Recognition and prevention of nosocomial pneumonia in the
intensive care unit and infection control in mechanical ventilation
Lee E. Morrow, MD, MSc; Marin H. Kollef, MD
P
neumonia associated with the
need for mechanical
ventila-tion in the intensive care unit
(ICU) setting is one of the most
common infections managed by
intensiv-ists. The current classification of
pneu-monia in the ICU includes
community-acquired pneumonia, hospital-community-acquired
pneumonia (HAP), ventilator-associated
pneumonia (VAP), and nursing
home-associated pneumonia (Table 1) (1–3).
Health care-associated pneumonia
(HCAP) is the newest category of
pneu-monia, and in many developed countries,
it is probably the most common type of
pneumonia requiring ICU care. HCAP is a
distinct type of nosocomial pneumonia
(NP), the others being HAP and VAP, that
is present at the time of hospital or ICU
admission where patients have specific
underlying risk factors, including
resi-dence in a nursing home or long-term
care facility, recent hospitalization or
treatment with antibiotics, receipt of
home or hospital-based intravenous
ther-apy, wound care, dialysis, and significant
immunosuppression (2, 3).
HCAP patients are more similar to
pa-tients with HAP and VAP and differ from
patients with community-acquired
pneu-monia because of the common presence
of infection with multidrug-resistant
bac-teria and the greater presence of
comor-bidities, including cancer, chronic kidney
disease, heart disease, chronic
obstruc-tive lung disease, immunosuppression,
dementia, and impaired mobility (4 – 8).
From a prevention standpoint, HAP and
VAP are most amenable to prevention
strategies applied in the hospital setting.
However, the prevention of pneumonias
developing outside of the hospital
(com-munity-acquired pneumonia, HCAP) can
also be accomplished, to some extent,
through the use of specific hospital-based
strategies as outlined in this manuscript
(9, 10). The medical literature and
avail-able clinical evidence are currently most
robust for VAP and less developed for
HAP and HCAP. Therefore, we will focus
on VAP as the paradigm for our
discus-sion of NP, and the reader should assume
that our comments also apply to HAP and
HCAP unless otherwise stated.
Diagnosis of NP
Clinical and Radiographic Diagnosis.
Clinical criteria are nonspecific for the
diagnosis of NP. Clinical findings, such as
fever, leukocytosis, and purulent
secre-tions, are known to complicate other
noninfectious pulmonary conditions,
such as atelectasis and the acute
respira-tory distress syndrome and therefore lack
specificity for the diagnosis of NP (11,
12). Similarly, the chest radiograph can
be nonspecific for the diagnosis of NP.
Wunderink et al (13) showed that no
roentgenographic sign correlated well
with the presence of pneumonia in
me-chanically ventilated patients. By
step-wise logistic regression, the presence of
air bronchograms was the only
roentgen-ographic sign that correlated with
autop-sy-verified pneumonia, correctly
predict-ing 64% of cases. The most frequently
employed clinical diagnosis of VAP has
traditionally required the presence of a
new or progressive consolidation on
chest radiology plus at least two of the
following clinical criteria: fever
⬎
38°C,
leukocytosis or leukopenia, and purulent
secretions. This definition has been
sup-ported by several medical specialty
From the Department of Medicine (LEM), Creighton University Medical Center, Omaha, NE; and the Division of Pulmonary and Critical Care Medicine (MHK), Wash-ington University School of Medicine, St. Louis, MO.
Dr. Kollef’s work was supported, in part, by the Barnes-Jewish Hospital Foundation. Dr. Morrow has received honoraria from C. R. Bard and funding from the National Institutes of Health. Dr. Kollef has held consultancies for Pfizer, Merck, Kimberly-Clark, Astel-las, and Bard Medical, and received honoraria from Pfizer, Merck, Johnson & Johnson, and AstraZeneca. For information regarding this article, E-mail: [email protected]
Copyright © 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins
DOI: 10.1097/CCM.0b013e3181e6cc98
Nosocomial pneumonia (NP) is a difficult diagnosis to establish
in the critically ill patient due to the presence of underlying
cardiopulmonary disorders (e.g., pulmonary contusion, acute
re-spiratory distress syndrome, atelectasis) and the nonspecific
ra-diographic and clinical signs associated with this infection.
Ad-ditionally, the classification of NP in the intensive care unit setting
has become increasingly complex, as the types of patients who
develop NP become more diverse. The occurrence of NP is
espe-cially problematic as it is associated with a greater risk of
hospital mortality, longer lengths of stay on mechanical
ventila-tion and in the intensive care unit, a greater need for
tracheos-tomy, and significantly increased medical care costs. The adverse
effects of NP on healthcare outcomes has increased pressure on
clinicians and healthcare systems to prevent this infection, as
well as other nosocomial infections that complicate the hospital
course of patients with respiratory failure. This manuscript will
provide a brief overview of the current approaches for the
diag-nosis of NP and focus on strategies for prevention. Finally, we will
provide some guidance on how standardized or protocolized care
of mechanically ventilated patients can reduce the occurrence of
and morbidity associated with complications like NP. (Crit Care
Med 2010; 38[Suppl.]:S352–S362)
groups (14, 15), despite the lack of
spec-ificity for these criteria (11–13).
More recently, attempts have been
made to develop prediction models or
scoring systems for NP. The Centers of
Disease Control and Prevention/National
Healthcare Safety Network has
estab-lished a clinical definition for the
pres-ence of probable NP (Table 2) (16).
