Nosocomial and Healthcare-Associated Pneumonia
- Author: Burke A Cunha, MD; Chief Editor: John L Brusch, MD, FACP more...
Nosocomial pneumonia (NP) clinically presents more than 7 days after hospitalization with new fever, pulmonary infiltrates, and leukocytosis. Clinicians should understand that these findings are often present with mimics of nosocomial pneumonia, such as congestive heart failure (CHF), pulmonary emboli, pulmonary hemorrhage, primary or metastatic lung carcinomas, leukemias/lymphomas, pulmonary drug reactions, or radiation pneumonitis, among others. So-called “early nosocomial pneumonia” cases occurring less than 3 days after admission, are, in fact, community-acquired pneumonia (CAP) manifesting early after hospital admission. Ventilator-associated pneumonia (VAP) refers to patients on ventilators who develop nosocomial pneumonia.
Nosocomial pneumonia is a common nosocomial bacterial infection and is most prevalent in medical and surgical intensive care units (ICUs). Nosocomial pneumonia adds significantly to the cost of hospital care and to the length of hospital stays.
Patients with nosocomial pneumonia develop fever and leukocytosis, and these findings are a requisite for the presumptive diagnosis of nosocomial pneumonia. Respiratory tract symptoms include an increase in respiratory rate and shortness of breath.
Inhalation, aspiration, and hematogenous spread are the 3 main mechanisms by which bacteria reach the lungs. The primary route through which organisms enter the lower airways is via aspiration of oropharyngeal secretions into the trachea.
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 is due to the aspiration of colonized upper respiratory tract secretions.
The stomach appears to be an important reservoir of gram-negative bacilli that can ascend and colonize the respiratory tract. A prospective observational study found that patients who used acid-suppressive medications were more likely to develop hospital-acquired pneumonia than were patients who did not (5% vs 2%). The risk for pneumonia was significantly increased with proton pump inhibitors, but not with histamine 2–blocking agents.
Hematogenously acquired infections originate from a distant source and reach the lungs via the bloodstream.
The development of nosocomial pneumonia represents an imbalance between normal host defenses and the ability of microorganisms to colonize and then invade the lower respiratory tract.
Because aerobic gram-negative bacilli (eg, Pseudomonas aeruginosa) are the major pathogens associated with nosocomial pneumonia, the pathophysiology of nosocomial pneumonia relates to the destructive effect on lung tissue. Aerobic gram-negative pathogens may be divided into 2 categories. The first category includes organisms that cause necrotizing pneumonia with rapid cavitation, microabscess formation, blood-vessel invasion, and hemorrhage (eg, P aeruginosa). Alternatively, other nonnecrotizing gram-negative bacilli (eg, Serratia marcescens) may be responsible for nosocomial pneumonia.
Common causes of nosocomial pneumonia
Common bacteria involved in nosocomial pneumonia include the following:
Acinetobacter species commonly colonize respiratory tract secretions in patients in the ICU. Acinetobacter nosocomial pneumonia occurs in clusters/outbreaks and not as isolated cases.
Streptococcus pneumoniae and Haemophilus influenzae are the main pathogens in early-onset hospital-acquired pneumonia.
Less-common pathogens associated with nosocomial pneumonia
The following are less-common pathogens implicated in nosocomial pneumonia clusters/outbreaks:
Respiratory syncytial virus (RSV)
Human parainfluenza virus 3 (HPIV-3)
Human metapneumovirus (hMPV)
Nosocomial Legionella pneumonia occurs only in outbreaks or clusters.
Influenza A, RSV, hMPV, or HPIV-3 may cause hospital-acquired pneumonia from person-to-person spread.
Unusual causes of nosocomial pneumonia
The following rarely, if ever, cause nosocomial pneumonia:
Stenotrophomonas maltophilia (formerly Pseudomonas maltophilia)
Burkholderia cepacia (formerly Pseudomonas cepacia)
Staphylococcus aureus, including methicillin-susceptible S aureus (MSSA) and methicillin-resistant S aureus (MRSA)
These organisms are commonly recovered from respiratory secretions in patients with ventilator-associated pneumonia. The recovery of a respiratory pathogen from respiratory secretions does not establish it as the cause of nosocomial pneumonia. MSSA/MRSA frequently colonize respiratory secretions in intubated patients but rarely, if ever, cause nosocomial pneumonia/ventilator-associated pneumonia. In contrast, MSSA/MRSA may cause community-acquired pneumonia (CAP) in those with influenza. Anaerobic organisms are not important pathogens in nosocomial pneumonia. (See Differentials in Nosocomial Pneumonia.)
