ARTICLE IN PRESS

Nosocomial pneumonia: State of the

science
Scott A. Flanders, MD,a Harold R. Collard, MD,b and Sanjay Saint, MD, MPHc,a
Ann Arbor, Michigan, and Denver, Colorado

Nosocomial pneumonia is the leading cause of mortality due to hospital-acquired infections. A thorough understanding of the most
recent developments in evaluating and managing nosocomial pneumonia is critical for infection control professionals and hospital
epidemiologists, given the incidence and cost of this important patient safety problem. We review the evidence on pathogenesis,
diagnosis, treatment, and prevention of both ventilator-associated and nonventilator-associated pneumonia. Key recommendations are then provided for diagnostic testing strategies, antibiotic selection, and treatment duration. We also summarize the
most recent data on how to prevent hospital-acquired infection, in general, and nosocomial pneumonia, in particular. (Am J Infect
Control 2005;n:nnn-nnn.)

Nosocomial pneumonia (NP) is the second most

common nosocomial infection after urinary tract infection but is the leading cause of mortality due to
hospital-acquired infections.1,2 Defined as pneumonia
occurring 48 hours or more after hospital admission,
NP also includes the subset of ventilator-associated
pneumonia (VAP), often defined as pneumonia developing more than 48 to 72 hours after initiation of
mechanical ventilation. Health care-associated pneumonia (HCAP), part of the continuum of NP, describes
an increasingly common proportion of pneumonia developing outside the hospital. Patients at risk for HCAP
include the following: (1) patients receiving home intravenous (IV) antibiotics, home nursing, or home wound
care; (2) residence in a nursing home or long-term care
From the University of Michigan Medical School, Department of Internal Medicine, Ann Arbor, MIa; Department of Medicine, University of
California San Francisco, San Francisco, CA and Department of Medicine, National Jewish Medical and Research Center, Denver, COb;
and Department of Veterans Affairs Health Services Research and
Development Center of Excellence, Ann Arbor, MI.c
Reprint requests: Scott A. Flanders, MD, Department of Internal Medicine, Taubman Center, 1500 E. Medical Center Drive, Room 3119F,
Ann Arbor, MI 48109-0376. E-mail: flanders@umich.edu.
Supported by a Career Development Award from the Health Services
Research and Development Program of the Department of Veterans
Affairs and a Patient Safety Developmental Center Grant from the
Agency for Healthcare Research and Quality (P20-HS11540, to S.S.).
Dr. Flanders has served as a consultant to Eli Lily, Inc., and OrthoMcNeil and has received honoraria and/or research support from
Elan and Roche.
Dr. Saint has served as a consultant to Aventis, Inc., and GlaxoSmith
Kline and has received honoraria and/or research support from the
Aetna Quality Care Research Fund and C. R. Bard, Inc.
0196-6553/$30.00
Copyright 2005 by the Association for Professionals in Infection
Control and Epidemiology, Inc.
doi:10.1016/j.ajic.2005.07.003

facility; (3) patients who have been hospitalized for $2

days in the past 90 days; and (4) patients who have received dialysis or IV therapy at a hospital-based clinic
in the past 30 days. Because these patients are at risk
for infection with antibiotic-resistant organisms, they
should be considered as having NP rather than community-acquired pneumonia.3,4 The incidence of NP depends on several factors, but published estimates
suggest rates of 5 to 10 cases per 1000 hospitalizations.5
Patients with endotracheal tubes have rates that are up
to 20-fold higher.6 The chance of infection increases
with duration of mechanical ventilation, and thus rates
presented per 1000 ventilator days more accurately reflect the risk of VAP. Overall VAP rates of 7 to 14 per 1000
ventilator days have recently been reported.7,8
The overall mortality of patients who develop NP is
quite variable but is most dependent on the setting (intensive care unit [ICU] or non-ICU) and underlying comorbid illness. The mortality attributed to an episode
of NP itself is debated but could be as high as 30%.9 Multiple studies have shown that NP increases hospital
length of stay by an average of 7 to 10 days, and, in patients with VAP, the duration of both mechanical ventilation and ICU stay is increased.10 The attributable cost for
this infection is substantial, with estimates for cost per
case of VAP ranging between $10,000 and $40,000.6,11,12
Given the importance of NP, infection control professionals (ICPs) and hospital epidemiologists should
ideally use the latest evidence in evaluating, managing,
and preventing this common patient safety problem.
Importantly, the overwhelming majority of published
work on NP involves patients in ICUs and, in particular,
focuses on VAP. Any evidenced-based overview of NP,
therefore, is largely based on experience in the ICU
population. We have previously published a primer
on the prevention of NP for the ICP13; we expand on
and update our recommendations in this state-of-thescience review.
1