Un-fortunately, these diagnostic criteria have
not been validated clinically and at least
one study (17) found that decision
mak-ing usmak-ing these criteria was less accurate,
potentially resulting in the withholding
of antibiotics in 16% of patients
diag-nosed with VAP by bronchoalveolar
la-vage (BAL). The Clinical Pulmonary
Infec-tion Score (CPIS) is another diagnostic tool
for establishing the presence of NP based
on six variables (fever; leukocytosis;
tra-cheal aspirates; oxygenation; radiographic
infiltrates; and semiquantitative cultures of
tracheal aspirates with Gram-negative
stain) (Table 3) (18). The original
descrip-tion showed a sensitivity of 93% and
spec-ificity of 100%, but this study included only
28 patients and the CPIS was compared
with quantitative culture of BAL fluid,
us-ing a “bacterial index” defined as the sum of
the logarithm of all bacterial species
recov-ered, which is not considered an acceptable
standard for the diagnosis of VAP.
Com-pared to pathologic diagnosis, CPIS has
demonstrated a moderate performance
with a sensitivity between 72% and 77%
and specificity between 42% and 85% (11,
19). Similarly, CPIS has not been found to
be accurate compared to quantitative
bac-terial cultures of the lower respiratory tract
for the diagnosis of VAP with a sensitivity
between 30% and 89% and specificity
be-tween 17% and 80% (19 –24).
Microbiological/Etiological Diagnosis.
Several studies have evaluated the value
of quantitative bacteriologic data in
es-tablishing the diagnosis of VAP compared
to pathologic and clinical criteria. Torres
et al (25) used quantitative cultures of
respiratory specimens obtained by BAL
(bacterial count threshold
⫽
10
4colony-forming units [cfu]/mL), protected BAL
(10
4cfu/mL), protected specimen brush
(10
3cfu/mL), and tracheobronchial
aspi-rate (10
5cfu/mL) that were compared
with histology of lung biopsy samples to
establish the diagnosis of VAP.
Sensitivi-ties for the diagnosis of VAP ranged from
16% to 37% when only histologic
refer-ence tests were used, whereas specificity
ranged from 50% to 77%. When lung
histology of guided or blind specimens
and microbiology of lung tissue were
combined, all quantitative diagnostic
techniques achieved relatively higher,
but still limited, diagnostic yields
(sensi-Table 1. Pneumonia classification for patients in the intensive care settingCAP ●Infection present at hospital admission in patients who do not meet the criteria for HCAP
HCAP ●Pneumonia present at hospital or ICU admission in patients with at least one of the following risk factors:
●Hospitalization forⱖ2 days in an acute care facility within 180 days of infection ●Residence in a nursing home or long-term care facility
●Antibiotic therapy, chemotherapy, or wound care within 30 days of current infection
●Hemodialysis treatment at a hospital or clinic ●Home infusion therapy or home wound care ●Family member with infection due to MDR bacteria
●Significant immune suppression (corticosteroids, HIV, organ transplant) NHAP ●Pneumonia occurring during residence in a nursing home or rehabilitation facility HAP ●Pneumonia occurring typicallyⱖ48 hrs after hospital admission in a nonintubated
patient
VAP ●Pneumonia occurring typically⬎48 hrs after hospital admission and endotracheal intubation
CAP, community-acquired pneumonia; HCAP, healthcare-associated pneumonia; ICU, intensive care unit; HIV, human immunodeficiency virus; MDR, multidrug resistant; NHAP, nursing home-associated pneumonia; HAP, hospital-acquired pneumonia; VAP, ventilator-home-associated pneumonia.
Table 2. Centers of Disease Control and Prevention/National Healthcare Safety Network definition for probable nosocomial pneumonia
Two or More Serial Chest Radiographs With at Least One of the Following: New or progressive and persistent infiltrate
Consolidation Cavitation
Pneumatoceles, in infantsⱕ1 yr old
(In patients without underlying pulmonary or cardiac disease关e.g., respiratory distress syndrome, bronchopulmonary dysplasia, pulmonary edema, or chronic obstructive pulmonary disease兴, one definitive chest radiograph is acceptable)
PLUS
At Least One of the Following Clinical Criteria:
Fever (⬎38°C or⬎100.4°F) with no other recognized cause for fever Leukopenia (⬍4000 WBC/mm3
) or leukocytosis (ⱖ12,000 WBC/mm3
) For adultsⱖ70 yrs old, altered mental status with no other recognized cause PLUS
At Least Two of the Following Criteria:
New onset of purulent sputum or change in character of sputum or increased respiratory secretions or increased suctioning requirements
New onset or worsening cough, or dyspnea, or tachypnea Rales or bronchial breath sounds
Worsening gas exchange (e.g., oxygen desaturations关e.g., PaO2/FIO2⬍240兴, increased oxygen
requirements, or increased ventilator demand)
WBC, white blood cells.
Table 3. Clinical Pulmonary Infection Score (CPIS) used for the diagnosis of ventilator-associated pneumoniaa
● Temperature, °C
ⱖ36.5 andⱕ38.4⫽0 point ⱖ38.5 andⱕ38.9⫽1 point ⱖ39 orⱕ36⫽2 points ● Blood leukocytes, mm3
ⱖ4000 andⱕ11,000⫽0 point
⬍4000 or⬎11,000⫽1 point⫹band forms ⱖ500⫽ ⫹1 point
● Tracheal secretions
⬍14⫹of tracheal secretions⫽0 point ⱖ14⫹of tracheal secretions⫽1 point⫹
purulent secretion⫽ ⫹1 point ● Oxygenation: PaO2/FIO2
⬎240 or ARDS⫽0 point
ⱕ240 and no evidence of ARDS⫽2 points ● Pulmonary radiograph
No infiltrate⫽0 point
Diffused (or patchy) infiltrate⫽1 point Localized infiltrate⫽2 points ● Culture of tracheal aspirate
(semiquantitative: 0–1–2 or 3⫹) Pathogenic bacteria culturedⱕ1⫹or no
growth⫽0 point
Pathogenic bacteria cultured⬎1⫹ ⫽1 point⫹
same pathogenic bacteria seen on the Gram-negative stain⬎1⫹ ⫽ ⫹1 point
ARDS, acute respiratory distress syndrome.
aTotal points⫽ CPIS (varies from 0 to 12
tivity range, 43% to 83%; specificity
range, 67% to 91%) (25). Similar
diag-nostic accuracy has been demonstrated
by other investigators (26 –32) employing
histologic criteria as a reference
stan-dard. Fa`bregas et al also showed that
ad-dition of the results of quantitative
cul-tures to clinical criteria (CPIS) did not
increase the accuracy of CPIS in
diagnos-ing VAP (11). The available evidence
sug-gests that there is no one absolute gold
standard for the diagnosis of VAP.