As previously mentioned, the stomach appears to be an important reservoir of gram-negative bacilli that can ascend and colonize the respiratory tract. A prospective observational study found that patients who used acid-suppressive medications were more likely to develop hospital-acquired pneumonia than were patients who did not (5% vs 2%).
Further evaluation by drug class showed that the risk for pneumonia was significantly increased with proton pump inhibitors, but not with histamine 2–blocking agents.
Epidemiology of Nosocomial Pneumonia
Incidence in the United States
Nosocomial pneumonia is the most common cause of death among all hospital-acquired infections, with mortality rates of up to 33%. It is common in individuals undergoing mechanical ventilation but can also develop in nonventilated patients.
The international incidence and prevalence of nosocomial pneumonia is similar to that in the United States, with comparable rates of responsible microorganisms.
Race and sex predilections
Nosocomial pneumonia has no race or sex predilection
Nosocomial pneumonia is most common in elderly patients; however, patients of any age may be affected.
Morbidity and mortality in nosocomial pneumonia
Intubation and ventilatory support bypass the normal host defense mechanisms, predisposing patients with nosocomial pneumonia to infection.
In addition, nosocomial pneumonia that develops in ICU patients is associated with high morbidity and mortality rates, because these patients are already critically ill.
Compromised cardiac and lung function may further decrease their cardiopulmonary reserve.
Ventilator-associated barotrauma often decreases already compromised lung function. In addition, it may alter chest radiographic appearances.
As mentioned above, early-onset nosocomial pneumonia (ie, hospital onset of CAP) expectedly has a better prognosis than late-onset nosocomial pneumonia because the latter tends to be associated with multidrug-resistant organisms.[5, 6, 7, 8, 9]
The prognosis in patients with nosocomial pneumonia depends primarily on preexisting underlying cardiopulmonary function and host defenses.
Differentials in Nosocomial Pneumonia
All patients with presumed nosocomial pneumonia should undergo testing to rule out conditions that mimic nosocomial pneumonia. The diagnosis of nosocomial pneumonia is difficult because it may present in a very nonspecific fashion. A summary of management strategies is available through a practice guideline provided by the ATS.
The wide list of differential diagnoses presents a major challenge in diagnosing nosocomial pneumonia. Many conditions other than nosocomial pneumonia mimic pulmonary infiltrates (eg, fluid, atelectasis) on chest radiographs.
Any disorder that results in leukocytosis with variable degrees of left shift may be included in the differential diagnoses. Noninfectious inflammation may produce fever.
Consider all of these differential diagnoses carefully before settling on a diagnosis and embarking on a course of antimicrobial therapy.
The most common causes of infiltrates in ventilated patients with fever and/or leukocytosis include the following conditions:
Pulmonary embolus or infarction
Pulmonary drug reactions
Collagen vascular diseases
Bronchiolitis obliterans-organizing pneumonia (BOOP)
Collagen-vascular diseases (eg, systemic lupus erythematosus [SLE])
Interstitial lung disease
ARDS is usually readily diagnosable based on the appearance of small lung volumes due to microatelectatic changes on the chest radiograph and the progressive and severe hypoxemia. Little or no fever accompanies ARDS, unless it is due to acute pancreatitis.
In most cases, the diagnosis of nosocomial pneumonia is clinical and, unlike CAP, is not diagnosed based on respiratory secretion cultures. Semiquantitative cultures from bronchoalveolar lavage (BAL) samples may be helpful. The definitive diagnosis of nosocomial pneumonia rests on tissue biopsy, which is rarely performed. Therefore, the clinician must evaluate various findings that are not specific to nosocomial pneumonia, including the following:
Elevated white blood cell (WBC) count
New or worsening pulmonary infiltrate compatible with a bacterial pneumonia
See Differentials in Nosocomial Pneumonia.
Physical findings in nosocomial pneumonia relate to the pneumonia’s distribution in the chest. Physically, lobar lesions caused by nosocomial pneumonia mimic those caused by any other type of pneumonia (eg, rales in the location of the pneumonic process).
White Blood Cell Count and Blood Cultures
The WBC count may be normal or elevated in nosocomial pneumonia or disorders that mimic nosocomial pneumonia/ventilator-associated pneumonia. A left shift reflects the stress and neither rules out nor confirms infection. The degree of left shift indicates the degree of stress in the host. Neither leukocytosis nor a normal WBC count favors the diagnosis of nosocomial pneumonia over the diseases that mimic nosocomial pneumonia, as these can produce similar elevations.
