for HAP/VAP without risk factors for antibiotic-resistant organisms and high mortality (mechanical ventilation for pneumonia or septic shock), in an institution where MRSA incidence is < 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

Doses depend on renal function (see Table: Usual Doses of Commonly Prescribed Antibiotics).

In treatment settings where MRSA rates are > 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, which 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. Clinical Infectious Diseases 63(5):e61–111, 2016.

Prevention

Among cases of hospital-acquired infection, the most effective preventative measures are those that focus on 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 (BiPAP) prevents the breach in airway defense that occurs with endotracheal intubation and eliminates the need for intubation in some patients.

Continuous aspiration of subglottic secretions using a specially designed endotracheal tube attached to a suction device seems to reduce the risk of aspiration.

Selective decontamination of the oropharynx (using topical gentamicin, colistin, chlorhexidine, vancomycin cream, or a combination) or of the entire GI tract (using polymyxin, 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 VAP, has not been shown to decrease mortality.

Surveillance cultures and routinely changing ventilator circuits or endotracheal tubes have not been shown to decrease VAP.

Incentive spirometry is recommended to help prevent postoperative pneumonia.

Key Points

  • Hospital-acquired pneumonia (HAP) includes ventilator-associated pneumonia, postoperative pneumonia, and pneumonia that develops in unventilated patients who have been hospitalized for at least 48 h.

  • Mechanical ventilation is the most important risk factor for HAP.

  • Likely pathogens differ from those causing community-acquired pneumonia and 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.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • NYSTOP
  • IQUIX, LEVAQUIN, QUIXIN
  • CILOXAN, CIPRO
  • MERREM
  • TOBI, TOBREX
  • VANCOCIN
  • ZYVOX
  • FORTAZ, TAZICEF
  • MAXIPIME
  • GENOPTIC
  • No US brand name

* This is the Professional Version. *