How-ever, the clinical relevance of appropriate
antibiotic treatment for VAP supports a
definition employing lower respiratory
tract microbiology as opposed to clinical
criteria alone (3).
Biomarkers.
Several studies (33–35)
have demonstrated that procalcitonin
(PCT) may be helpful in differentiating
bacterial infections from other
inflamma-tory conditions (i.e., acute respirainflamma-tory
distress syndrome, autoimmune diseases)
or nonbacterial infectious (i.e., viral)
dis-eases. Therefore, PCT monitoring may be
useful to limit the overuse of antibiotics
as well as contribute to an early
evalua-tion of disease severity for patients with
pneumonia (35–37). High levels of PCT at
admission and on day 3 seem to be a good
predictor of treatment failure in patients
with a respiratory infection, whereas a
reduction of PCT to low levels supports a
clinical response and ability to shorten or
discontinue antibiotics (37, 38). The use
of PCT to limit unnecessary antibiotics
has most extensively been evaluated in
patients with community-acquired
pneu-monia (36, 37). In a recent study, Briel et
al (38) randomized patients to either a
PCT-guided approach to antibiotic
ther-apy or to a standard approach. For
pa-tients randomized to PCT-guided
ther-apy,
the
use
of
antibiotics
was
discouraged based on levels (PCT level,
ⱕ
0.1 or
ⱕ
0.25
g/L, respectively) or
en-couraged (PCT level,
⬎
0.25
g/L). With
PCT-guided therapy, the antibiotic
pre-scription rate was 72% lower (95%
con-fidence interval, 66% to 78%) than with
standard therapy. These types of
investi-gations suggest that PCT-guided therapy
can reduce antibiotic use for respiratory
tract infections in the outpatient setting
without compromising patient outcomes.
Similar preliminary results have been
observed for the use of PCT in NP
al-though the findings have been mixed.
Ramirez et al (39) found that sequential
PCT measurements had the best
sensitiv-ity and specificsensitiv-ity for VAP compared with
C-reactive protein and the CPIS.
How-ever, Luyt et al (40) demonstrated that
PCT levels and the increase in PCT
com-pared with baseline had poor diagnostic
value for VAP. Although PCT levels may
not be accurate for the diagnosis of VAP,
emerging data (41) suggested that serial
PCT measurements may be used as a
marker to terminate antimicrobial
ther-apy and as a biomarker for sepsis.
Recommendations for Diagnostic
Ap-proach.
As none of the currently available
diagnostic tests provides an absolute
ac-curate diagnosis of VAP when used alone,
a strategy that combines diagnostic
modal-ities is advocated. Patients with suspected
VAP should undergo an evaluation that is
supported by local expertise and should
in-clude imaging procedures (chest
radio-graph, computed tomography),
bacterio-logic cultures from the lower respiratory
tract, and possibly biomarkers. The results
of this evaluation can be used to determine
the likelihood that VAP is present and to
guide therapy in a manner that attempts to
optimize patient outcomes (Fig. 1).
Ensur-ing timely administration of appropriate
antimicrobial therapy optimizes patient
outcomes, whereas avoiding unnecessary
antibiotic exposure minimizes the
emer-gence of antimicrobial resistance. For
un-stable patients, delays in the initiation of
appropriate antibiotic therapy should be
avoided as they are associated with
in-creased mortality (42). Therapy should not
be postponed for the purpose of performing
diagnostic studies in these patients.
Alter-natively, in stable patients, performance of
lower respiratory tract sampling (BAL,
pro-tected specimen brush) has been shown to
reduce antibiotic use in patients with
sus-pected VAP (43– 45).
A meta-analysis (46) of four randomized
studies with a total of 628 patients showed
that invasive strategies for the diagnosis of
VAP did not alter mortality. In a
multi-center trial, The Canadian Critical Care
Tri-als Group (47) randomized 740
mechani-cally ventilated patients who had suspected
VAP after 4 days in the ICU to undergo
either BAL with quantitative cultures or
endotracheal aspiration with
nonquantita-tive culture of the aspirate. There was no
significant difference between study arms
in clinical outcomes or the use of
antibiot-ics. The most likely explanation for the
ob-served lack of effect on outcome was that
prompt appropriate initial antimicrobial
treatment was the crucial issue affecting
survival, and it was not influenced by lower
respiratory tract sampling. As invasive
sam-pling for suspected VAP does not directly
affect the initial antibiotic prescription, it is
not surprising that it does not alter
mor-tality (48). The results of lower respiratory
tract cultures are principally used to
facili-tate modification of the initial
antimicro-bial regimen, either de-escalation if the
pa-tient is improving or escalation of
treatment if the initial regimen was
inap-propriate for the offending pathogen (49,
50).
Prevention of NP
Pharmacologic Approaches to Prevent
NP (Table 4)
Iseganan is an antimicrobial peptide
with activity against Gram-positive
bacte-ria, Gram-negative bactebacte-ria, and yeast. In a
multicenter randomized trial, topical
oro-pharyngeal administration of iseganan was
not associated with a reduction of VAP (51).
Orodigestive decontamination (ODD)
describes the use of a prophylactic
anti-microbial regimen that includes
nonab-sorbable antibiotics applied to the
oro-pharynx and gastrointestinal tract along
with a short course of intravenous
anti-biotics. ODD has been studied for
⬎
25
yrs and
⬎
10 meta-analyses have been
au-thored (52). Despite fairly consistent
demonstration of modest decreases in
mortality and decreases in bloodstream
infections, ODD is not in widespread use.