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Table 1. Risk factors for nosocomial pneumonia

Impaired host defenses/increased aspiration
Endotracheal tubes
Nasogastric tubes
Enteral feeding tubes
Supine positioning
Impaired mental status
Sedation
Large inoculum of organisms
Bacterial colonization
Gastric alkalinization (enteral feeds/H2- receptor blockers)
Iatrogenic (forced hand ventilation)
Sinusitis
Malnutrition
Contaminated respiratory equipment
Overgrowth of virulent organisms
Prolonged antibiotic use
Iatrogenic (inadequate handwashing)
Central venous lines
Comorbid illness
Frequent hospitalizations
Prolonged hospital stays

PATHOGENESIS
NP results from microbial invasion of the normally
sterile lung parenchyma. Most cases of NP are due
to microaspiration of contaminated oropharyngeal or
gastric secretions.3,14 A defect in normal host defenses
(eg, endotracheal intubation), aspiration of a large innoculum of organisms, or aspiration of a particularly
virulent organism may contribute to parenchymal infection. The use of endotracheal tubes is one of the
most significant factors contributing to impaired host
defenses, and bacterial overgrowth in both gastric
and oropharyngeal secretions commonly results from
the additive effect of multiple risk factors (Table 1).

PREDICTING CAUSATIVE PATHOGENS

When a patient develops NP, the first step in management is carefully considering the likely causative
agents and, in particular, identifying whether the patient is at risk for a more virulent or resistant bacteria
that would affect antibiotic selection. Traditional thinking about bacterial etiologies of NP largely reflects the
guidelines of the American Thoracic Society, which divides patients into those who develop pneumonia early
in their hospital course (,5 days) and those who develop pneumonia later ($5 days).5 In general, the spectrum of causative organisms in patients who develop
early pneumonia reflects community isolates (Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli, nonresistant enteric gram-negative bacilli,
methicillin-sensitive Staphylococcus aureus) rather
than highly resistant nosocomial organisms. Patients
who develop late-onset NP, on the other hand, are
more likely to have resistant organisms (Pseudomonas

Flanders, Collard, and Saint

aeruginosa, Acinetobacter species, other resistant enterobacter species, methicillin-resistant Staphylococcus

aureus [MRSA]). Importantly, many cases of NP, especially VAP, are polymicrobial.9,15
Additional clinical variables, however, appear more
important than time of onset in predicting the causative
organism in NP. A prospective study of over 3600 patients admitted to an ICU compared patients with early
(,5 days after ICU admission) versus late onset (5 or
more days after ICU admission) NP.16 Of patients with
early onset NP, Pseudomonas, MRSA, and Acinetobacter
were isolated in 25%, 18%, and 6% of patients, respectively. In this sample, 78% of patients with early onset
disease had received prior broad-spectrum antibiotics,
and 49% had been in the hospital at least 24 hours prior
to admission to the ICU. These data support the argument that prior antibiotics and prior hospitalization
may be more important than timing of onset when considering causative organisms. Other investigators have
found that, in the absence of prior antibiotic therapy
or a prolonged hospital stay, the risk of harboring a
highly resistant organism is much lower.17,18
Clinical risk factors and comorbidities can also help
identify likely causative pathogens. Patients with coma,
head trauma, diabetes mellitus, and renal failure are
predisposed to infection with S aureus5; patients with
prolonged ICU stays, prior antibiotics, corticosteroid
use, and structural lung disease are at risk for infection
with Pseudomonas. Legionella infection in NP is usually seen in immunocompromised patients or in local
hospital outbreaks because of contaminated water supplies. Anaerobic organisms are not commonly implicated in NP.19,20
Because most of the epidemiologic data regarding NP come from ICUswith a majority of patients receiving mechanical ventilationunfortunately, little is
known about causative organisms in patients who develop NP outside of the ICU. Data from some institutions that include hospital-wide surveillance suggest
that the bacteriology of NP in nonventilated patients
is similar to that in ventilated patients.3 That may not
be the case when ICU patients are excluded. A recent study of NP in non-ICU patients found that Streptococcus pneumoniae and Legionella pneumophilia were
the most commonly isolated organisms; however,
methodologic problems with this study limit its generalizability.21 Additionally, the incidence of resistant
organisms varies widely between institutions and
even on different wards within an institution. This underscores the importance of collecting and tracking
institutional epidemiologic data regarding NP. The ICP
can improve provider knowledge by feeding back this
institutional data on potential causative organisms
and hopefully improving the appropriateness of initial
empiric therapy for patients with NP.

