eMedicine - Nosocomial Pneumonia : Article by Burke A Cunha, MD, MACP

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Nosocomial Pneumonia

Last Updated: May 2, 2006

Synonyms and related keywords: NP, hospital-acquired pneumonia, HAP, community-acquired pneumonia, CAP, ventilator-associated pneumonia, VAP

AUTHOR INFORMATION Section 1 of 11

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Author: Burke A Cunha, MD, MACP, Professor of Medicine, State University of New York at Stony Brook School of Medicine; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD, MACP, is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Editor(s): Wesley W Emmons, MD, FACP, Assistant Professor, Department of Medicine, Thomas Jefferson University; Consulting Staff, Infectious Diseases Section, Department of Internal Medicine, Christiana Care, Newark, DE; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Ronald A Greenfield, MD, Chief, Professor, Department of Internal Medicine, Section of Infectious Disease, University of Oklahoma College of Medicine; Eleftherios Mylonakis, MD, PhD, Assistant Professor of Medicine, Harvard Medical School, Clinical Assistant in Medicine, Division of Infectious Disease, Massachusetts General Hospital; and Michael E Zevitz, MD, Assistant Professor of Medicine, Finch University of the Health Sciences, The Chicago Medical School; Consulting Staff, Private Practice

Disclosure

INTRODUCTION

Section 2 of 11

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Background: A working definition of nosocomial pneumonia (NP) is that of a new pulmonary infiltrate that occurs after one week of hospitalization and that resembles a bacterial pneumonia on the chest radiograph. Although most patients have fever and leukocytosis, these findings are not uniformly present nor are they a requisite for the presumptive diagnosis of NP.

Some hospitalized patients develop pneumonia in less than 5 days, a condition called early hospital-acquired pneumonia (HAP), which is better known as incubating community-acquired pneumonia (CAP). Since NP is defined as occurring a week or more after hospitalization, the early cases should not be regarded as NP but as CAP. Both early HAP and CAP have the same etiology in that the main pathogens are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, although atypical pathogens also may cause the conditions.

NP is caused by different pathogens, the aerobic gram-negative bacilli (ie, excluding H influenzae). Pseudomonas aeruginosa is not the most common cause of NP but is the most important organism in terms of mortality and morbidity. Staphylococcus aureus (ie, methicillin-susceptible S aureus [MSSA], methicillin-resistant S aureus [MRSA]) and anaerobic organisms are not significant contributors to NP.

Pathophysiology: Since aerobic gram-negative bacilli cause all cases of NP, the pathophysiology relates to the destructive effect of these organisms on invaded lung tissue. Aerobic gram-negative pathogens may be divided into 2 categories. The first category includes those organisms causing necrotizing pneumonia with rapid cavitation, microabscess formation, blood vessel invasion, and hemorrhage; typically, this is characteristic of P aeruginosa. The second category consists of all other nonnecrotizing gram-negative organisms responsible for NP that cause histologically indistinguishable nonnecrotizing pneumonia.

National Nosocomial Infection Surveillance (NNIS) surveys indicate that S aureus causes approximately 20% of the infections. See the Centers for Disease Control and Prevention web site for more information. These surveys are based on endotracheal aspirate cultures. They reflect staphylococcal colonization of the hospitalized patient and do not reflect the etiology of NP. In a patient with CAP, S aureus is a postviral influenza that produces a pneumonia similar to that produced by the Pseudomonas species (ie, it causes necrotizing pneumonia, with rapid cavitation in 72 hours or less, which is characterized histologically by blood vessel invasion, microabscesses, and hemorrhage). If S aureus caused by MRSA or MSSA indeed were responsible for 20% of the patients diagnosed with NP, then this characteristic picture would occur in 1 of 5 patients, which is not the case. In fact, S aureus NP is so rare that it is listed as a reportabledisease. Most patients with S aureus pneumonia show symptoms of fever, pulmonary infiltrates, and leukocytosis, with S aureus cultured from the airways and peripheral blood cultures. Patients with S aureus NP do not meet the histologic or radiologic criteria for S aureus pneumonia. A blood culture that is positive usually is caused by contamination during the blood culture collecting process, eg, by S aureus on the skin or from an IV line infection unrelated to the pulmonary process.

