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Nosocomial pneumonia 

Nosocomial pneumonia

Chapter:
Nosocomial pneumonia
Author(s):

John G. Bartlett

DOI:
10.1093/med/9780199204854.003.180403
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Essentials

Nosocomial pneumonia is generally defined as a new pulmonary infiltrate on chest radiography, combined with evidence of infection expressed as fever, purulent respiratory secretions and/or leucocytosis, with onset at least 72 h after admission. It is the most frequent lethal nosocomial infection (overall mortality 8 to 20%).

Aetiology—most cases are caused by Gram-negative bacteria (50–70%) or Staphylococcus aureus (20–30%). Gram-negative bacteria reach the lung by aspiration of gastric contents or by microaspiration of upper airway secretions, throat cultures revealing that 60 to 70% of patients on intensive care units are colonized by these organisms (compared to 2–3% of healthy people).

Prevention—the best proven methods of prevention are by nursing the patient in the semi-upright position to reduce the risk of aspiration, and hand washing between patients to prevent transmission of nosocomial pathogens.

Diagnosis—this is often straightforward: due to easy access to cultures from tracheal aspirates and the ease of growing likely pathogens.

Management—when empirical decisions are necessary in seriously ill patients, the favoured drugs directed against Gram-negative bacteria are ceftazidime, cefepime, imipenem/meropenem, doripenem, piperacillin/piperacillin–tazobactam, ticarcillin/ticarcillin–sulbactam, or ciprofloxacin. For S. aureus, vancomycin or linezolid is added.

Introduction

Nosocomial pneumonia is generally defined as a new pulmonary infiltrate on chest radiography, combined with evidence of infection expressed as fever, purulent respiratory secretions, and/or leucocytosis, with onset at least 72 h after admission, but despite the standard use of this definition, quantitative bronchoscopic specimens confirm an infection in only about half of the cases. Although these infections account for only about 15% of all nosocomial infections, they are the most frequent, lethal, nosocomial infection. The bacteriology and management are different from community-acquired infections of the lung (see Chapter 18.4.2).

Aetiology

Gram-negative bacteria account for 50 to 70% of cases; other pathogens include Staphylococcus aureus in 20 to 30% of cases; less common are anaerobic bacteria, Haemophilus influenzae, and Streptococcus pneumoniae (Table 18.4.3.1). Legionella accounts for about 1 to 2% of all nosocomial pneumonia, but the frequency may be much higher when it is epidemic or endemic within a hospital. Viruses are implicated in 10 to 20%—primarily influenza and respiratory syncytial virus and, in the immunocompromised host, cytomegalovirus. Tuberculosis is rare, but important to remember. Fungi are also rare, with the exception of aspergillus in selected immunocompromised patients.

Table 18.4.3.1 Microbiology of nosocomial pneumonia

Microbe

Frequency (%)

Bacteria

80–90

Gram-negative bacteria

50–70

Staph. aureus

15–30

Anaerobic bacteria

10–30

Haemophilus influenzae

10–20

Streptococcus pneumoniae

10–20

Legionella

4

Viral

10–20

Fungi

<1

Epidemiology

Most reports indicate that 0.5 to 1% of all hospitalized patients develop nosocomial pneumonia. The rates in intensive care units are generally higher, and among patients who are mechanically ventilated the rate is 6 to 20 times greater than for nonventilated patients. However, it should be noted that some of these incidence statistics are disputed due to the lack of precision in the diagnosis of nosocomial pneumonia. Other processes that may cause pulmonary infiltrates with variable presence of fever, purulent respiratory secretions, and/or leucocytosis include congestive heart failure, pulmonary embolism, atelectasis, adverse drug reactions, pulmonary haemorrhage, and the acute respiratory distress syndrome (ARDS).

The epidemiology of the pathogens in nosocomial pneumonia is highly variable. Some organisms become endemic, especially in intensive care units, the major pathogens in this setting being acinetobacter, extended-spectrum β‎-lactamase (ESBL)-producing klebsiella, serratia, stenotrophamonas, pseudomonas, enterobacter, and methicillin-resistant S. aureus (MRSA). Another important nosocomial pathogen is legionella, which may cause outbreaks of legionnaire’s disease in hospitals that can sometimes be traced to water supplies with distribution via air-conditioning cooling systems or shower heads. In these cases, the same species and serogroup found in the nosocomial cases should be found in the epidemiologically linked water supply. Aspergillosis may occur as epidemics among vulnerable patients with compromised cell-mediated immunity, neutropenia, or both. Influenza is highly contagious, and patients with influenza are commonly hospitalized, so it is now recommended that all patients with suspected influenza have confirmation of this diagnosis by rapid influenza testing, and the preference is for a single room when this is feasible.