This is primarily due to concerns of
pro-moting antimicrobial resistance and
un-certain cost-effectiveness. A large
random-ized trial of
⬎
6,000 patients was recently
published comparing ODD, oral
decontam-ination with only topical agents, and
dard care (53). When compared with
stan-dard care, the use of ODD led to a 28-day
mortality decrease from 27.5% to 26.9%.
The 28-day mortality in the oral
decontam-ination group was similar to the ODD
group at 26.6%. Because antimicrobial
re-sistance may take time to develop, its
emer-gence may not be noticed in clinical trials,
and this remains a major concern with the
widespread implementation of ODD.
Like the use of ODD, oral
chlorhexi-dine administration has been associated
with reductions in nosocomial infections,
including VAP, primarily in patients
un-dergoing cardiac surgery (54, 55).
standard therapy (3). Several small
studies (56, 57) have been published in
support of the use of inhaled antibiotics
for both VAP and tracheobronchitis.
Al-though promising, current data are
lacking to support the use of inhaled
antibiotics as more than an adjunctive
therapy in nonimproving patients.
Prolonged courses of intravenous
an-tibiotics can be associated with the
emer-gence of antibiotic resistance; therefore,
their use should be limited to treatment
indications. One study of cefuroxime
ad-ministration for 24 hrs at the time of
intubation in patients with closed-head
injury was associated with a significant
reduction in early-onset VAP (58).
Significant debate has occurred in the
past regarding the role of stress ulcer
prophylaxis as a promoter for the
occur-rence of VAP (59). Nevertheless, no
con-vincing evidence exists to recommend
one agent over another when stress ulcer
prophylaxis is deemed clinically
neces-sary (60).
Available evidence suggests that
shorter courses of antibiotic therapy for
VAP are clinically effective and associated
with less emergence of antibiotic
resis-tance (61– 63). When clinically
accept-able, a 7- to 8-day course of antibiotic
therapy should be considered adequate
for patients demonstrating a clinical
re-sponse to treatment.
Based on the available medical
evi-dence, the routine use of antibiotic
cy-cling or rotation for the prevention of
VAP cannot be recommended (64 – 66).
Transfusion of red blood cells has been
associated with the development of
nos-ocomial infections, including VAP (67–
69). Restricted use of red blood cell
trans-fusion seems appropriate to minimize
this risk, according to available
transfu-sion recommendations (70).
should follow national recommendations
regarding vaccination policies and
che-moprophylaxis to minimize the impact of
respiratory illness outbreaks in the
com-munity (73).
Nonpharmacologic Approaches to
Prevent NP (Table 5)
The endotracheal tube plays an
impor-tant role in the pathogenesis of VAP and
has led some authors to rename this
nos-ocomial infection as “endotracheal
tube-associated pneumonia” (74). Avoidance of
endotracheal intubation using mask
ven-tilation has been shown to reduce the
occurrence of VAP and nosocomial
sinus-itis (75–77).
Reintubation is associated with an
in-creased risk of developing VAP by
facilitat-ing aspiration (78). Appropriate
interven-tions and surveillance should be in place to
minimize unnecessary reintubation.
Unnecessary patient transports out of
the ICU should be avoided as they have
been associated with the occurrence of
VAP (79).
Orotracheal and orogastric intubation
has been associated with reduced
inci-dences of VAP and nosocomial sinusitis
(80, 81). Therefore, the oral route is
pre-ferred when intubations of the trachea
and esophagus are necessary in a
criti-cally ill patient.
Increased manipulation and changing
of ventilator circuits may promote
aspi-ration and increase the occurrence of
VAP (82, 83). Therefore, ventilator circuit
changes should only occur when the
cir-cuit is damaged or visibly soiled. When
significant condensate accumulates within
a ventilator circuit, it should be removed to
avoid aspiration and VAP (84).
Use of heat-moisture exchangers for
humidification has not been shown to
consistently reduce the occurrence of
VAP compared with water humidification
methods (85– 87). Therefore, their use is
left to the treating physicians. More
pro-longed use of heat-moisture exchangers
has not been associated with an increased
risk of VAP (88, 89).
Based on clinical studies, closed and
open endotracheal suctioning systems
have similar rates of VAP associated with
their use (90, 91). However, closed
sys-tems are associated with less
aerosoliza-tion of potentially infected airway
secre-tions. Additionally, the available evidence
(92) suggested that closed suctioning
sys-tems only need to be changed when
mal-functioning or visibly soiled.
Aspiration of subglottic secretions
with a specially designed endotracheal
tube has been associated with reductions
in VAP (93–95). However, sublglottic
suc-tioning has been associated with mucosal
injury of the trachea and failure to
aspi-rate secretions due to either increased
viscosity or mucosal blockage of the
suc-tion port (96, 97).
The development of VAP has been
as-sociated with the duration of mechanical
ventilation (98). Therefore, efforts aimed
at reducing the duration of mechanical
ventilation by optimizing weaning
at-tempts and use of sedation should be
routinely employed (99, 100).
Inadequate staffing of ICUs has been
associated with excess development of
nosocomial infections and prolonged
du-rations of mechanical ventilation (101,
102). Therefore, adequate staffing should
be in place to ensure that protocols are
followed to prevent VAP and other
noso-comial infections, as well as to minimize
patient exposure to mechanical
ventila-tion.
Biofilm formation is an important
pathogenic element in the development
of VAP (103). Clinical investigations (104,
105) suggested that a silver-coated
endo-tracheal tube is safe and can reduce the
occurrence of VAP by almost 50% during
the first 10 days of mechanical
ventila-tion.