Obtain blood cultures as early as possible, although they are infrequently positive, except in cases of hematogenous nosocomial pneumonia. The recovery of MSSA/MRSA in blood cultures in patients with nosocomial pneumonia/ventilator-associated pneumonia without the clinical findings of MSSA/MRSA pneumonia (eg, rapid cavitation, high fevers, cyanosis) is likely due to skin contamination of blood cultures.
Obtain serial chest radiographs to assist in evaluating the progress of the pneumonia and the efficacy of appropriate antimicrobial therapy. (See the image below.)
Computed tomography (CT) scanning or spiral CT scanning may be useful in differentiating mimics from actual nosocomial pneumonia. For example blood cultures that are positive for MSSA/MRSA in a febrile intubated patient are not diagnostic of MSSA/MRSA nosocomial pneumonia/ventilator-associated pneumonia. The diagnosis of MSSA/MRSA community-acquired pneumonia/nosocomial pneumonia is based on the clinical presence of fever, cyanosis, hypotension, and rapid cavitation of infiltrates (<72 hours) on chest radiographs plus MSSA/MRSA in respiratory secretions.
These techniques have variable sensitivities and specificities, although there are accepted criteria for semiquantitative cultures to improve the diagnostic reliability of bronchoscopically derived cultures.
Even protected brush/cultures from bronchoalveolar lavage (BAL) reflect airway colonization (eg, Aspergillus, MSSA/MRSA, P aeruginosa) rather than nosocomial pneumonia/ventilator-associated pneumonia pathogens in the lung parenchyma.
Multiple organisms as a cause of nosocomial pneumonia
Multiple pathogens obtained via nontissue biopsy culture methods usually indicate lower airway colonization.
Histologic study of lung tissue reveals either necrotizing or nonnecrotizing pneumonia, depending on 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 absent.
Electrocardiograms (ECGs) and ventilation-perfusion scans help to 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 lupus pneumonitis is suspected, ask the patient about a history of SLE pneumonitis. Afterward, serologic tests should be performed to assess for SLE.
ABG studies are useful in assessing the degree of severity of lung dysfunction but not in determining the specific etiology. In general, bacterial nosocomial pneumonia/ventilator-associated pneumonias have low A-a gradients (<35).
The biomarker procalcitonin (PCT) is usually unhelpful in the diagnosis of nosocomial pneumonia in ICU patients, who often have elevated PCT levels due to hypotension, renal failure, hepatic insufficiency, pancreatitis, drug reactions, or lung cancer, among others.[11, 12]
Most patients with nosocomial pneumonia require ventilatory support at some point; the majority of patients need supplemental oxygen therapy as well. Patients with nosocomial pneumonia should be transferred to the ICU if they are on the general medical wards and cannot be maintained without ventilatory support.
Traditionally, nosocomial pneumonias have been treated for 7-14 days. However, ventilator-associated pneumonia (except due to nonfermenting gram-negative rods [eg, P aeruginosa]) can be successfully treated in 7 days. If the patient receives appropriate antimicrobial therapy for 2 weeks and does not respond (ie, improved infiltrates findings on chest radiograph), initiate a diagnostic workup to detect nonbacterial infections (eg, herpesvirus type 1 [HSV-1] pneumonitis) or noninfectious disease mimics (eg, bronchogenic carcinomas).
The specific pathogen that causes a given case of nosocomial pneumonia is usually unknown. Therefore, empiric antimicrobial therapy is the only practical approach. Delaying therapy until the pathogen is identified is not recommended. For empiric coverage of nosocomial pneumonia, monotherapy directed against P aeruginosa (also effective against other gram-negative bacilli causes of nosocomial pneumonia/ventilator-associated pneumonia), is as effective as combination therapy for nosocomial pneumonia.
For proven P aeruginosa nosocomial pneumonia, double drug coverage with a high degree of antipseudomonal activity and a low resistance potential should be used. Optimal combinations include meropenem or doripenem plus either levofloxacin or aztreonam or amikacin.
Depending on the resistance potential of the antibiotic selected, prolonged antimicrobial use is associated with an increased risk of subsequent multidrug resistance.
Principles of appropriate empiric antibiotic coverage in nosocomial pneumonias
Direct empiric coverage against common nosocomial pathogens P aeruginosa, Klebsiella species, E coli. Coverage against P aeruginosa also covers other nosocomial pneumonia pathogens.