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Flanders, Collard, and Saint

Diagnostic approach
The diagnosis of NP remains controversial. A variety
of diagnostic modalities exist and have been evaluated,
yet the diagnostic testing literature is plagued by methodologic limitations,22 often because of lack of a clear
gold standard. NP can either be diagnosed solely on
clinical grounds or via microbiologic testing (often invasively obtained) in a setting of clinically suspected
NP. A clinical diagnosis generally requires a new, persistent infiltrate on chest radiograph (CXR) not because of
another process, along with signs consistent with infection such as fever, purulent sputum, and leukocytosis. Clinical diagnosis of NP is sensitive (ie, it is unlikely
to miss cases of NP) but not specific and can lead to antibiotic overuse. Invasive diagnostic strategies for NP
generally use bronchoscopy to obtain quantitative cultures using a protected specimen brush (PSB) device to
limit contamination or bronchoalveolar lavage (BAL). A
patient is considered to have nosocomial pneumonia
when culture results reveal more than 103 organisms/
mL if bronchoscopy with PSB is performed or more
than 104 organisms/mL with standard BAL. Invasive diagnosis is more specific but can lead to false-negative
results, especially if antibiotics have been recently
changed.9,23
A clinical diagnosis of NP likely leads to antibiotic
overuse, yet pursuing a bronchoscopic diagnosis is invasive, costly, and requires technical expertise. Identifying a diagnostic approach between these extremes is
therefore important. Some have attempted to improve
on clinical diagnosis by making it more quantitative.
Pugin et al evaluated patients with suspected VAP
and assigned points for clinical variables (temperature,
white blood cell count, tracheal secretions, oxygenation,
CXR abnormalities, and semiquantitative endotracheal
aspirates) depending on their degree of abnormality
and then assigned an overall score (the clinical pulmonary infection score) for each patient. The score correlated well with quantitative BAL, and scores .6 strongly
suggested infection.24 A recent analysis, however,
showed that, when compared with a diagnostic strategy
of bronchoscopically obtained quantitative cultures,
using the clinical pulmonary infection score still led
to potentially unnecessary treatment in a substantial
number of patients.25 Endotracheal aspirates (ETA),
with or without quantitative cultures, have been shown
to be highly sensitive (90%-100%) when compared
with anything other than a clinical diagnosis as the
gold standard.26 When compared with bronchoscopy,
endotracheal aspirates usually identify all organisms
subsequently found on BAL or PSB.26 The specificity,
however, is much lower, and false positives are likely.
Attempts to further improve the specificity without
losing sensitivity have focused on nonbronchoscopic

n 2005

sampling of the distal airways. This can be achieved

by blind mini-BAL or blind PSB (using a blind telescoping catheter) in which a catheter is blindly inserted
through an endotracheal tube to sample distal airways.
When compared with postmortem lung histology and
culture, mini-BAL has appeared to provide both a sensitivity and specificity above 80%,9,27 whereas blind
PSB has performed similarly with a high concordance
rate when compared with bronchoscopic PSB.9,28,29
Thus, nonbronchoscopically obtained quantitative
cultures appear to improve on specificity without
much compromise in sensitivity. Their use, however,
is limited to mechanically ventilated patients.
Few trials have prospectively compared clinical outcomes for NP patients undergoing different diagnostic
strategies. The most notable was a multicenter trial of
413 patients with suspected VAP. Patients were randomized in an unblinded fashion to a diagnostic strategy of
noninvasive endotracheal aspirates with qualitative
cultures or an invasive diagnostic strategy that included
either BAL or PSB with quantitative cultures. Patients
managed with the invasive strategy had fewer positive
cultures, which translated into more antibiotic-free
days and reduced mortality at 14 days (16% vs 26%, respectively, P 5 .02), possibly because of a more aggressive search for VAP mimickers in invasively diagnosed
patients.30 Other studies, however, have found no
difference in outcomes when comparing diagnostic
strategies for NP,31,32 and, as a result, no firm recommendation favoring an invasive diagnostic approach
can be made.
Multiple studies of biologic markers of infection
have attempted to find a noninvasive, rapid, and accurate means of determining who needs antibiotics for
presumed NP. Unfortunately, the results have largely
been disappointing. More recently, measurement of a
soluble triggering receptor expressed on myeloid cells
(sTREM-1) that is up-regulated in the setting of infection has been shown to have potential to improve our
ability to accurately diagnose pneumonia. When compared with post hoc physician consensus, measurement of sTREM-1 by mini-BAL was shown to be 98%
sensitive and 90% specific for the diagnosis of pneumonia in mechanically ventilated patients.33 Although
promising, additional studies are required prior to this
test being widely recommended as part of a routine
diagnostic algorithm.
The most recent joint American Thoracic Society
(ATS)/Infectious Diseases Society of America (IDSA)
guidelines recommend obtaining samples of lower respiratory tract secretions before any antibiotic changes
in all patients with suspected NP. The guidelines
list ETA, BAL, and PSB as potential sampling techniques, highlighting the strengths and weaknesses of
each.3

