AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Background

An understanding of the following terminology used to describe nosocomial pneumonias is important.

• Hospital-acquired pneumonia (HAP) is pneumonia that develops 48 hours or longer after admission to a hospital.
• Ventilator-associated pneumonia (VAP) is pneumonia that develops 48 hours or longer after mechanical ventilation is given by means of an endotracheal tube or tracheostomy.
• Health care–associated pneumonia is pneumonia that occurs in persons in one of the following groups:
• • Patients who have been hospitalized in an acute care facility for 2 or more days within 90 days of the infection
  • Residents of a nursing home or long-term care facility
  • Patients who received intravenous antibiotic therapy, chemotherapy, or wound care within the last 30 days of the current infection
  • Patients who receive hemodialysis in any setting

HAP is the second most common nosocomial infection (see Nosocomial Pneumonia). HAP increases a patient's hospital stay by approximately 7-9 days and can increase hospital costs by an average of $40,000 per patient.^{1, 2, 3}

The Medscape CME courses What's New in Ventilator-Associated Pneumonia and Critical Decisions for the Treatment of Health-care-Associated Pneumonia in the ICU may be of interest, as may the eMedicine article Pneumonia, Community-Acquired.

Pathophysiology

VAP results from the invasion of the lower respiratory tract and lung parenchyma by microorganisms. Intubation compromises the integrity of the oropharynx and trachea and allows oral and gastric secretions to enter the lower airways.

Frequency

International

VAP is a complication in as many as 28% of patients who receive mechanical ventilation. The incidence of VAP increases with the duration of mechanical ventilation. Estimated rates are 3% per day for the first 5 days, 2% per day for days 6-10, and 1% per day after day 10.⁴

Mortality/Morbidity

The crude mortality rate for VAP is 27-76%. Pseudomonas or Acinetobacter pneumonia is associated with increased mortality rates compared with other organisms. Studies have consistently shown that a delay in starting appropriate and adequately dosed antibiotic therapy increases the mortality risk.

Outcomes are also related to the timing of the onset of VAP. Early-onset pneumonia occurs within the first 4 days of hospitalization, whereas late-onset VAP develops 5 or more days after admission. Late-onset pneumonias are usually associated with multidrug-resistant (MDR) organisms.

Race

No specific data are available.

Sex

No specific data are available.

Age

No specific data are available.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

History

Risk factors for MDR pathogens

The patient's medical history should include an assessment for risk factors related to MDR pathogens. Such risk factors include the following:

• Current hospitalization admission of greater than 5 days
• Hospital admission more than 2 days in the preceding 90 days
• Antibiotic use in the previous 90 days
• Residence in a nursing home or extended-care facility
• Home infusion therapy and wound care
• Long-term dialysis within 30 days
• Immunocompromise

This assessment is important so that appropriate empiric antibiotics can be initiated before bacterial culture results return. If appropriate empiric antibiotics are selected, the subsequent adjustment of antibiotics does not improve the patient's mortality risk.

Diagnostic triad for VAP

The diagnostic triad for VAP consists of the following clinical criteria:

• Pulmonary infection: Signs include fever, purulent secretions, and leucocytosis.
• Bacteriologic evidence of pulmonary infection: See Other Tests.
• Radiologic suggestion of pulmonary infection: See Imaging Studies.

Causes

Multiple factors should be considered when addressing the issues of HAP and VAP. These factors include the following (also see History):

• Whether or not to intubate the patient
• The roue of intubation or placement of tubes
• Feeding the patient
• Body positioning
• Prevention of stress-related bleeding
• Prevention of deep venous thrombosis
• Use of antibiotics and control of colonization

Mechanical ventilation

Intubation with mechanical ventilation increases the risk of HAP 3- to 21-fold^{6, 7, 8, 5} and should be avoided if possible. Noninvasive positive-pressure ventilation is an option to consider, especially in the following groups:

• Patients with exacerbations of chronic obstructive pulmonary disease
• Patients with acute hypoxic respiratory failure
• Patients with immunosuppression and respiratory failure

Orotracheal and orogastric tubes are preferred over nasal devices to reduce the risk of VAP, although direct causality has not been proven.

Continuous aspiration of subglottic secretions reduces the risk of early-onset VAP. Cuff pressures should be maintained at greater than 20 cm of water to prevent aspiration around the endotracheal tube.