Table 4. Pharmacologic-based strategies for VAP prevention
Strategy Recommendation
Evidence
Level Reference(s)
Topical iseganan No 1 51
Orodigestive decontamination (topical/topical plus intravenous antibiotics)
No recommendation 1 52, 53
Oral chlorhexidine Yes 1 54, 55 Aerosolized antibiotics No recommendation 1 56, 57 Intravenous antibiotics No recommendation 1 58 Specific stress ulcer prophylaxis regimen No 1 60 Short-course antibiotic therapy (when
clinically applicable)
Yes 1 61–63
Routine antibiotic cycling/rotation/heterogeneitya No 2 64–66
Restricted (conservative) blood transfusion Yes 2 67–69 Vaccines (influenza, pneumococcal)b Yes 1 71, 72
VAP, ventilator-associated pneumonia.
a
May be useful in specific clinical circumstances (as an adjunct to controlling an outbreak of a multidrug-resistant bacterial infection);b
general recommendation without specific evidence for VAP. Evidence levels: 1, supported by randomized trials; 2, supported by prospective or retrospective cohort studies; 3, supported by case series.
Table 5. Nonpharmacologic-based strategies for VAP prevention
Strategy Recommendation Evidence Level Reference
Use of noninvasive mask ventilation Yes 1 75–77 Avoid reintubation Yes 2 78 Avoid patient transports Yes 2 79 Orotracheal intubation preferred Yes 1 80 Orogastric intubation preferred Yes 2 81 Routine ventilator circuit changes No 1 82, 83 Use of heat-moisture exchanger Yes 1 85–87 Closed endotracheal suctioning Yes 1 90, 91 Subglottic secretion drainage Yes 1 93–95 Shortening the duration of mechanical
ventilation
Yes 1 99, 100
Adequate intensive care unit staffing Yes 2 101, 102 Silver-coated endotracheal tube Yes 1 104, 105 Polyurethane endotracheal tube cuff Yes 1 106, 107 Semierect positioning Yes 1 108, 109 Rotational beds Yes 1 110–112 Chest physiotherapy No 1 113–115 Early tracheostomy No recommendation 1 116–118 Use of protocols/bundles Yes 2 119–121
VAP, ventilator-associated pneumonia.
Endotracheal tube cuffs made of
ultra-thin polyurethane—as compared with
polyvinyl chloride—theoretically reduce
channel formation and minimize the
vol-ume of secretions microaspirated around
the endotracheal cuff. Limited data from
select populations have demonstrated
ef-ficacy (106, 107).
Supine positioning facilitates
aspira-tion in the intubated patient and should
be avoided if clinically possible (108).
However, achieving head elevation to 45°
may be difficult in many clinical
situa-tions. Under those circumstances, the
head of the bed should be raised to the
highest level applicable (109).
Several small trials have shown that
rotating beds can reduce the occurrence
of VAP (110 –112). However, due to the
cost of these beds and selected
popula-tions studied, their use should be based
on perceived benefit and available
re-sources.
Based on the available evidence, the
routine use of chest physiotherapy
can-not be recommended for the prevention
of VAP (113–115).
The timing of tracheostomy may
in-fluence the duration of mechanical
ven-tilation and its associated complications
(116 –118). However, the studies to date
preclude making a definite
recommenda-tion for the prevenrecommenda-tion of VAP.
An increasing body of evidence (119 –
121) suggested that the routine use of
bun-dles or protocols aimed at preventing VAP
can be successful. The challenge of this
approach is to ensure that compliance with
the elements of the bundles and protocols
is adhered to over time in order to sustain
the early observed benefits.
Treatment and prevention
protocols for VAP
Treatment Protocols for VAP:
Appro-priate Initial Therapy and De-Escalation.
The antimicrobial management of VAP is
a balancing act of providing appropriate
initial treatment in a timely manner
based on the knowledge of local
patho-gens and their antimicrobial
susceptibil-ity vs. minimizing further development
of antimicrobial resistance. The latter is
more difficult to achieve and usually
re-quires antimicrobial avoidance. Protocols
aimed at changing from broad- to
nar-row-spectrum antibiotic therapy after
48 –72 hrs of empirical treatment, based
on antimicrobial susceptibility testing,
and using the shortest course of
treat-ment that is clinically acceptable are the
principal strategies of antibiotic
avoid-ance to be employed. The “de-escalation”
strategy attempts to unify these
princi-ples into a single approach that will
op-timize patient outcomes with early
ap-propriate therapy at the same time
minimizing the emergence of antibiotic
resistant pathogens (122).
Failure to provide treatment with an
appropriate initial antimicrobial regimen
for VAP has resulted in significantly
higher rates of septic shock and hospital
mortality (123–125). Additionally,
treat-ment delays of
⬎
24 hrs after meeting
diagnostic criteria for VAP have been
as-sociated with statistically higher rates of
bacteremia and in-hospital mortality
(42). Importantly, adjusting an initial
in-appropriate VAP treatment regimen
ac-cording to subsequent microbiology data
does not result in outcomes equal to
those achieved in patients treated with an
appropriate antimicrobial regimen from
the outset of antibiotic administration
(123, 125). To optimize the likelihood of
prescribing an initial appropriate
regi-men for VAP, the American Thoracic
So-ciety/Infectious Diseases Society of
Amer-ica guidelines (3) for NP recommended a
combination of antimicrobials targeting
the most common bacterial pathogens
associated with early- and late-onset
in-fection. It is important for clinicians to
recognize that the predominant
patho-gens associated with hospital-acquired
infections, including VAP, may vary
be-tween hospitals as well as among
special-ized units within individual hospitals
(126, 127).