Pathogenesis

The relatively high rates of pulmonary infections among patients who are hospitalized reflects (1) clustering of highly vulnerable patients; (2) patients rendered particularly vulnerable by violations of the integrity of the upper airways by intubation or tracheostomy; (3) many patients who are prone to aspiration due to compromised consciousness caused by associated medical conditions and anaesthesia; (4) patients rendered susceptible due to organ transplantation, cancer chemotherapy, and AIDS (Box 18.4.3.1).

As stated previously, the dominant pathogens in nosocomial pneumonia are Gram-negative bacteria, which reach the lung by aspiration of gastric contents or by microaspiration of upper airway secretions. The best explanation for this association between bacteriology and pathogenesis is the observation that patients with serious illness commonly have abnormal colonization of the upper airways by Gram-negative bacteria. Thus, throat cultures show that Gram-negative bacteria are found in only 2 to 3% of healthy persons, psychiatric patients, physicians, and medical students, whereas the rate of colonization in patients who are moderately ill is 30 to 40%, and in intensive care units the rate is 60 to 70%. These colonization rates are independent of antibiotic administration, but antibiotic exposure will increase the carrier rate even further. It can also be shown that buccal epithelial cells from patients who are seriously ill have enhanced attachment by Gram-negative bacteria in vitro. The frequency of positive throat cultures for Gram-negative bacteria and the number that attach to respiratory cells are directly correlated with the severity of the associated disease. The usual mechanism of Gram-negative bacillary pneumonia in most hospitalized patients is aspiration of these organisms in the upper airways, or aspiration of these organisms from gastric contents after they are swallowed.

Pathogenesis of other organisms is quite different. Legionella, tuberculosis, influenza, and aspergillus are inhaled, the usual source being environmental (legionella or aspergillus) or another patient (influenza or tuberculosis).

Clinical features

Nosocomial pneumonia Case History—A 75 yr old retired farmer with cough and fever.

The classic presentation for pneumonia is cough and fever, usually with purulent respiratory secretions. The diagnosis of pneumonia requires the demonstration of a pulmonary infiltrate on chest radiography. These same symptoms may be present in patients with acute bronchitis, which is virtually always a viral infection that does not merit antibacterial treatment. A notable exception is patients who have violation of the airways with endotracheal tubes or tracheostomies who may have ‘febrile tracheobronchitis’ due to bacterial infection, most frequently at the tip of the tube, the site of the cuff, or the site of insertion. As noted previously, many patients who satisfy the definition for nosocomial pneumonia based on a pulmonary infiltrate accompanied by fever and purulent respiratory secretions have alternative diagnoses when studied by reliable microbiological techniques using bronchoscopy with quantitative cultures of a bronchial-protected brush or bronchoalveolar lavage (BAL). The alternative noninfectious conditions in culture-negative cases include congestive heart failure, pulmonary embolism, atelectasis, bronchiolitis obliterans organizing pneumonia, etc.

Laboratory diagnosis

Tests to establish diagnosis and evaluate severity

The chest radiograph is critical for the confirmation of pneumonia. Major causes of false negative radiographs in the presence of nosocomial pneumonia are severe neutropenia and pneumonia caused by P. jirovecii. CT scans may reveal infiltrates that are not present on plain films, but it is not clear that this distinguishes a group that requires antibiotic treatment. Thus, the chest radiograph is generally viewed as adequately sensitive for detection of nosocomial pneumonia.

It is important to monitor blood gases to determine severity of illness and to monitor respiratory support.

Studies to determine microbial aetiology

Blood cultures are positive in 2 to 6% of patients with nosocomial pneumonia and clearly identify the causative agent. Some patients will have empyemas, and thoracentesis is necessary for both diagnosis and treatment. Again, this represents an uncontaminated source for culture, providing definitive evidence of the responsible pathogen. Empyema is an infrequent complication of nosocomial pneumonia, except in patients who have undergone thoracotomy who often have an empyema as a complication of chest tube placement.

Legionella, Mycobacterium tuberculosis, and respiratory viruses (influenza, parainfluenza, and respiratory syncytial virus) represent definitive pathogens when recovered in respiratory specimens since these organisms do not colonize the normal respiratory tract.