Passive humidifiers or heat moisture exchangers are preferred to reduce colonization of the ventilator circuit. Ventilatory-circuit condensation should be prevented from entering the endotracheal tubes and any inline nebulizer. Frequent changes of the ventilator circuit, however, have not been shown to reduce the risk of VAP and are currently not recommended.

Protocols for sedation and weaning should be applied in the ICU to reduce the duration of mechanical ventilation.

Feeding, aspiration, and body positioning

Placing patients in a semirecumbent position is associated with approximately a 3-fold reduction in the risk of HAP,⁹ especially during enteral feeding.

Early enteral feeding is currently recommended. Although this route of feeding is associated with an increased incidence of HAP, it offers a number of advantages in delivering nutrition. Investigators have compared the risks of ICU-acquired HAP between gastric and postpyloric feeding. Individual studies have shown no significant differences. A meta-analysis of these studies has suggested a significant reduction in ICU-acquired HAP.¹⁰

Prevention of stress-related bleeding

Studies comparing H2 receptor blockers with sucralfate have shown conflicting results, with a trend toward a reduction of VAP with the use of sucralfate.^{11, 12, 13} These benefits were most notable with late-onset VAP. Use of sucralfate is associated with a 4% increase in clinically significant bleeding. Proton pump inhibitors also may be used to prevent stress-related gastrointestinal bleeding.

Prevention of deep venous thrombosis

Measures should be taken to prevent deep venous thrombosis. The selection for the method of deep venous thrombosis prevention should be based on individual patient characteristics and comorbid illnesses. Heparin, low molecular weight heparin, and compression stockings are means to help prevent deep venous thrombosis.

Use of antibiotics and control of colonization

Rinses with oral chlorhexidine help prevent ICU-acquired HAP in patients undergoing coronory artery bypass procedures.¹⁴

A history of antibiotic use prior to the onset of VAP increases the probability of infection with MDR pathogens.

Alteration of the florae in the digestive tract due to oral or systemic antibiotics (ie, selective decontamination of the digestive tract) effectively reduces the incidence of ICU-acquired HAP in ICUs where the levels of antibiotic resistance are low. However, routine use of this approach is not recommended.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Lab Studies

Routine blood tests should be obtained to evaluate the patient for infection (white blood cell count) and to assess the patient's baseline renal and hepatic function for dosing of antibiotics. Blood cultures should also be obtained.

Samples of respiratory secretions from the distal respiratory tract with either bronchoscopic or nonbronchoscopic tests should be considered. Examples of these tests are blind bronchoalveolar lavage (BAL), bronchoscopic BAL, bronchoscopy-guided protected-specimen brush (PSB) sampling, and blind PSB sampling. Quantitative bacterial cultures are generally recommended to increase the reliability of these respiratory sampling techniques. The authors of this article prefer to use the bronchoscopy-guided techniques.

New markers, such as procalcitonin and triggering receptors expressed on myeloid cells (TREM-1) are being evaluated, but large clinical trials are not yet completed.

Imaging Studies

In the ICU, portable chest radiography is commonly used in the diagnosis  of VAP. No single radiographic sign has diagnostic accuracy better than 68%. Air bronchograms are probably the best predictor for a VAP. Among patients in the ICU, many infectious and noninfectious processes may cause the radiologic appearance of infiltrates. The absence of a radiologic infiltrate is helpful in excluding the diagnosis of VAP.

Chest CT scanning can be performed to evaluate the patient for underlying lung parenchyma disease, pleural effusions, and attenuation of consolidations.

Ultrasonography of the chest may be obtained to aid in the evaluation for pleural effusions and to guide sampling or drainage of the pleural fluid.

Other Tests

To evaluate bacteriologic evidence of pulmonary infection, samples of respiratory secretions may be obtained from the proximal and/or distal airways by using bronchoscopic or nonbronchoscopic techniques.

Some authorities suggest that bacteremia and/or positive cultures of pleural fluid help in identifying etiologic pathogens. For this reason, 2 sets of blood cultures are recommended. If a sufficient amount of pleural fluid is present to allow the effusion to be safely obtained for diagnostic tests, the pleural effusion should be sampled. The general recommendation is to perform a diagnostic thoracentesis under ultrasound guidance for mechanically ventilated patients. 

