Ventilator-associated pneumonia is a type of lung infection that occurs in
people who are on breathing machines in hospitals. As such, VAP typically
affects critically ill persons that are in an intensive care unit. VAP is a
major source of increased illness, and death. Persons with VAP have increased
lengths of ICU hospitalization and have up to a 20-30% death rate. The diagnosis
of VAP varies among hospitals and providers but usually requires a new
infiltrate on chest x-ray plus two or more other factors. These factors
include temperature of >38 °C or 12 × 109/ml, purulent secretions from the
airways in the lung, and/or reduction in gas exchange.
Signs and symptoms People who are on mechanical ventilation
are often sedated and are rarely able to communicate. As such, many of the
typical symptoms of pneumonia will either be absent or unable to be
obtained. The most important signs are fever or low body temperature, new
purulent sputum, and hypoxemia. Cause
= Risk factors = Risk factors for VAP include underlying
heart or lung disease, neurologic disease, and trauma, as well as
modifiable risk factors such as whether the head of the bed is flat or raised,
whether the patient had an aspiration event before intubation, and prior
antibiotic exposure. Patients who are in the ICU for head trauma or other severe
neurologic illness, as well as patients who are in the ICU for blunt or
penetrating trauma, are at especially high risk of developing VAP. Further,
patients hospitalized for blunt trauma are at a higher risk of developing VAP
compared to patients with penetrating trauma.
= Microbiology = The microbiologic flora responsible for
VAP is different from that of the more common community-acquired pneumonia. In
particular, viruses and fungi are uncommon causes in people who do not
have underlying immune deficiencies. Though any microorganism that causes CAP
can cause VAP, there are several bacteria which are particularly
important causes of VAP because of their resistance to commonly used antibiotics.
These bacteria are referred to as multidrug resistant.
Pseudomonas aeruginosa is the most common MDR Gram-negative bacterium
causing VAP. Pseudomonas has natural resistance to many antibiotics and has
been known to acquire resistance to every antibiotic except for polymyxin B.
Resistance is typically acquired through upregulation or mutation of a variety of
efflux pumps which pump antbiotics out of the cell. Resistance may also occur
through loss of an outer membrane porin channel
Klebsiella pneumoniae has natural resistance to some beta-lactam
antibiotics such as ampicillin. Resistance to cephalosporins and
aztreonam may arise through induction of a plasmid-based extended spectrum
beta-lactamase or plasmid-based ampC-type enzyme
Serratia marcescens has an ampC gene which can be induced by exposure to
antibiotics such as cephalosporins. Thus, culture sensitivities may
initially indicate appropriate treatment which fails due to bacterial response.
Enterobacter as a group also have an inducible ampC gene. Enterobacter may
also develop resistance by acquiring plasmids.
Citrobacter also has an inducible ampC gene.
Stenotrophomonas maltophilia often colonizes people who have tracheal tubes
but can also cause pneumonia. It is often resistant to a wide array of
antibiotics but is usually sensitive to co-trimoxazole
Acinetobacter are becoming more common and may be resistant to carbapenems such
as imipenem and meropenem Burkholderia cepacia is an important
organism in people with cystic fibrosis and is often resistant to multiple
antibiotics Methicillin-resistant Staphylococcus
aureus is an increasing cause of VAP. As many as fifty percent of Staphylococcus
aureus isolates in the intensive care setting are resistant to methicillin.
Resistance is conferred by the mecA gene.
Pathophysiology It is thought by many, that VAP
primarily occurs because the endotracheal or tracheostomy tube allows
free passage of bacteria into the lower segments of the lung in a person who
often has underlying lung or immune problems. Bacteria travel in small
droplets both through the endotracheal tube and around the cuff. Often,
bacteria colonize the endotracheal or tracheostomy tube and are embolized into
the lungs with each breath. Bacteria may also be brought down into the lungs with
procedures such as deep suctioning or bronchoscopy. Another possibility is
that the bacteria already exist in the mucus lining the bronchial tree, and are
just kept in check by the body's first line of defenses. Ciliary action of the
cells lining the trachea drive the mucus superiorly, leading to a build-up of
fluids around the inflated cuff where there is little to no airway clearance.
The bacteria can then colonize easily without disturbance and then rise in
numbers enough to become infective. The droplets that are driven into the
airstream and into the lung fields are lofted by way of Bernoulli's principle.
There is also a condition called oxidative damage that occurs when
concentrations of pure oxygen come into prolonged contact with cells and this
damages the cilia of the cells, thus inhibiting their action as part of the
body's first line of defense. Whether bacteria also travel from the
sinuses or the stomach into the lungs is, as of 2005, controversial. However,
spread to the lungs from the blood stream or the gut is uncommon.