The benefits of a protocol for VAP
management was tested in a clinical
set-ting by Ibrahim et al (61), who conducted
a before-and-after study evaluating the
impact of a VAP treatment guideline on
initial administration of appropriate
anti-microbial therapy. In the particular
med-ical ICU where this protocol was
imple-mented,
Pseudomonas aeruginosa
and
methicillin-resistant
Staphylococcus
au-reus
were the most common causes of
VAP. Consequently, the protocol dictated
that the combination of
imipenem-cilastatin, ciprofloxacin, and vancomycin
be prescribed empirically, as this regimen
provided at that time
in vitro
coverage for
⬎
90% of
Pseudomonas aeruginosa
and
100% of methicillin-resistant
Staphylo-coccus aureus
isolates. In cases that had
a bacterial pathogen identified, patients
managed via the protocol were
statisti-cally more likely to receive initial
appro-priate treatment compared with those
treated before protocol implementation
(94% vs. 48%;
p
⬍
.001). Similarly, Wood
and colleagues (128) found that a high
percentage (76%) of critically ill trauma
patients with VAP were prescribed
appro-priate initial antibiotic coverage after
al-tering their clinical pathway based on
historical pathogen incidence.
Lancaster et al (129) also developed a
protocol for the antimicrobial treatment
of HAP based on the American Thoracic
Society/Infectious Diseases Society of
America guidelines. Implementation of
the protocol led to an increase in both the
proportion of patients who received
ap-propriate empirical antibiotic coverage
and appropriate antibiotic de-escalation
according to protocol recommendations.
Similarly, Soo Hoo and colleagues (130)
evaluated the role of a protocol for the
management of severe HAP. Patients
managed with the protocol had a higher
percentage of appropriate initial
treat-ment with a lower mortality rate at 14
days. These studies supported the use of
guidelines as a tool to increase the
appro-priateness of empirical antibiotic therapy
for patients with severe infections, such
as VAP. Similar experiences (131, 132)
have been demonstrated with
standard-ized order sets for the management of
septic shock whose use has also been
associated with improved patient
out-comes.
In a study by Micek and colleagues
(133) at Barnes-Jewish Hospital, patients
with clinically diagnosed VAP were
ran-domly assigned to have the duration of
antibiotic therapy determined by the
clin-ical judgment of the treating physician
(standard therapy) or by a formalized
dis-continuation protocol. Patients assigned
to the discontinuation protocol group
were monitored during the weekday by a
clinical pharmacist who made
recom-mendations to stop one or more
antibi-otics if a noninfectious etiology for
pul-monary infiltrates was identified or if all
of the following criteria were met: 1)
temperature of
⬍
38.3°C; 2) white blood
cell count
⬍
10
⫻
10
3or decreased 25%
from peak value; 3) improvement or lack
of progression of the chest radiograph; 4)
absence of purulent sputum; and 5) PaO
2/
F
IO2ratio of
⬎
250. In the discontinuation
protocol group, 89% of patients had at
least one antibiotic discontinued within
48 hrs of recommendation. The overall
duration of treatment was also
signifi-cantly shorter in the discontinuation
group compared with standard therapy
(6.0
⫾
4.9 days vs. 8.0
⫾
5.6 days;
p
⫽
.001). Singh et al (134) showed similar
results employing the CPIS to assist in
determining an end point for empirical
treatment of VAP.
Prevention Protocols for VAP.
Proto-cols have also been employed successfully
for the prevention of VAP. An
education-based program at Barnes-Jewish Hospital
directed toward respiratory care
practi-tioners and ICU nurses was developed by
a multidisciplinary task force to highlight
correct practices for the prevention of
VAP (120). Each participant was required
to take a preintervention test before
re-viewing a study module and an identical
postintervention test after completing
the study module. After implementation
of the education module, the rate of VAP
decreased to 5.7 per 1000 ventilator days
from 12.6 per 1000 ventilator days (120).
The estimated cost savings secondary to
the decreased rate of VAP for the 12
months post intervention was estimated
to be
⬎
$400,000. This educational
proto-col was then implemented across the four
largest hospitals in the local healthcare
system (119). VAP rates for all four
hos-pitals combined dropped by 46%, from
8.75 per 1000 ventilator days in the year
before the intervention to 4.74 per 1000
ventilator days in the 18 months after the
intervention (
p
⬍
.001). Statistically
sig-nificant decreased rates were observed at
the pediatric hospital and at two of the
three adult hospitals. No change in rates
was seen at the community hospital with
the lowest rate of study module
comple-tion among respiratory therapists (56%).
In addition to showing the effectiveness
of a protocol for VAP prevention, these
studies highlight the importance of
com-pliance with the elements of the protocol
to ensure its success. This same protocol
has also been successfully employed in
the ICUs of a hospital in Thailand (121).
Lansford et al (81) developed a simple
protocol for the prevention of VAP in
trauma patients focusing on head of bed
elevation, oral cleansing with
chlorhexi-dine, a once-daily respiratory
therapist-driven weaning attempt, and conversion
of nasogastric to orogastric feeding tubes.
They found that implementation of the
protocol was associated with a significant
reduction in the rate of VAP. Elements of
this protocol have also been shown to be
effective in other surgical/trauma units
(135). However, compliance with
infec-tion control protocols often wane over
time and can be significantly influenced
by staffing levels in the ICU (136, 137).
Wahl et al (138) have shown that a
com-puterized flow sheet employed in the ICU
could improve compliance with care
measures involved in the prevention of
VAP, as well as other protocols.
Computerized Clinical Decision
Sup-port.
Faced with the complex care
re-quired for patients receiving mechanical
ventilation, computerized clinical
deci-sion support (CCDS) systems have been
increasingly advocated as a means of
maintaining the quality of medical care
(137). Examples of therapies where CCDS
systems have been used to enhance the
implementation of protocols in the ICU
setting include antibiotic therapy,
man-aging ventilatory settings, blood
transfu-sions, glucose control, and traumatic
shock resuscitation (139 –146).
Unfortu-nately, most hospitals do not have the
information systems in place to utilize
CCDS on a routine basis. The main
ad-vantage of CCDS systems in the ICU
set-ting is that they allow the application of
more consistent care (147). Consistent or
protocolized medical care has the
advan-tage of allowing precise changes in the
treatment protocol to occur that can
sub-sequently be assessed in terms of their
impact on clinical outcomes of interest.