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In summary, there are no convincing data that

support 1 diagnostic strategy over another. In their
absence, we make the following comments and
recommendations:
1. A clinical diagnosis (new infiltrate, fever, purulent
sputum, leukocytosis) is valuable in screening for
patients with suspected NP.
2. Arguably, a diagnostic test should be performed on
patients suspected of having NP to evaluate for a
causative organism.
3. In non-ICU, nonventilated patients, although untested, we believe an attempt should be made to
obtain a sputum sample to help guide antibiotic
therapy.
4. In the critically ill, mechanically ventilated patient,
we suggest the use of quantitative cultures, which
may help prevent antibiotic overuse without adversely affecting outcomes. An endotracheal aspirate
with quantitative cultures should be obtained at a
minimum.
5. An invasive workup with bronchoscopically obtained cultures may be the preferred strategy for patients with suspected late-onset VAP (after 5-7 days
on the ventilator), patients who are failing empiric
antibiotic therapy, patients who are at risk for an unusual pathogen (eg, immunocompromised patients),
or patients suspected of having an alternative
diagnosis.
6. When ICPs are comparing rates of NP among institutions, or benchmarking, the diagnostic approach (ie,
what criteria are required to qualify as a case of NP)
needs to be standardized. One common algorithm
used in over 300 US hospitals is the Centers for Disease Control and Preventions (CDC) National Nosocomial Infection Surveilance (NNIS) pneumonia flow
diagram.34 The algorithm incorporates both clinical
and microbiologic data and has been instrumental
in allowing for intrahospital and interhospital
comparisons.34,35

Antibiotic treatment strategies

Several studies strongly suggest that patients treated
with adequate initial empiric antibiotic therapy (ie, the
antibiotics administered are shown to be active against
all organisms isolated) have lower mortality rates than
patients treated with inadequate initial antibiotic therapy.36-38 In many of these studies, inappropriate initial
empiric therapy was one of the strongest independent
predictors of mortality.39,40 The need to choose appropriate antibiotics correctly and expeditiously drives the
use of broad-spectrum antibiotics. This creates a dilemma when balanced against efforts to reduce the
use of inappropriate broad-spectrum antibiotics, which

Flanders, Collard, and Saint

attempt to prevent the development of highly resistant

organisms.41
Treatment strategies need to balance the need for
appropriate initial empiric therapy with avoidance of
unnecessary antibiotic overuse. Obviously, if there
were a better diagnostic test for NP, we could target
therapy at only those patients with a true bacterial
infection. In the absence of such a test, two strategies
remain: (1) Identify patients at low risk for resistant organisms who can avoid broad-spectrum antibiotics,
and (2), in patients at high risk for infection with resistant organisms, start broad-spectrum antibiotics but
deescalate therapy as rapidly as possible.
Low-risk patients. Identifying patients who are at
low risk for resistant organisms based on clinical
factors is an important first step. This allows for more
narrow, but reliably effective, antibiotic therapy. Such
low-risk patients include those who are not critically
ill, have not had multiple hospitalizations, have not received prior broad-spectrum antibiotics, and develop
their infection within 4 to 5 days of hospitalization.
In these patients, antibiotics should target common
community-acquired organisms in addition to S aureus
and the Enterobacter species. Appropriate initial selections would be a b-lactam/b-lactamase inhibitor or
a nonpseudomonal third generation cephalosporin.5
Unfortunately, todays hospitalized population is becoming increasingly complex and, especially in ICUs,
low-risk patients are uncommon.
High-risk patients. Patients who do not meet the
above low-risk criteria are considered to be at high
risk for potentially resistant organisms and need empiric antibiotic coverage active against gram-negative
organisms such as P aeruginosa and even Acinetobacter.3,17 This requires the use of drugs such as imipenem
(perhaps with an aminoglycoside) or a combination of
a b-lactam/b-lactamase inhibitor, with a fluoroquinolone, and vancomycin (to cover against MRSA). In these
cases, the approach to limiting antibiotic overuse is
de-escalation therapy. This treatment principle acknowledges that broad therapy is warranted in many
patients initially but that treatment may be narrowed
considerably as culture results identify the causative
organism and its sensitivities. Deescalation therapy
focuses on limiting the duration of therapy and narrowing therapy as soon as possible.42
Is rapidly narrowing therapy and using shorter
courses of treatment safe? Until recently, little data described how long an episode of NP or VAP should be
treated. As a result, patients often receive broad-spectrum agents for 14 to 21 days. Clinical resolution after
an episode of NP requires a mean of 6 days, and, importantly, colonization with resistant organisms does not
appear to develop until after 7 days of therapy.43 This
suggests that a shorter duration of antibiotic treatment