Most patients with nosocomial pneumonia do not have bacteraemia, empyema, or the pathogens that do not colonize the normal airway. In these cases, the physician must usually rely on routine bacterial cultures of respiratory secretions or resort to invasive diagnostic tests using bronchoscopy with quantitative cultures of BAL specimens or of the protected brush. Multiple studies have tested the validity of these techniques for distinguishing contaminants and pathogens. The results are somewhat variable, but often dependent on the precision of methodology. However, the use of these techniques has resulted in substantial controversy in the management of nosocomial pneumonia, especially in intensive care units where the stakes are high due to high rates of resistant pathogens and mortality. Arguments in favour of invasive diagnostic studies with bronchoscopy are the facts that the technology is well studied, about one-half of patients with suspected pneumonia have negative results and antibiotics can be avoided in this population, and the clear definition of pathogens permits pathogen-specific antibiotic treatment. Others argue that the invasive methods are unrealistic or unnecessary because routine semi-quantitative cultures of sputum or endotracheal aspirates are adequate semiquantitative cultures of tracheal aspirates are cheap, easy, and provide information that is equally valid.

Regardless of the method to obtain respiratory secretions for microbiological studies, it is usually beneficial to examine the specimen cytologically. Cultures should be reported with either quantitative or semiquantitative results. For quantitative results, the usual threshold for significance with the protected brush is 103/ml, and for BAL specimens it is usually 103 or 104/ml. With semiquantitative techniques, moderate or heavy growth usually indicates ‘significant concentrations.’ The main pathogens are summarized in Table 18.4.3.1: S. epidermidis, diphtheroids, H. parainfluenzae, enterococcus, and α‎-haemolytic streptococci are generally regarded as contaminants, regardless of concentrations. Anaerobic bacteria are frequently neglected pulmonary pathogens, but it is difficult to obtain specimens valid for anaerobic cultures, and many laboratories struggle with anaerobic microbiology even when the right specimens are obtained. The diagnosis of anaerobic pneumonia should be suspected when Gram stains show mixed bacteria, especially when there are morphotypes suggesting anaerobes, and specimens obtained by tracheal aspirate or bronchoscopy should be examined for these organisms. Putrid drainage always indicates anaerobic infection.

Treatment

The main management issues are antibiotic selection and respiratory support. The optimal method for selection of antibiotics is to base this decision on results of Gram stains and cultures (Table 18.4.3.2). When empirical decisions are necessary in seriously ill patients, agents are directed against Gram-negative bacteria, and the favoured drugs in this context are ceftazidime, cefepime, imipenem/meropenem, doripenem, piperacillin/piperacillin–tazobactam, ticarcillin/ticarcillin–sulbactam, or ciprofloxacin. For S. aureus, vancomycin is often added on the basis of Gram stain results or the perceived need to cover this pathogen. Some experts prefer linezolid for pneumonia involving MRSA, based on better lung penetration compared to vancomycin and limited clinical data favouring this drug.

Table 18.4.3.2 Treatment of nosocomial pneumonia

Pathogen

Antibiotic

Bacteria

Gram-negative bacilli

Pseudomonas aeruginosaa

Ceftazidime, imipenem, meropenem, doripenem, piperacillin/ticarcillin, cefepime or aztreonam, plus ciprofloxacin or an aminoglycoside

Xanthomonasa

Trimethoprim–sulfa

Enterobacteriaceaea

Cephalosporin (2nd or 3rd generation), β‎-lactam–β‎-lactamase inhibitor, aztreonam, imipenem, fluoroquinolone ± aminoglycoside

Anaerobes

Imipenem, β‎-lactam–β‎-lactamase inhibitor, clindamycin

Staphylococcus aureusa

Vancomycin or linezolid

Legionella

Gatifloxacin, levofloxacin, or azithromycin + rifampin

Viruses

Influenza

Oseltamivir or zanamivir

Fungi

Aspergillus

Voriconazole

a Need in vitro susceptibility data.

Treatment for Pseudomonas aeruginosa, Acinetobacter, Klebsiella and other GNB are the predominant Gram-negative bacilli in nosocomial pneumonia in intensive care units, should be based on in vitro sensitivity tests. Anaerobic bacteria are well treated with imipenem/meropenem or any β‎-lactam–β‎-lactamase inhibitor; clindamycin can be used if these organisms are suspected and the alternatives are not used for other pathogens. The role of aminoglycosides in pulmonary infections involving Gram-negative bacilli is controversial due to the availability of effective less toxic alternatives. S. aureus, especially MRSA is also very important. The preferred antibiotics for MRSA in the lung are vancomycin or linezolide.

It should be emphasized that cultures of respiratory secretions obtained after the inception of antibiotic treatment have reduced validity. This observation emphasizes the importance of pretreatment cultures and caution with therapeutic decisions based on post-treatment cultures other than those of blood and pleural fluid.