Frequency:

In the US: NP is one of the most common diagnoses occurring in medical and surgical intensive care units (ICUs) and is frequent in patients receiving mechanical ventilation. NP also occurs in patients on the general hospital wards who are not being ventilated.

Internationally: The microorganism incidence and frequency are the same as that of the United States.

Mortality/Morbidity:

As patients in ICUs are critically ill, mortality and morbidity are high. Intubation and ventilatory support bypass the normal host defense mechanisms, add to mortality and morbidity.

Race: No racial differences exist.

Sex: No sexual predilection exists.

Age: NP is most common in elderly patients; however, patients of any age may be affected.

CLINICAL

Section 3 of 11

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History:

Respiratory tract symptoms, which may include an increase in respiratory rate, shortness of breath, and a productive cough are present.

Fever usually, but not always, is present.

Definitive diagnosis

The definitive diagnosis of NP rests on tissue biopsy; therefore, the clinician is forced to grapple with a variety of nonspecific findings that can mimic NP. This situation particularly is true of pulmonary infiltrates on the chest x-ray, which may be caused by a number of conditions common in the critical care setting.

The most common causes of infiltrates in the ventilated patient with fever and/or leukocytosis include the following:
Congestive heart failure
Pulmonary embolus or infarction
Acute respiratory distress syndrome (ARDS)
Pulmonary drug reactions
Collagen vascular diseases (eg, systemic lupus erythematosus (SLE), bronchiolitis obliterans-organizing pneumonia (BOOP), interstitial lung disease, bronchogenic carcinomas, metastatic carcinomas, radiographic artifacts (see Picture 1)

Physical:

Findings in NP relate to the pneumonia distribution in the chest. Lobar lesions are the same physically as for any other pneumonia (eg, rales in the location of the pneumonic process).

Consolidation usually is not a feature of NP nor are pleural effusions; therefore, consider an alternative diagnosis if either of these features is present.

The presumptive diagnosis of NP is clinical and based on nonspecific findings; therefore, it is not necessarily precise. Most patients in the ICU who have fever and pulmonary infiltrates probably do not have NP; nonetheless, therapy should be based on a clinical diagnosis since tissue-based biopsy methods are not employed in the majority of patients.

Several conditions mimic the diagnosis of NP; therefore, incorporate the exclusion of these conditions as part of the clinical diagnosis.

Causes: Inhalation, aspiration, and hematogenous spread are the 3 main mechanisms by which bacteria reaches the lungs.

Factors that predispose to infection

Primary inhalation pneumonia develops when these organisms bypass normal respiratory defense mechanisms or when the patient inhales aerobic gram-negative organisms that colonize the upper respiratory tract or respiratory support equipment.

Aspiration pneumonia occurs when the patient aspirates colonized upper respiratory tract secretions.

The stomach appears to be an important reservoir of gram-negative bacilli that can ascend, colonizing the respiratory tract.

Hematogenously acquired infections originate from a distant source and reach the lungs via the blood stream. In bacteremic NP, blood cultures frequently are positive if obtained early in the disease process and if the patient is not already receiving antimicrobial therapy.

Table 1. Microbiology of Nosocomial Pneumonia

Pathogens Comments
Common causes of NP
P aeruginosa
Klebsiella
E coli
S pneumoniae
H influenzae
Many cases diagnosed as nosocomial pneumonia probably are not pneumonias.
Uncommon pathogens
Serratia
Acinetobacter
Legionella Acinetobacter is a common colonizer of respiratory tract secretions in the ICU.
Acinetobacter and Legionella NP occur only in outbreaks or clusters.