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may actually be preferred. A 7-day treatment duration

goal was incorporated into a NP treatment guideline
for nonneutropenic, nonbacteremic patients at a large
tertiary care medical center.44 The guideline recommended broad initial empiric therapy but also suggested early treatment modification based on culture
results. Patients treated after the guideline was implemented had shorter antibiotic courses and, as a result,
were less likely to develop a secondary NP episode.
There was no effect on mortality or ICU length of stay.
Another attempt at evaluating deescalation techniques
was made by researchers at a Veterans Affairs medical
center trying to reduce antibiotic use by targeting short
course therapy at low-risk patients as determined by
the clinical pulmonary infection score.45 Patients
with higher risk features and clinical pulmonary infection scores of greater than 6 were treated for a full 10 to
21 days. Patients with scores of 6 or less were randomized to either standard 10- to 21-day therapy or 3-day
therapy, at which time the score was reassessed, and,
if still #6, antibiotics were stopped at day 3. If the score
had increased, the patients were treated for 10 to 21
days. Patients randomized to 3-day therapy had less antibiotic use, lower antibiotic costs, and shorter ICU
stays. There was also a trend toward lower mortality
at 14 and 30 days (P 5 .06). Patients treated with a
shorter course were also statistically significantly less
likely to develop superinfection (subsequent isolation
of a new organism) or infection with a resistant
organism.
A recent trial conducted in 51 ICUs in France randomized over 400 patients with VAP to either 8 days
or 15 days of antibiotics. When compared with 15day treatment, patients treated for 8 days had no excess
mortality or recurrent infections but did have more antibiotic-free days, and, when recurrent infections did
develop, the patients treated for 8 days were less likely
to have a multiresistant pathogen. A subset of patients
in the 8-day treatment group infected with nonfermenting gram-negative bacilli (eg, Pseudomonas
aeruginosa) did have a higher pulmonary infection
recurrence rate (40.6% vs 25.4%, respectively; difference, 15.2%; 90% CI: 3.9%-26.6%), but, because of
aggressive surveillance for recurrent infection, this
did not translate into a higher mortality risk in this
subset of patients.46
In an effort to apply aggressive antibiotic discontinuation techniques in a real-world setting, Micek et al
randomized patients with suspected VAP to an antibiotic treatment duration based on treating physician
opinion or a formal rapid discontinuation policy. The
physicians of patients randomized to the discontinuation policy received a recommendation for stopping
all antibiotics if a noninfectious etiology for pulmonary infiltrates was found or if signs and symptoms

n 2005

suggesting active infection had resolved. The patients

in the intervention arm achieved a shorter antibiotic
treatment duration (6.0 days vs 8.0 days, respectively,
P 5 .0001) without any affect on clinical outcomes,
supporting the safety of attempts at deescalating
therapy.8
In summary, a rational strategy for the treatment of
patients with suspected NP first starts with immediate
initiation of antibiotics and collection of respiratory secretions. Identification of low-risk patients provides a
subset that can receive narrower spectrum empiric
therapy. In higher risk or clinically unstable patients,
initial empiric therapy should be broad but quickly narrowed based on microbiologic culture results. The ICP
can play a vital role by feeding back culture and sensitivity data to care providers, thereby facilitating appropriate antibiotic utilization. The data demonstrate that
reducing overall treatment duration (1 week) is safe, effective, and less likely to promote the growth of resistant
organisms in patients who are clinically improving.
Patients infected with nonfermenting, gram-negative
bacilli, however, may need a longer duration of treatment (2 weeks).