An important caveat is that it is not difficult to differentiate P aeruginosa colonization (lacks clinical findings of P aeruginosa nosocomial pneumonia/ventilator-associated pneumonia) from P aeruginosa nosocomial pneumonia/ventilator-associated pneumonia. P aeruginosa nosocomial pneumonia/ventilator-associated pneumonia, like MSSA/MRSA nosocomial pneumonia/ventilator-associated pneumonia, is accompanied by fever, cyanosis, hypotension, and rapid cavitation (<72 hours) on chest radiography.
Enterobacter species do not cause nosocomial pneumonia. S maltophilia and B cepacia are common colonizers of respiratory secretions, but they rarely, if ever, cause nosocomial pneumonia in otherwise healthy hosts. However, they are colonizers/potential pathogens in patients with bronchiectasis or cystic fibrosis.
S aureus (MSSA/MRSA) commonly colonizes respiratory secretions (30%-50%) but rarely, if ever, causes necrotizing cavity nosocomial pneumonia. Oropharyngeal anaerobes are unimportant from a therapeutic standpoint.
Empiric monotherapy versus combination therapy
The optimal empiric monotherapy for nosocomial pneumonia consists of cefepime, meropenem, aztreonam, or levofloxacin (750-mg dose). Avoid monotherapy with ciprofloxacin, ceftazidime, or imipenem, as they are more likely to induce resistance.
Optimal combination regimens for proven P aeruginosa nosocomial pneumonia include (1) high-dose 4.5 g IV q6h piperacillin/tazobactam plus amikacin 1 g IV q24h or (2) meropenem plus levofloxacin (750-mg dose), aztreonam, or amikacin. Avoid using ciprofloxacin, ceftazidime, gentamicin, or imipenem in combination regimens, as combination therapy does not eliminate the resistance potential of these antibiotics.
When selecting an aminoglycoside for a combination therapy regimen, amikacin once daily is preferred to gentamicin or tobramycin because of enhanced anti–P aeruginosa activity and to avoid resistance. When selecting a quinolone in a combination therapy regimen, use levofloxacin at a dose of 750 mg, which has excellent anti–P aeruginosa activity (equal or better than ciprofloxacin).[5, 6, 7, 8, 9]
Multidrug resistance should be suspected in those who have received “high resistance potential” antibiotics within the preceding 90 days, if the length of the current hospitalization is 5 days of more, in immunosuppressed individuals, and when there is a high rate of antibiotic resistance either in the community or in the specific hospital. Optimal empiric therapy in this situation could include an antipseudomonal cephalosporin (cefepime), meropenem, doripenem, colistin, or amikacin.
For patients with allergies to beta-lactam antibiotics, meropenem, levofloxacin, or aztreonam may be used safely.
In nosocomial pneumonia/ventilator-associated pneumonia, outcomes depend on risk factors rather than on the initial empiric therapy.[15, 16, 17]
In patients with multidrug-resistant nosocomial pneumonia/ventilator-associated pneumonia, particularly due to extended-spectrum beta-lactamase–producing organisms, aerosolized antibiotics should be avoided, if possible. The results of studies have been inconclusive; however, aerosolized antibiotics provide low antibiotic concentrations on the surface of respiratory epithelium, which can increase resistance due to the high cross-sectional area of the lungs.
Consult an infectious disease specialist to assess the microbiology of the specimens obtained from the patient, to rule out the mimics of nosocomial pneumonia, and to administer empiric or specific empiric antimicrobial therapy.
Consult a pulmonologist to help with mechanical ventilation (often required in patients with nosocomial pneumonia).
Other consultations include the following, if indicated:
Rheumatologist (if the patient appears to have lupus or SLE pneumonitis)
Cardiologist (if the patient has heart failure)
Oncologist (for possible pulmonary infiltrates caused by a lymphangitic spread of a malignancy)
Diet, Activity, and Deterrence
Many patients with nosocomial pneumonia have significant nutritional deficiencies. Early (within 48 hours) enteral nutrition appears to decrease infectious complications. Parenteral nutrition does not seem to have this effect and should be considered only in patients with a contraindication to enteral replacement.[18, 19]
Beds that permit some degree of patient turning may decrease the likelihood of nosocomial pneumonia in at-risk patients.
Complications in Nosocomial Pneumonia
Failure to successfully wean the patient from the respirator (possibly because of a lack of cardiopulmonary function or a superimposed process [eg, HSV-1 pneumonitis]) is a common problem following intubation for nosocomial pneumonia.
HSV-1 pneumonitis develops 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 establish the diagnosis.
Start treatment with acyclovir in patients diagnosed with HSV-1 infection; acyclovir decreases hypoxemia and subsequently permits weaning of the patient from the respirator.
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