Nonpathogens of NP
Enterobacter
Stenotrophomonas (formerly Pseudomonas) maltophilia
Burkholderia (formerly Pseudomonas) cepacia
S aureus (MSSA, MRSA)
Oropharyngeal anaerobes (non-B fragilis) These rarely, if ever, are proven as causes of documented NP.
The recovery of an organism that is a pathogen from respiratory secretions does not prove that it is pathogenic and the cause of NP.
Early pathogen group
(�5 d after admission)
S pneumoniae
H influenzae
M catarrhalis

The so-called early group of nosocomial pathogens usually represents an incubating CAP that manifests early after hospital admission. For this reason, early pathogens are the same as CAP pathogens.
Late pathogen group
(�5 d after admission)
Aerobic gram-negative bacilli Early versus late classification schemes have no clinical relevance except to alert clinicians to the fact that the early group has the same pathogens and prognosis as CAP. The late group has the same pathogens and prognosis as traditional NPs.
Multiple organisms as a cause of NP Multiple pathogens are proof of lower airway colonization obtained by nontissue biopsy culture methods.

DIFFERENTIALS

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Acute Respiratory Distress Syndrome
Pulmonary Edema, Cardiogenic
Pulmonary Embolism

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WORKUP

Section 5 of 11

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Lab Studies:

Perform tests on all patients with presumed NP to rule out conditions that mimic NP. The presumptive diagnosis of NP is difficult because the diagnosis does not depend on the presence of fever and leukocytosis is unhelpful.

Lung tissue

Obtain lung tissue to demonstrate the organism invading the lung parenchyma, which definitely identifies NP.

Obtain this tissue using percutaneous fine-needle aspiration, transbronchial biopsy, or open lung biopsy.

In a critical care setting, these modalities are underutilized and various bronchoscopic techniques approximate definitive diagnostic techniques.

White blood cell counts

This study usually is suggested but does not produce a specific finding.

The white blood cell (WBC) count may be normal or elevated in cases of NP or conditions that mimic NP. A shift to the left reflects the stress that the patient is being subjected to; a left shift does not imply infection versus noninfection. The degree of left shift indicates the degree of stress on the host.

Leukocytosis versus a normal WBC count does not favor the diagnosis of NP over the diseases that mimic NP because they can produce similar elevation, as well.

Obtain blood cultures as early as possible to retrospectively diagnose hematogenous pathogens.

Imaging Studies:

Obtain serial chest x-rays to assist in evaluating the progress of the pneumonia and the efficacy of appropriate antimicrobial therapy.

X-rays also may distinguish various mimics from actual NP. In these patients, performing a CT scan or spiral CT scan may be useful.

Other Tests:

Obtain ECGs and ventilation-perfusion scans should eliminate pneumonia mimics. ECGs, cardiac enzymes, and Swan-Ganz readings may rule out left ventricular failure caused by exacerbation of heart failure or new myocardial infarction.

Obtain other tests that are related to the possible underlying causes of the pulmonary infiltrates; for example, if suspecting lupus pneumonitis in a patient, inquire about a history of SLE pneumonitis, and then perform serological tests to diagnose SLE.

Tests such as that for arterial blood gas (ABG) merely assess the degree of severity of lung dysfunction but are not useful in diagnosing NP. Obtain ABGs to help diagnose a diffusion defect related to interstitial lung diseases.

Procedures:

Bronchoscopic techniques

These techniques vary considerably in their sensitivity and specificity, and the literature usually quotes high-end numbers. In fact, bronchoscopically obtained specimens of respiratory secretions sent to the laboratory for semiquantitative bacterial cell counts are indirect approximations, at best, and reflect airway colonization rather than parenchymal lung invasion. Since all bronchoscopic techniques, even those using protective sampling techniques, do not differentiate colonization from infection, the finding of multiple organisms via bronchoscopic techniques is diagnostic of airway colonization. The recovery of multiple organisms or nonpulmonary pathogens collected from intubated patients via bronchoscopic techniques is proof of specimen contamination from the lower airways.

Dismissing certain organisms recovered from respiratory secretions is helpful, because they never cause NP or any other kind of pneumonia. These organisms include Citrobacter, Flavobacterium, Enterobacter, Stenotrophomonas maltophilia, Burkholderia cepacia, S aureus, Enterococcus, and Candida species.

Physicians place undue reliance on bronchoscopic techniques, which sample the flora of the distal airway but do not reflect the microbiology causing lung infection.

Perform a percutaneous fine-needle biopsy of the involved area of the lung to provide a tissue-based diagnosis with correct microbiological identification (excluding culture contaminants from the source of the specimen). This procedure is relatively safe and is underutilized as a diagnostic procedure.