It is expected that as advanced
informa-tion systems become more common
place within hospitals, CCDS systems will
also become more widely used as a means
of improving medical practices.
Addition-ally, CCDS systems can be developed that
serve as both early warning systems and
mechanisms for ensuring compliance
with treatment protocols (131, 132, 148).
Conclusion
Optimal management and prevention
of nosocomial infections in the ICU
set-ting are important elements of care for
the critically ill patient. Clinicians need
to develop systems within the ICUs aimed
at optimizing the care of patients in order
to improve their clinical outcomes.
Pro-tocols, standardized order sets,
check-lists, CCDS systems, and clinical practice
teams all provide approaches to the
en-hancement of critical care. Based on
available local expertise and resources, an
approach to quality care improvement in
the ICU should be implemented and
monitored over time. Management and
prevention of nosocomial infections are
one logical area where such systems can
offer an advantage over traditional care
(149, 150).
REFERENCES
1. Hiramatsu K, Niederman MS: Health-care-associated pneumonia: A new therapeutic paradigm.Chest2005; 128:3784 –3787 2. Kollef MH, Shorr A, Tabak YP, et al:
Epide-miology and outcomes of health-care-associated pneumonia: Results from a large US database of culture-positive pneumonia.
Chest2005; 28:3854 –3862
3. American Thoracic society, Infectious Dis-eases Society of America: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and health-care-associated pneumonia. Am J Respir Crit Care Med2005; 71:388 – 416 4. Mandell LA, Wunderink RG, Anzueto A, et
al: Infectious Diseases Society of America/ American Thoracic Society consensus guidelines on the management of commu-nity-acquired pneumonia in adults.Clin In-fect Dis2007; 44:S27–S72
5. Craven DE: What is healthcare-associated pneumonia, and how should it be treated?
Curr Opin Infect Dis2006; 19:153–160 6. Anand N, Kollef MH: The alphabet soup of
pneumonia: CAP, HAP, HCAP, NHAP, and VAP. Semin Respir Crit Care Med 2009; 30:3–9
7. Friedman ND, Kaye KS, Stout JE, et al: Health care–associated bloodstream infec-tions in adults: A reason to change the ac-cepted definition of community-acquired infections. Ann Intern Med 2002; 137: 791–797
algo-rithm. Curr Med Res Opin 2004; 20: 1309 –1320
9. Talwar A, Lee H, Fein A: Community-acquired pneumonia: What is relevant and what is not? Curr Opin Pulm Med 2007; 13:177–185
10. Morrow LE: Prevention strategies for healthcare-associated pneumonia. Semin Respir Crit Care Med2009; 30:86 –91 11. Fa`bregas N, Ewig S, Torres A, et al: Clinical
diagnosis of ventilator associated pneumo-nia revisited: Comparative validation using immediate post-mortem lung biopsies.
Thorax1999; 54:867– 873
12. Rea-Neto A, Youssef NC, Tuche F, et al: Diagnosis of ventilator-associated pneumo-nia: A systematic review of the literature.
Crit Care2008; 12:R56
13. Wunderink RG, Woldenberg LS, Zeiss J, et al: The radiologic diagnosis of autopsy-proven ventilator-associated pneumonia.
Chest1992; 101:458 – 463
14. American Thoracic Society: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and health-care-associated pneumonia. Am J Respir Crit Care Med2005; 171:388 – 416 15. Pingleton SK, Fagon JY, Leeper KV Jr:
Pa-tient selection for clinical investigation of ventilator-associated pneumonia. Criteria for evaluating diagnostic techniques.Chest
1992; 102:553S–556S
16. Centers for Disease Control and Prevention: National Nosocomial Infections Surveil-lance System (NNIS). Available at http:// www.cdc.gov/ncidod/dhqp/nnis.html. Ac-cessed April 12, 2009
17. Miller PR, Johnson JC, Karchmer T, et al: National Nosocomial Infection Surveillance System: From benchmark to bedside in trauma patients.J Trauma2006; 60:98 –103 18. Pugin J, Auckenthaler R, Mili N, et al: Di-agnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic “blind” bronchoal-veolar lavage fluid.Am Rev Respir Dis1991; 143:1121–1129
19. Papazian L, Thomas P, Garbe L, et al: Bron-choscopic or blind sampling techniques for the diagnosis of ventilator-associated pneu-monia. Am J Respir Crit Care Med1995; 152:1982–1991
20. Croce MA, Swanson JM, Magnotti LJ, et al: The futility of the clinical pulmonary infec-tion score in trauma patients. J Trauma
2006; 60:523–527
21. Luyt CE, Chastre J, Fagon JY: Value of the clinical pulmonary infection score for the identification and management of ventila-tor-associated pneumonia. Intensive Care Med2004; 30:844 – 852
22. Schurink CA, Van Nieuwenhoven CA, Ja-cobs JA, et al: Clinical pulmonary infection score for ventilator-associated pneumonia: Accuracy and inter-observer variability. In-tensive Care Med2004; 30:217–224 23. Fartoukh M, Maitre B, Honore S, et al:
Diagnosing pneumonia during mechanical
ventilation: The clinical pulmonary infec-tion score revisited.Am J Respir Crit Care Med2003; 168:173–179
24. Flanagan PG, Findlay GP, Magee JT, et al: The diagnosis of ventilator-associated pneu-monia using bronchoscopic, non-directed lung lavages. Intensive Care Med
2000; 26:20 –30
25. Torres A, Fabregas N, Ewig S, et al: Sam-pling methods for ventilator-associated pneumonia: Validation using different his-tologic and microbiological references.Crit Care Med2000; 28:2799 – 804
26. Balthazar AB, Von NA, De Capitani EM, et al: Diagnostic investigation of ventilator-associated pneumonia using bronchoalveo-lar lavage: Comparative study with a post-mortem lung biopsy.Braz J Med Biol Res
2001; 34:993–1001
27. Torres A, el-Ebiary M, Padro´ L, et al: Vali-dation of different techniques for the diag-nosis of ventilator-associated pneumonia. Comparison with immediate postmortem pulmonary biopsy.Am J Respir Crit Care Med1994; 149:324 –331
28. Torres A, El-Ebiary M, Fa´bregas N, et al: Value of intracellular bacteria detection in the diagnosis of ventilator associated pneu-monia.Thorax1996; 51:378 –384 29. Kirtland SH, Corley DE, Winterbauer RH,
et al: The diagnosis of ventilator-associated pneumonia: A comparison of histologic, mi-crobiologic, and clinical criteria. Chest
1997; 112:445– 457
30. Marquette CH, Copin MC, Wallet F, et al: Diagnostic tests for pneumonia in venti-lated patients: prospective evaluation of di-agnostic accuracy using histology as a diag-nostic gold standard.Am J Respir Crit Care Med1995; 151:1878 –1888
31. Papazian L, Autillo-Touati A, Thomas P, et al: Diagnosis of ventilator-associated pneu-monia: An evaluation of direct examination and presence of intracellular organisms.