PREVENTION
The clinical and financial consequences of NP justify
aggressively pursuing strategies aimed at preventing its
development. Preventive strategies are either directed
at reducing the overall incidence of infectious complications in hospitalized patients or they are specifically
targeted at reducing the incidence of NP. In the case
of the latter, preventive measures address the modifiable risk factors highlighted in Table 1. As is the case
with most issues related to NP, a majority of the literature supporting preventive strategies is limited to patients in the ICU and, in particular, patients receiving
mechanical ventilation. Recent reviews have addressed
in detail both effective and more controversial preventive strategies for both VAP47,48 and NP.1 As a result, we
chose to focus on the highest yield preventive strategies
that can be readily implemented by the ICP.

General preventive strategies

Most general preventive strategies are aimed at
avoiding contamination of patients with antimicrobialresistant organisms that exist in hospitals or mitigating
the emergence of antimicrobial-resistant organisms in
the first place.
Preventing iatrogenic spread. Careful handwashing
both before and after patient contact has been shown
to reduce the incidence of nosocomial infection49-52
but is unfortunately often overlooked in the fast-paced
hospital environment. Clusters of NP cases attributed to
poor hand hygiene have been described, and careful

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handwashing remains an important defense against

nosocomial infection spread. Plain soap and water
may actually be inferior to antibacterial soaps (chlorhexidine based) and alcohol-based hand rinses.51 In
addition, the use of alcohol-based handwash in bedside
dispensers likely improves compliance with hand
hygiene recommendations. Because use of artificial
fingernails among health care providers has recently
become known as a significant risk factor for colonization and subsequent spread of resistant organisms,
guidelines recommend against their use by personnel
with direct patient contact, especially in ICU and surgical settings.51
Reducing emergence of resistant organisms. Indwelling devices such as central lines and urinary catheters increase the risk of colonization with resistant
organisms and should be used only when absolutely
necessary.53 When these devices are needed, efforts
should focus on their timely removal.54 The use of sterile barrier precautions (mask, cap, gown, gloves, and
large sterile drapes) during insertion of central venous
lines can reduce infectious complications, including
colonization and subsequent bloodstream infections.55
The control of antibiotic use has been central to
many preventive strategies. Prolonged use or unnecessary use of broad-spectrum antibiotics is strongly associated with development and colonization of resistant
organisms. A complete discussion of antibiotic control
measures is beyond the scope of this overview, but, as
discussed earlier, efforts focused at reducing use of
broad-spectrum regimens and shortening treatment
durations have reduced rates of colonization and recurrent episodes of NP. More recently, several investigators
have combined antibiotic restriction with antibiotic
rotation as a measure to control resistant organisms.
Many studies have shown that these antibiotic rotation
schemes and class switches lead to decreases in rates
of VAP and a reduced prevalence of resistant organisms.56,57 The complexity of the rotation schedules,
uncertainty over the sustainability of results,58 methodologic limitations of the studies, and potential to
increase resistance to newly introduced antibiotics if
done without other preventive strategies, however,
have all prevented widespread adoption of this practice.

Targeted preventive strategies

Preventive strategies to lower the incidence of NP focus on reducing or eliminating risk factors (Table 1) for
oropharyngeal or gastric colonization and subsequent
aspiration of contaminated oropharyngeal or gastric
secretions.
Noninvasive ventilation. Endotracheal intubation is
one of the most important risk factors contributing to
pneumonia in patients requiring mechanical support

Flanders, Collard, and Saint

for respiratory failure. Increasingly, the use of noninvasive ventilation (NIV) or positive-pressure mask ventilation in selected groups of patients has been effective in
preventing endotracheal intubation. In a randomized
controlled trial of patients admitted with an acute exacerbation of chronic obstructive pulmonary disease
(COPD), standard medical care combined with NIV
was associated with significant reductions in endotracheal intubation, hospital length of stay (LOS), complications (including NP), and mortality when compared
with standard medical care alone.59 A subsequent
case-control study of well-matched patients with acute
exacerbations of COPD or cardiogenic pulmonary
edema (CHF) compared clinical outcomes between
NIV and mechanical ventilation. The use of NIV was associated with lower rates of all nosocomial infections
as well as NP (18% vs 60%, P , .001, and 8% vs 22%,
P 5 .04, respectively). Patients treated with NIV also
had shorter ICU LOS, lower mortality, and received
less antibiotics.60 Although not appropriate for all patients (such as those with facial trauma or altered mental status), the use of NIV in selected populations with
acute COPD61,62 and CHF exacerbations appears safe
and may reduce the likelihood of NP.63 Of note, a recent
trial evaluating the use of NIV for respiratory failure
developing after planned extubation showed no benefit in avoiding reintubation and was associated with
increased mortality.64
Semirecumbent patient positioning. Supine positioning may contribute to the development of VAP,
likely because of an increased risk of gastric reflux
and subsequent aspiration. Three studies have evaluated the efficacy of semirecumbent positioning (elevation of the head of the bed .45 degrees). Two small
evaluations used surrogate outcomes of reflux and aspiration events, both of which were reduced with semirecumbent positioning.65,66 A subsequent randomized
controlled trial in 86 mechanically ventilated patients
was stopped early after semirecumbent positioning
was associated with a significant reduction in VAP
(OR, 0.16; 95% CI: 0.03-0.67).67 Unfortunately, scant
data exist on patient positioning outside the ICU in
nonventilated patients.
Subglottic secretion drainage. The pooling of contaminated secretions above the cuff of the endotracheal tube may predispose patients to aspiration and
subsequently VAP. Removal of these secretions could
theoretically reduce the risk of developing pneumonia.
Subglottic secretion drainage requires specially designed endotracheal tubes with a separate lumen that
opens into the subglottic region above the tracheal
cuff. A recent metaanalysis of the 5 studies that have
evaluated this preventive strategy found that subglottic
secretion drainage significantly reduces the incidence
of VAP and should be considered for use in patients