Histologic Findings: Histologic study of lung tissue reveals either necrotizing pneumonia or nonnecrotizing pneumonia, depending upon the pathogen. P aeruginosa produces a necrotizing pneumonia with vessel invasion, local hemorrhage, and microabscess formation. Other aerobic gram-negative bacilli produce a polymorphonuclear response at the site of invasion, but microabscess formation and vessel invasion are not present.

TREATMENT Section 6 of 11

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Medical Care:

Table 2. Principles of Appropriate Empiric Antibiotic Coverage In Nosocomial Pneumonias

Pathogens	Comments
Direct empiric coverage against common nosocomial pathogens P aeruginosa Klebsiella E coli	Direct coverage against P aeruginosa, which also covers other NP pathogens.
Do not add coverage to cover nonnosocomial pulmonary pathogens or S aureus (MSSA/MRSA).	Do not add vancomycin to NP regimens. Vancomycin to cover S aureus (MSSA/MRSA) is unnecessary and predisposes to the emergence of vancomycin-resistant enterococcus (VRE).
Serratia	Pathogen rarely causes NP but is covered regardless with anti–P aeruginosa coverage
Enterobacter Stenotrophomonas (formerly Pseudomonas) maltophilia Burkholderia (formerly Pseudomonas) cepacia	Enterobacter does not cause NP. S maltophilia or B cepacia are common colonizers of respiratory secretions, do not cause NP, and are potential pathogens only in patients with bronchiectasis or cystic fibrosis.
Oropharyngeal anaerobes	These pathogens are unimportant from a therapeutic standpoint.

Table 3. Empiric monotherapy versus combination therapy
Therapy Comments
Optimal empiric monotherapy for NP
Cefepime
or
Meropenem
or
Piperacillin
Avoid monotherapy with ciprofloxacin, ceftazidime, or imipenem because they are likely to induce resistance potential.

Optimal combination regimens for proven P aeruginosa NP

Cefepime or Meropenem
plus plus
Levofloxacin Levofloxacin
or or
Aztreonam Aztreonam
or or
Amikacin Amikacin
or or
Piperacillin Piperacillin
Avoid using ciprofloxacin, ceftazidime, gentamicin, or imipenem in combination regimens, because combination therapy does not eliminate the resistance potential of these antibiotics.

If selecting an aminoglycoside for combination therapy regimen, use amikacin or tobramycin once daily in preference to gentamicin, to avoid resistance problems.

If selecting a quinolone in a combination therapy regimen, use levofloxacin, which has very good anti–P aeruginosa activity (equal to ciprofloxacin in anti–P aeruginosa combination regimens, but less than ciprofloxacin if used alone).

Patients with NP usually require ventilatory support at some time and usually need supplemental oxygen therapy.

Turning the patient while he or she is in bed may help reduce the incidence of NP.
Medications

Before embarking on empiric antimicrobial therapy, try to eliminate the mimics of NP by ruling out these conditions. If the mimics of NP can be ruled out with a reasonable degree of certainty, then empiric therapy for NP is appropriate.

The precise pathogen that causes NP usually is unknown. Empiric antimicrobial therapy is the only practical approach. Provide monotherapy with any anti–P aeruginosa coverage because it is just as effective as combination regimens; therefore, empiric monotherapy using an agent with a high degree of activity against P aeruginosa also is effective against all other aerobic gram-negative bacillary pathogens. Coverage against oral anaerobes and S aureus is not necessary.

If suspecting P aeruginosa on the basis of chest x-ray findings (eg, necrotizing pneumonia with elastin fibers in the sputum, rapid cavitation on the chest x-ray in 72 h or less), the addition of antipseudomonal therapy may be appropriate. Do not consider P aeruginosa pneumonia in NP patients simply because it is cultured from respiratory secretions regardless of the bronchoscope technique used. If the patient has pulmonary infiltrates, purulent secretions, and cultured P aeruginosa from respiratory secretions but no rapid cavitation on the chest x-ray, then suspect Pseudomonas tracheobronchitis and not pseudomonal NP.