Sampling of secretions in the proximal airway

Qualitative endotracheal aspirates are easy to obtain but have a high false-positive rate in ICU patients because of airway colonization. When quantitative endotracheal-aspirate cultures are used, a cutoff value of 10⁶ is the most accurate, with a sensitivity of 38-82% and a specificity of 72-85%. However, when this cutoff is used, approximately 33% of patients with VAP may be missed. Only 40% of endotracheal-aspirate cultures coincide with results of protected brush sampling. Therefore, adjusting antibiotics on the basis of findings from endotracheal aspirates may lead to inadequate coverage of the causative pathogens.

Sampling of secretions in the distal airway

Distal airway samples may be obtained by using bronchoscopic or nonbronchoscopic techniques. With nonbronchoscopic techniques, a catheter is blindly advanced through the endotracheal tube or tracheostomy and wedged in the distal airway. Various sampling methods include blind bronchial suction (BBS), blind BAL, and blind PSB sampling. Their sensitivities and specificities, respectively, are as follows¹⁵:

• BBS - 74-97% and 74-100%
• Blind BAL - 63-100% and 66-96%
• Blind PSB sampling - 58-96% and 71-100%

When nonbronchoscopic techniques are used, the diagnostic threshold may vary according to the method used. Cultures tend to be above the diagnostic threshold with bronchoscopic procedures more often than they are with nonbronchoscopic procedures.

Bronchoscopic sampling

For bronchoscopic sampling of the distal airway, a bronchoscopist must be available. Bronchoscopy is performed and specimens are retrieved from specific areas of the bronchial tree. Regions to be sampled are determined from imaging studies, areas of maximal bronchial abnormality, or dependent airway segments.

The techniques are usually BAL and PSB sampling. With BAL, an aliquot of at least 120-250 mL of nonbacteriostatic sodium chloride solution is introduced through the wedged bronchoscope. When BAL is adequately performed, approximately 1 million alveoli are sampled.

As with any sampling procedure, proper technique is imperative to obtain reliable results. Because contamination from the oropharynx inevitably occurs during BAL, quantitative thresholds of less than 10⁴ colony-forming units (cfu)/mL are generally considered contaminants, whereas those in the range of 10⁵-10⁶ cfu are considered true pathogens.

With the bronchoscopic PSB method, the distal airway is sampled by telescoping the brush out of a sheath with a protective cap. When adequately performed, the sensitivity and specificity of bronchoscopic PSB sampling are approximately 89% and 94%, respectively. Because the clinician can retrieve 0.001- to 0.01-mL secretions (diluted in 1 mL of sodium chloride solution), a threshold of 10³ represents a sample of 10⁵-10⁶ cfu/mL.

Sensitivities and specificities of bronchoscopic BAL and PSB sampling, respectively, are as follows¹⁶:

• BAL - 42-93% and 45-100%
• PSB sampling - 33-100% and 50-100%

Procedures

Thoracentesis may be indicated to determine whether or not the pleural space is infected. Additionally, when the etiology of the pulmonary infiltrates remains unclear, procedures such as video-assisted thoracotomy or an open lung biopsy may be required to establish a diagnosis. Lung biopsy has been tolerated well, even in patients with adult respiratory distress syndrome. The authors' bias is to achieve early diagnosis before further clinical deterioration occurs.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Medical Care

Patients with severe HAP or health care–acquired pneumonia who require mechanical ventilatory support should be treated similarly to patients with VAP.

Selection of antibiotics

Outcomes after VAP improve with the early administration of appropriate antibiotic regimens and with adequate dosing of antibiotics.

Antibiotics should be further adjusted on the basis of culture results. The first antibiotic regimen should be optimized because inappropriate initial therapy is associated with worsened outcomes, even if the regimen is subsequently changed on the basis of the microbiologic results.