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requiring more than 3 days of mechanical ventilation.68 Although these endotracheal tubes are more expensive, at least 1 cost-effectiveness analysis showed
cost savings of $1900 per episode of VAP prevented.69
Stress ulcer prophylaxis. Medications that increase
gastric pHsuch as H2-antagonists and antacidsallow
for colonization of the upper gastrointestinal tract by
potentially pathogenic organisms and therefore may
increase the risk for NP. Sucralfate, an agent often
used for stress ulcer prophylaxis, has limited effect
on gastric pH and thus may not increase the risk for
pneumonia. Seven metaanalyses of over 20 randomized trials have evaluated the risk of NP in critically ill
patients associated with the use of stress ulcer prophylaxis48: Four showed significant reductions in the
incidence of pneumonia, and 3 showed similar but
nonsignificant trends toward reduced pneumonia in
patients treated with sucralfate. Three analyses found
a mortality benefit with the use of sucralfate when
compared with H2-antagonists. A recent large randomized trial, however, compared sucralfate with H2-antagonists and found no effect on pneumonia but a
significant increase in the risk of clinically important
bleeding with the use of sucralfate.70 Health care practitioners must weigh the potential benefit in reduction
of pneumonia with the use of sucralfate against the
increased risk of gastrointestinal bleeding when compared with H2-antagonists. Of note, a recent trial of
287 patients in a surgical ICU assessed the risk of
both pneumonia and stress-related bleeding in patients
randomized to omeprazole, famotidine, sucralfate, or
placebo and found no statistically significant differences in bleeding or pneumonia rates between the 4
study groups.71
The data currently do not support a mortality benefit
in most patients who receive stress ulcer prophylaxis.72 Furthermore, the available evidence does not
conclusively demonstrate that the benefits of gastrointestinal prophylaxis outweigh its risks for every patient
in the ICU.72 Because some of the agents used as stress
ulcer prophylaxis may increase the risk of NP, identifying patients at high risk of stress gastritis who are most
likely to benefit from stress ulcer prophylaxis is imperative. Well-designed studies suggest that this population is limited to patients with shock, respiratory
failure, and coagulopathy.73 Using these criteria, most
patients who are not in the ICU should not receive
stress ulcer prophylaxis.
Oral hygiene. Given the potential role of colonizing
oropharyngeal bacteria in the development of NP, it
would seem that improving oral hygiene could prevent
many cases of NP. Improvement in oral hygiene in elderly nursing home residentsby the use of antiseptic
mouthwash, brushing teeth after all meals, and weekly
plaque removalhas been linked to reduced rates of