For pseudomonal NP, physicians prefer double-drug coverage, using agents with a high degree of antipseudomonal activity and a low resistance potential. Optimal combinations include cefepime plus levofloxacin, aztreonam, meropenem, or aminoglycoside. Alternately, using antipseudomonal penicillin (eg, piperacillin) in combination with levofloxacin, meropenem, aminoglycoside, or aztreonam, may provide equal efficacy.

Consultations:

Infectious disease specialist to assess the microbiology of specimens obtained from the patient, to rule out the mimics of NP, and to give empiric or specific empirical antimicrobial therapy

Pulmonologist to help with mechanical ventilation (often required in patients with NP)

Other consultations

Rheumatologist if patient appears to have lupus or SLE pneumonitis

Cardiologist if patient has heart failure

Oncology consultation prudent for possible pulmonary infiltrates caused by a lymphangitic spread of a malignancy

Diet:

Most patients are intubated and are instructed to receive nothing by mouth (NPO).

Activity:

Most patients are intubated and are limited to bed rest.

MEDICATION

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Ordinarily, treat NP for 14 days. If the patient indeed has NP and the appropriate antimicrobial therapy is administered, significant improvement in the pulmonary infiltrate shows in the chest x-ray during the 2 weeks of antimicrobial therapy. If the pulmonary infiltrates are unchanged after a 2-week course of therapy, then suspect that the infiltrates are not infectious in origin. Start a diagnostic workup to consider other infectious diseases that do not respond to antibiotics (eg, herpesvirus type 1 [HSV-1] pneumonitis) or that have noninfectious disease etiologies (eg, bronchogenic carcinomas).

Further Inpatient Care:

Transfer patients to the ICU if they are on the general medical wards and cannot be maintained without ventilatory support.

Patients in the ICU may require ventilatory support, depending on their respiratory status.

Deterrence/Prevention:

The incidence of NP may decrease with the use of beds that permit some degree of patient turning.

Complications:

The differential diagnosis is the main clinical problem with NP. Many conditions mimic the presentation of NP. One example is any disorder suggesting that the patient may have leukocytosis with variable degrees of left shift. An inflammatory or infectious process can cause fever; therefore, do not regard this symptom as an indicator for an infectious disease process. Many conditions can cause pulmonary infiltrates other than NP. Consider all of these differentials carefully before diagnosing the patient and embarking on a course of antimicrobial therapy.

Failure to successfully wean the patient from the respirator is a common problem following intubation for NP. Failure to wean the patient from the respirator may be from a lack of cardiopulmonary function or a superimposed process (eg, HSV-1 pneumonitis).

HSV-1 pneumonitis presents in intubated patients who have unchanging or persistent pulmonary infiltrates after 2 weeks of antimicrobial therapy. These patients usually have low-grade fevers with variable degrees of leukocytosis. Demonstrating HSV-1 in samples of respiratory secretions may make the diagnosis.

Start treatment with acyclovir in patients diagnosed with HSV-1; acyclovir decreases hypoxemia and subsequently permits weaning of the patient from the respirator.

Prognosis:

Patient prognosis depends on preexisting underlying cardiopulmonary function and host defenses.

MISCELLANEOUS

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Medical/Legal Pitfalls:

Failure to direct empiric monotherapy against P aeruginosa ensuring coverage against all other bacteriologic causes of NP

Failure to consider the numerous conditions that mimic NP, many of which are treatable and reversible disorders

Failure to consider the most common conditions that mimic NP, which include pulmonary hemorrhage, pulmonary embolus, and congestive heart failure

Failure to suspect ARDS, which usually is readily diagnosable according to the microatelectatic changes on the chest x-ray and the progressive and severe hypoxemia by ABGs; little or no fever may accompany these symptoms

Special Concerns:

Patients may further decrease the cardiopulmonary reserve of pneumonia with compromised cardiac and lung function, which accounts for the high mortality and morbidity.

Barotrauma may decrease an already compromised lung function and alter chest x-ray appearances.

PICTURES

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Caption: Picture 1. Typical chest x-ray of a patient with nosocomial pneumonia
Click to see detail View Full Size Image

Picture Type: X-RAY

BIBLIOGRAPHY Section 11 of 11

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Nosocomial Pneumonia excerpt