The 10 clinical caveats in selecting an empiric antibiotic regimen are as follows:

• The administration of antibiotics should not be delayed for the sole purpose of performing diagnostic tests.
• The empiric choice of antibiotic should be based on the patient's risk for having MDR pathogens.
• Combination therapies are preferred as the initial regimens in patients at risk for infection with MDR pathogens to avoid inappropriate antibiotics.
• Local antibiograms should be reviewed when empiric therapy is being selected.
• If the patient received antibiotics in the recent past, the new antibiotic should be chosen from a class different from the previous ones to avoid selecting antibiotics to which the bacterial pathogen has become resistant.
• When an appropriate and adequate initial antibiotic regimen is started, every effort should be made to shorten the duration of antibiotic therapy. If a patient receives appropriate and adequate empiric antibiotic therapy, the duration of antibiotic treatment may be shortened from the traditional 14-21 days to 7 days if the etiologic organism is not Pseudomonas aeruginosa.
• False-negative culture results occur in patients who have been taking antibiotics for 24-72 hours before the collection of respiratory specimens. In these patients, using a BAL threshold 10-fold lower than usual may be helpful for avoiding false-negative results.
• If the clinical pretest probability for VAP is high, antibiotics should be started promptly regardless of whether the culture results are positive.
• Aerosolized antibiotics may be used as an adjunct to systemic antibiotics, although they have not been shown to be effective as sole therapy for VAP.
• Certain organisms, such as Escherichia coli, Klebsiella species, and Enterobacter species produce extended-spectrum beta-lactamase (ESBL), and screening tests for the production of ESBL should be performed. Carbapenems are generally effective against these ESBL-producing organisms.

Patterns of antibiotic resistance

Clinicians should be aware of the local antibiotic resistance pattern in order to adequately begin an empiric antibiotic regimen. Other important factors are an adequate dose, the route of administration, and an understanding of the pharmacodynamic properties of particular antibiotics.

Beta-lactam antibiotics achieve less than 50% of the serum concentration in the lung, whereas fluoroquinolones and linezolid are found in comparable concentrations in bronchial secretions.

Aminoglycosides and quinolones are bactericidal in a concentration-dependent manner. In comparison, agents such as vancomycin and beta-lactams are bactericidal in a time-dependent fashion; that is, their bactercidal activity depends on the time the serum concentration is above the minimal inhibitory concentration for the target organism.

Postantibiotic effects

A postantibiotic effect is the ability of an antibiotic agent to suppress bacterial growth even after its levels decrease below the minimal inhibitory concentration for the organism.

When used to treat gram-negative bacilli, aminoglycosides and fluoroquinolones have a prolonged postantibiotic effect. On the contrary, beta-lactam antibiotics have a short postantibiotic effect against these organisms.

An understanding of the principles described above helps in adjusting intervals and doses of antibiotics. For example, aminoglycosides and quinolones are administered less often than other drugs and with doses that maximize initial serum concentrations. Aminoglycosides have been dosed by combining an entire day's therapy into a single dose. This type of dosing regimen takes advantage of the postantibiotic effect of the agent and its concentration-dependent killing ability.

MEDICATION

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

For patients with early-onset VAP and no risk factors for MDR pathogens, currently recommended initial empiric antibiotics are 1 of the following options:

• Ceftriaxone
• Fluoroquinolones
• Ampicillin-sulbactam
• Ertapenem

For patients with VAP and risk factors for MDR pathogens or for patients with late-onset VAP, initial antibiotic therapy may involve 1 of the following options:

• Antipseudomonal cephalosporins (eg, cefepime, ceftazidime)
• Antipseudomonal carbapenems (imipenem or meropenem)
• Beta-lactam/beta-lactamase inhibitors (piperacillin-tazobactam) with an antipseudomonal fluoroquinolone (ciprofloxacin) or aminoglycoside plus linezolid or vancomycin (if risk factors for methicillin-resistant Staphylococcus aureus are present)

If infection with Legionella pneumophila is suspected, the regimen should include a macrolide or fluoroquinolone rather than an aminoglycoside.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

FOLLOW-UP

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

Further Inpatient Care

Treatment failure may occur in 30% of patients who develop VAP, resulting in adverse outcomes. Therefore, patients should be closely monitored for therapy failure. Causes of treatment failure include the following:

• Inadequate treatment in terms of the choice and dosage of antibiotics
• Wrong diagnosis
• Development of resistance with Pseudomonas, Enterobacter, or other species during treatment
• Superinfection
• Development of concomitant infection
• Complications of VAP (eg, abscess, empyema)

Deterrence/Prevention

See Causes.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• References

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Article Last Updated: Sep 4, 2008