n 2005

aspiration pneumonia.74,75 However, to our knowledge, no prospective study of routine dental care in
hospitalized patients has shown reduced rates of NP.
The use of chlorhexidine 0.12% oral rinse has been associated with reduced rates of VAP in both cardiac surgery patients and surgical ICU patients and thus should
be considered for use in those populations.76,77
Selective digestive decontamination. Selective digestive decontamination (SDD) involves sterilization
of the oropharynx and gastrointestinal tract in mechanically ventilated patients to prevent aspiration of
large numbers of potentially pathogenic organisms
and subsequent VAP. Most evaluations of SDD have involved the oral (and at times gastric) application of topical polymixin, aminoglycoside, and amphotericin. In
many cases, investigators have added short courses of
intravenous antibiotic therapy. There have been 10
metaanalyses of over 40 randomized trials of SDD
that have been recently summarized in systematic
reviews.47,48 The preponderance of evidence suggests
that there is a significant reduction in the risk of VAP
with the use of SDD. Several metaanalyses also suggest
that, in addition to reductions in VAP, the combination
of topical and IV antibiotics may provide a mortality
benefit.48 A recent review of 32 trials of SDD, however,
found an inverse relationship between reported benefit
and methodologic quality.78 In this context, the results
of metaanalyses may overstate the benefit.
In addition, it is unclear how routine use of SDD
might affect antibiotic resistance patterns. This is currently a topic of much debate. At least 1 recent study
has suggested that the incidence of resistant organisms
is not significantly increased in patients receiving
SDD.79 This study did not address the emergence of
MRSA, a previously reported consequence of SDD.80,81
Although a second recent study suggested effective
control of MRSA with the addition of topical vancomycin to the SDD regimen,82 there is still no consensus on
the effect of SDD on the emergence of resistant organisms. Therefore, although SDD is likely an effective
preventive measure, continued evaluation of delayed
complications related to antibiotic resistance is warranted before SDD is widely implemented.
Ventilator circuit management strategies. There
has been substantial interest in the potential role of
contaminated or colonized tubing, filters, and other
components of the ventilator circuit in the pathogenesis of VAP. Most ventilator management issues are beyond the scope of practice of most ICPs and have
been recently reviewed in detail elsewhere.47,48

The role of the ICP in prevention

Although many of the individual tools for preventing
NP available to the ICP have been described in detail

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8

Flanders, Collard, and Saint

Vol. n No. n

above, the most important tool that an ICP has is serving as the local champion of evidence-based practices,
thereby taking ownership of NP-related preventive processes. Most institutions that have succeeded in reducing rates of NP have done so by carefully tracking rates
of NP, creating multidisciplinary teams to develop targeted preventive strategies, and bundling multiple
preventive strategies into a single project. The ICP is
perfectly positioned to help drive this process. An educational intervention developed by a multidisciplinary
team at an urban teaching hospital and targeted at
nursing and respiratory therapists was successful at reducing the rate of VAP by nearly 58%.83 Most recently,
the Institute for Healthcare Improvements (IHI) 100,000
Lives Campaign that focuses on improving health care
safety has targeted prevention of VAP. The IHI recommends bundling multiple preventive strategies into
1 package that can be implemented all at once, rather
than targeting 1 preventive strategy at a time. Resar
et al recently found that bundling led to a 44% reduction in VAP rates in 35 ICUs across the United
States.84 ICP involvement is crucial to the success of
coordinated activities aimed at preventing VAP and
other hospital-acquired infections.

CONCLUSION
NP is a common and costly complication of hospitalization. Although much is known about the epidemiology, pathogenesis, diagnosis, and treatment of this
important patient safety problem, additional studies
are necessary. We believe the approach to management
should include an attempt to identify patients who are
at low risk for resistant organisms. These patients can
be treated with narrower spectrum antibiotics. Highrisk patients, however, will need initial empiric therapy
with broad-spectrum antibiotics. Diagnostic testing
should be performed in all patients. We favor the use
of quantitative cultures of respiratory secretions obtained noninvasively, or invasively in selected patients,
and prior to starting or changing antibiotic therapy.
Once antibiotics are begun, every attempt should be
made to tailor therapy to culture results and shorten
duration of treatment to 7 or 8 days. After carefully
considering the potential benefits and risks involved,
we recommend the following methods for preventing
NP: semirecumbent positioning in all ventilated patients unless contraindicated, avoidance of unnecessary use of H2 blockers and perhaps proton pump
inhibitors for stress gastritis prophylaxis, and subglottic secretion drainage in patients expected to receive
mechanical ventilation for greater than 3 days.
Future economic evaluations should be undertaken
to confirm the cost effectiveness of methods to prevent
NP because decision makers increasingly rely on these

types of analyses prior to implementing infection

control interventions.85 Additionally, although data on
mechanically ventilated patients are available, there
are few data derived from nonventilated, noncritically
ill patients on the general hospital ward. Such studies
are required to confirm the efficacy of the above strategies in this population. Perhaps ICPs may wish to
work collaboratively with hospitalistsan emerging
physician group who are increasingly caring for hospitalized patientsto conduct such studies.86,87 Finally,
although some investigations have focused on translating proven preventive methods into practice,88 additional work is required to understand better how to
best implement evidence-based recommendations.
The authors thank Lisa Sturm, MPH, CIC, Infection Control and Epidemiology, University of Michigan Hospitals and Health Centers, for her thoughtful comments on an earlier draft of this manuscript.

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