Outcome

Nosocomial pneumonia is associated with a mortality rate reported at 8 to 20% for all cases. The mortality rate for infections acquired in the intensive care unit is 20 to 40%, with a mean of 25%. In the latter group the attributable mortality is 30 to 33%, meaning that associated conditions are the major factors in causing death.

Prevention

The frequency of nosocomial pneumonia and high mortality rate, especially in intensive care units, has prompted extensive studies of prevention. The methods that have withstood the test of time and have proven meritorious are the use of the semi-upright position to reduce the risk of aspiration, and hand washing between patients to prevent transmission of nosocomial pathogens.

The concern for patient positioning is based on marker studies showing that stomach contents are displaced to the lower respiratory tract with high frequency in patients in the recumbent position, and this can be easily corrected by use of an upright or semi-upright position. The assumption is that nosocomial pneumonia is frequently due to bacteria that reside in the stomach as a result of oral colonization.

Hand washing is a time-honoured method to reduce nosocomial infection that is commonly neglected by hospital personnel. It appears to be particularly important in the transmission of S. aureus, and is often important in organisms that are endemic or epidemic within hospital units such as acinetobacter, serratia, xanthomonas, pseudomonas, and enterobacter.

Other preventive measures are the use of orotracheal tubes instead of nasotracheal tubes, avoidance of intubation, maintenance of tube cuff pressure at more than 20 cm H2O, and possibly the selective use of sulcrafate to reduce gastrointestinal bleeding.

A common practice in some intensive care units is ‘selective decontamination’ to interrupt the cycle of colonization of the colon by Gram-negative bacteria, followed by colonization of the upper airways by the same organisms, and then aspiration to cause pneumonia. The goal of selective decontamination is elimination or reduction in Gram-negative bacteria in the gastrointestinal tract with antibiotics that also preserve the anaerobic bacteria in the flora, since these are largely responsible for microbial population control in the colon. Drugs that are commonly used are oral preparations of polymyxin, aminoglycosides, aztreonam, trimethoprim–sulfamethoxazole, or cephalosporins. These are given orally with the expectation that they will have a substantial impact on the colonic flora, and they are sometimes also incorporated into paste formulations for application to the upper airways as well. Extensive trials with selective decontamination show that they achieve a substantial reduction in nosocomial pneumonia, but they do not seem to influence mortality due to this condition. Major concerns are the failure to reduce mortality rates, excessive costs of the regimens, and the perception of antibiotic abuse with encouragement of resistance.

Topical antibiotics have also been tested for utility in prophylaxis. The method is installation of drugs (usually polymyxin or aminoglycosides) through tracheostomies, endotracheal tubes, or by aerosolization. Extensive therapeutic trials with this tactic have shown that it is sometimes successful in interrupting epidemics due to susceptible bacteria, especially P. aeruginosa, but mortality rates have generally remained unchanged, and there is concern about the evolution of resistant bacteria. Topical antibiotics are generally not recommended, except for some patients with cystic fibrosis.

Interruption of epidemics involving legionella and aspergillus requires different tactics because these organisms are inhaled. For legionella and aspergillus, the goal is to eliminate the environmental source. Influenza is transmitted from person-to-person, so the goal is to eliminate this type of contact, which must include removal of health care workers with influenza from jobs that require patient contact. All hospital personnel should have influenza vaccine as a method to protect patients, and hospital personnel with jobs that require patient contact must be furloughed if they have suspected or established influenza.

Further reading

American Thoracic Society (2005). Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy and preventative strategies. A consensus statement. Am J Respir Crit Care Med, 171, 388–416.Find this resource:

    Canadian Critical Care Trials Group (2006). A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med, 355, 2619–30.Find this resource:

    Fagon JY, et al. (1988). Detection of nosocomial lung infection in ventilated patients: use of a protected specimen brush and quantitative culture techniques in 147 patients. Am Rev Respir Dis, 138, 110–16.Find this resource:

    Fagon JY, et al. (1996). Nosocomial pneumonia and mortality among patients in intensive care units. JAMA, 275, 866–9.Find this resource:

    Fagon JY, et al. (2000). Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia. Ann Intern Med, 132, 621–30.Find this resource:

    Johanson WG, Pierce AK, Sanford JP (1969). Changing pharyngeal bacterial flora of hospitalized patients: emergence of Gram-negative bacilli. N Engl J Med, 281, 1137–40.Find this resource:

    Johanson WG Jr, Woods DE, Chaudhuri T (1979). Association of respiratory tract colonization with adherence of Gram-negative bacilli to epithelial cells. J Infect Dis, 139, 667–73.Find this resource:

    Morehead RS, Pinto SJ (2000). Ventilator-associated pneumonia. Arch Intern Med, 160, 1926–36.Find this resource: