OVERVIEW
OF HEALTH CARE–ASSOCIATED PNEUMONIA, HOSPITAL-ACQUIRED PNEUMONIA,
AND VENTILATORASSOCIATED PNEUMONIA
HEALTH CARE–ASSOCIATED PNEUMONIA DEFINITIONS AND
EPIDEMIOLOGY
Health care–associated pneumonia (HCAP) refers to pneumonia in patients who have had contact with the health care environment before developing pneumonia and thus may be at risk of being colonized and infected with potentially drug-resistant pathogens. This group includes patients who have been in the hospital for at least 2 days in the past 90 days, those coming from a nursing home or extended care facility, those getting hemodialysis or home wound care, and those exposed to a family member harboring drug-resistant pathogens. Because many of these patients are at risk for infection with multidrug-resistant (MDR) gram- negative and gram-positive organisms, these patients do not have CAP, but are now defined as having HCAP. Clinical risk factors for MDR pathogens include severe pneumonia, poor functional status, recent antibiotic therapy (within the past 3 months), recent hospitalization, and immune suppression (including corticosteroid therapy).
It is important
to recognize patients with HCAP because some may have a more complex spectrum
of etiologic agents than those with community-acquired pneumonia (CAP),
including a higher mortality rate, longer length of stay, higher frequency of
aspiration, and more frequent receipt of incorrect empiric antibiotic therapy.
In this regard, patients with HCAP are similar to those with hospital-acquired
pneumonia (HAP).
HOSPITAL-ACQUIRED
PNEUMONIA AND VENTILATOR-ASSOCIATED PNEUMONIA DEFINITIONS AND EPIDEMIOLOGY
In critically
ill patients, pneumonia is the second most common intensive care unit
(ICU)–acquired infection and the one that is most likely to lead to mortality.
By definition, HAP occurs after the patient has been in the hospital for at
least 48 hours and can occur in patients who are intubated and mechanically
ventilated or in those who are not. If the patient has been intubated for at
least 48 hours and then develops pneumonia, it is termed ventilator-associated
pneumonia (VAP).
HAP occurs with
increased frequency in any patient population with impaired immune function
(either as a result of serious underlying illness or because of
therapy-associated immune dysfunction) and increased exposure of the lower
respiratory tract to bacteria (via aspiration with or without an endotracheal
tube in place). VAP is present in 20% to 50% of mechanically ventilated
patients, depending on the diagnostic criteria that are used and the risk
factors in the patient population being considered. The risk of pneumonia
increases with the duration of mechanical ventilation. Up to 40% of VAP is
early onset (in the first 5 days of hospitalization).
In addition to
mechanical ventilation, other risk factors for nosocomial pneumonia include age
older than 60 years, malnutrition (serum albumin <2.2 g/dL),
acute lung injury (acute respiratory distress syndrome), coma, burns,
recent abdominal or thoracic surgery, multiple organ failure, transfusion of
more than 4 U of blood, transport from the ICU, prior antibiotic therapy,
elevation of gastric pH (by antacids or histamine-type 2 blocking agents),
large volume aspiration, use of a nasogastric tube (rather than a tube placed
in the jejunum or a tube inserted through the mouth), use of inadequate
endotracheal tube cuff pressure (allowing aspiration of oral secretions into
the lower respiratory tract), prolonged sedation and paralysis, maintaining
patients in the supine position in bed, use of total parenteral nutrition
feeding rather than enteral feeding, and repeated reintubation.
The mortality
rate for patients with HAP can be as high as 50% to 70% in mechanically
ventilated patients. In addition, the odds ratio for mortality in patients who
acquire VAP compared with those who do not is nearly twofold, and the presence
of VAP can prolong length of stay by at least 6 to 7 days. The greatest
contributors to attributable mortality of VAP are use of an inappropriate
antibiotic therapy (one that is not active against the identified etiologic
pathogens), the presence of certain high-risk drug-resistant organisms (e.g., Pseudomonas
aeruginosa, Acinetobacter spp., or Staphylococcus aureus), and the
development of illness in a medical (rather than surgical) patient. Other
mortality risk factors for HAP include coma on admission, creatinine level
above 1.5 mg/dL, transfer from another ward to the ICU, bilateral radiographic
abnormalities, age older than 60 years, an ultimately fatal underlying
condition, shock, prior antibiotic therapy, pneumonia being a superinfection,
multiple system organ failure, and an increasing APACHE (Acute Physiology and
Chronic Health Evaluation) score during pneumonia therapy.