Once inside the lungs, bacteria then take advantage of any deficiencies in
the immune system and multiply. A combination of bacterial damage and
consequences of the immune response lead to disruption of gas exchange with
resulting symptoms. Diagnosis
Diagnosis of ventilator-associated pneumonia is difficult and is not
standardized. The criteria used for diagnosis of VAP varies by institution,
but tends to be a combination of several of the following radiographic, clinical
sign, and laboratory evidence: Temperature greater than 38C or less
than 36C White blood cell count greater than
12,000/mm3 or less than 4,000/mm3 Purulent secretions, increased
secretions, or change in secretions Positive tracheal cultures or
bronchoalvelolar lavage cultures Some sign of respiratory distress, such
as shortness of breath, rapid breathing, abnormal breathing sounds when listening
with stethoscope Increased need for oxygen on the
ventilator Chest X-Rays: at least two serial xrays
showing sustained or worsening shadowing Positive cultures that were obtained
directly from the lung environment, such as from the trachea or bronchioles
As an example, some institutions may require one clinical symptoms such as
shortness of breath, one clinical sign such as fever, plus evidence on chest
xray and in tracheal cultures. There is no gold standard for getting
cultures or other evidence of bacterial, viral, or fungal culprit. One strategy
collects cultures from the trachea of people with symptoms of VAP. Another is
more invasive and advocates a bronchoscopy plus bronchoalveolar lavage
for people with symptoms of VAP. Both strategies also require a new or
enlarging infiltrate on chest x-ray as well as clinical signs/symptoms such as
fever and shortness of breath. Blood cultures may reveal the
microorganisms causing VAP, but are often not helpful as they are positive
in only 25% of clinical VAP cases. Even in cases with positive blood cultures,
the bacteremia may be from a source other than the lung infection.
Prevention Prevention of VAP involves limiting
exposure to resistant bacteria, discontinuing mechanical ventilation as
soon as possible, and a variety of strategies to limit infection while
intubated. Resistant bacteria are spread in much the same ways as any
communicable disease. Proper hand washing, sterile technique for invasive
procedures, and isolation of individuals with known resistant organisms are all
mandatory for effective infection control. A variety of aggressive weaning
protocols to limit the amount of time a person spends intubated have been
proposed. One important aspect is limiting the amount of sedation that a
ventilated person receives. Other recommendations for preventing VAP
include raising the head of the bed to at least 30 degrees. Antiseptic
mouthwashes such as chlorhexidine may also reduce the incidence of VAP,
although the evidence is mainly restricted to those who have undergone
cardiac surgery. American and Canadian guidelines
strongly recommend the use of supraglottic secretion drainage Special
tracheal tubes with an incorporated suction lumen as the EVAC tracheal tube
form Covidien / Mallinckrodt can be used for that reason. New cuff technology
based on polyurethane material in combination with subglottic
drainageshowed significant delay in early and late onset of VAP.
A recent clinical trial indicates that the use of silver-coated endotracheal
tubes may also reduce the incidence of VAP. There is tentative evidence that
the use of probiotics may reduced the likelihood of getting VAP, however it is
unclear if probiotics have an impact on ICU or in-hospital death.
Treatment Treatment of VAP should be matched to
known causative bacteria. However, when VAP is first suspected, the bacteria
causing infection is typically not known and broad-spectrum antibiotics are given
until the particular bacterium and its sensitivities are determined. Empiric
antibiotics should take into account both the risk factors a particular
individual has for resistant bacteria as well as the local prevalence of
resistant microorganisms. If a person has previously had episodes of
pneumonia, information may be available about prior causative bacteria. The
choice of initial therapy is therefore entirely dependent on knowledge of local
flora and will vary from hospital to hospital.
Risk factors for infection with an MDR strain include ventilation for more than
five days, recent hospitalization, residence in a nursing home, treatment
in a hemodialysis clinic, and prior antibiotic use.
Possible empirical therapy combinations include:
vancomycin/linezolid and ciprofloxacin, cefepime and gentamicintobramycin
vancomycin/linezolid and ceftazidime Ureidopenicillin plus β-lactamase
inhibitor such as piperacillin/tazobactam or
ticarcillin/clavulanate a carbapenem
Therapy is typically changed once the causative bacteria are known and
continued until symptoms resolve. For patients with VAP not caused by
nonfermenting Gram-negative bacilli the available evidence seems to support the
use of short-course antimicrobial treatments (