CAUSE AND
DIAGNOSTIC TESTING
A variety of
classification schemes for HAP are available that divide patients into
categories based on the likelihood of specific pathogens. If the patient has
earlyonset infection (within the first 5 days of hospitalization) and no risk
factors for MDR pathogens (recent hospitalization, recent antibiotic therapy,
the presence of HCAP), then the patient is likely to be infected with a group
of “core pathogens.” These include nonresistant gram-negative organisms (Escherichia coli, Klebsiella
spp., Enterobacter spp., Serratia marcescens, and Proteus spp.),
methicillin-sensitive S. aureus, and pneumococcus. On the other hand, if
the patient has late-onset infection (day 5 or later) or any of the risk
factors for MDR pathogens, then in addition to the core pathogens, the patient
is also at risk for infection with MDR gram–negative organisms such as P.
aeruginosa, Acinetobacter spp., and extended-spectrum beta-lactamase
(ESBL) producers such as Klebsiella and Enterobacter spp. or MDR
gram-positive organisms such as methicillin-resistant S. aureus (MRSA).
The diagnosis
of HAP, particularly VAP, is controversial because the clinical diagnostic
criteria are sensitive but not specific for infection. These include the finding
of a new or progressive lung infiltrate plus at least two of the following:
temperature below 36.0˚C or above 38.3˚C, leukocyte count above 10,000/mm3 or
below 5000/mm3, and purulent sputum. Another common clinical finding in patients
with pneumonia is worsening oxygenation. All of these findings are not specific
for pneumonia, so they are supplemented by microbiologic testing to define both
the presence of pneumonia and the etiologic pathogen. Although some studies
have suggested that clinical management can be improved if therapy decisions
are guided by quantitative culture data, not all studies have confirmed this
finding, and quantitative cultures are not routinely used to establish the
diagnosis of HAP and VAP.
Therapy is
initially empiric based on the likely etiologic pathogens and is generally done
with a single agent if only the core pathogens are expected, although a
broad-spectrum multidrug regimen is used if MDR pathogens are likely. After
culture data become available, therapy is focused on the organism(s) identified.
ANTIBIOTIC
RESISTANCE
When a patient
develops HAP or VAP, there is a high likelihood that the etiologic agent will
be antibiotic resistant. In fact, in patients with VAP the frequency may exceed
50% if the patient has been in the hospital for at least 7 days and has a
history of prior antibiotic use. Drug-resistant organisms are not intrinsically
more virulent than sensitive pathogens, but because their presence is often not
anticipated, the initial therapy may be incorrect, and this factor contributes
to the excess mortality associated with these organisms when they cause VAP.
MULTIDRUG-RESISTANT
GRAM-NEGATIVE ORGANISMS
Patients with
VAP are most commonly infected by gram-negative organisms, including P.
aeruginosa, Acinetobacter baumannii. K. pneumoniae, and
extended-spectrum-lactamase (ESBL)–producing Enterobacteriaceae. All of these
organisms can be antibiotic resistant, making therapy difficult. P.
aeruginosa is the most common of these organisms causing VAP, but A. baumannii is occurring
with increasing frequency, and many hospitals have epidemics of ESBL-producing
Enterobacteriaceae and carbapenemase-producing K. pneumoniae, making the
challenges presented by these bacteria quite daunting.
P. aeruginosa is an
especially virulent organism because of its production of destructive
exoenzymes and its resistance to a wide range of antibiotics. Patients often
have upper respiratory tract (oropharynx) colonization before colonization and
infection of the lung, but primary lower respiratory tract colonization can
also occur. In the ICU, nosocomial pneumonia is the biggest concern, but this
organism can also lead to ventilator-associated tracheobronchitis, an infection
in the airway that may later progress to pneumonia. The organism is also
involved in chronic airways infections such as bronchiectasis, with or without
associated cystic fibrosis. P. aeruginosa is such a prevalent nosocomial
pathogen because it can grow in virtually any environment, and it produces a wide
range of virulence factors that allow it to infect nearly any body site. In
addition, the organism can form a biofilm on an endotracheal tube and persist
despite antibiotics and host defense mechanisms. When a critical number of
bacteria are present, they
can coordinate their growth in a biofilm and overcome host defenses through
quorum sensing, which is promoted by the release of signaling substances.
METHICILLIN-RESISTANT
STAPHYLOCOCCUS
AUREUS
This organism
has been discussed above as a cause of CAP. The strain of MRSA causing
nosocomial pneumonia is different, is more antibiotic-resistant than the
community-acquired strain, and is more prone to causing lung infection. Unlike
community-acquired MRSA, it is not a clonal disease, and bacterial virulence factors
are not as widely present. Important clinical risk factors for MRSA as a
nosocomial pneumonia pathogen are acute neurologic illness, hemodialysis, heart
disease, and solid organ transplantation. Most pneumonias are not accompanied
by bacteremia, but when they are, endocarditis should be assumed to be present,
and patients may develop metastatic infection in the brain, bones, and solid
organs, and prolonged therapy (4-6 weeks) is needed.