Anesthesiology1997; 87:268 –276 32. Rouby JJ, Rossignon MD, Nicolas MH, et al:
A prospective study of protected bronchoal-veolar lavage in the diagnosis of nosocomial pneumonia. Anesthesiology 1989; 71: 679 – 85
33. Christ-Crain M, Muller B: Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators.Eur Respir J2007; 30:556 –573
34. Christ-Crain M, Muller B: Procalcitonin and pneumonia: Is it a useful marker?Curr In-fect Dis Rep2007; 9:233–240
35. Ip M, Rainer TH, Lee N, et al: Value of serum procalcitonin, neopterin, and C-re-active protein in differentiating bacterial from viral etiologies in patients presenting with lower respiratory tract infections. Di-agn Microbiol Infect Dis2007; 59:131–136 36. Christ-Crain M, Jaccard-Stolz D, Bingisser R, et al: Effect of procalcitonin-guided treat-ment on antibiotic use and outcome in lower respiratory tract infections:
Cluster-randomised, single-blinded intervention trial.Lancet2004; 363:600 – 607
37. Christ-Crain M, Stolz D, Bingisser R, et al: Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: A ran-domized trial.Am J Respir Crit Care Med
2006; 174:84 –93
38. Briel M, Schuetz P, Mueller B, et al: Procal-citonin-guided antibiotic use vs a standard approach for acute respiratory tract infec-tions in primary care. Arch Intern Med
2008; 168:2000 –2007
39. Ramirez P, Garcia MA, Ferrer M, et al: Se-quential measurements of procalcitonin levels in diagnosing ventilator-associated pneumonia.Eur Respir J2008; 31:356 –362 40. Luyt CE, Combes A, Reynaud C, et al: Use-fulness of procalcitonin for the diagnosis of ventilator-associated pneumonia.Intensive Care Med2008; 34:1434 –1440
41. Christ-Crain M, Mu¨ller B: Calcitonin pep-tides-the mediators in sepsis or just another fairy tale? Crit Care Med 2008; 36: 1684 –1687
42. Iregui M, Ward S, Sherman G, et al: Clinical importance of delays in the initiation of appropriate antibiotic treatment for venti-lator-associated pneumonia. Chest 2002; 122:262–268
43. Kollef MK, Kollef KE: Antibiotic utilization and outcomes for patients with clinically suspected ventilator-associated pneumonia and negative quantitative BAL culture re-sults.Chest2005; 128:2706 –2713 44. Fagon JY, Chastre J, Wolff M, et al: Invasive
and noninvasive strategies for management of suspected ventilator-associated pneumo-nia. A randomized trial. Ann Intern Med
200018;132:621– 630
45. Heyland DK, Cook DJ, Marshall J, et al: The clinical utility of invasive diagnostic tech-niques in the setting of ventilator-associ-ated pneumonia. Canadian Critical Care Trials Group.Chest1999; 115:1076 –1084 46. Shorr AF, Sherner JH, Jackson WL, et al:
Invasive approaches to the diagnosis of ven-tilator-associated pneumonia: A meta-analysis.Crit Care Med2005; 33:46 –53 47. Canadian Critical Care Trials Group: A
ran-domized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med2006; 355:2619 –2630
48. Kollef MH: Diagnosis of ventilator-associ-ated pneumonia.N Engl J Med2006; 355: 2691–2693
49. Rello J, Vidaur L, Sandiumenge A, et al: De-escalation therapy in ventilator-associ-ated pneumonia.Crit Care Med2004; 32: 2183–2190
50. Leone M, Garcin F, Bouvenot J, et al: Ven-tilator-associated pneumonia: Breaking the vicious circle of antibiotic overuse. Crit Care Med2007; 35:379 –385
52. Liberati A, D’Amico R, Pifferi, et al: Antibi-otic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care.Cochrane Database Syst Rev
2004; 1:CD000022
53. de Smet AM, Kluytmans JA, Cooper BS, et al: Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med2009; 360:20 –31
54. Koeman M, van der Ven AJ, Hak E, et al: Oral decontamination with chlorhexidine reduces the incidence of ventilator-associ-ated pneumonia.Am J Respir Crit Care Med
2006; 173:1348 –1355
55. Segers P, Speekenbrink RG, Ubbink DT, et al: Prevention of nosocomial infection in cardiac surgery by decontamination of the nasopharynx and oropharynx with chlo-rhexidine gluconate: A randomized con-trolled trial.JAMA2006; 296:2460 –2466 56. Palmer LB, Smaldone GC, Chen JJ, et al:
Aerosolized antibiotics and ventilator-associated tracheobronchitis in the inten-sive care unit. Crit Care Med 2008l; 36: 2008 –2013
57. Wood GC, Boucher BA, Croce MA, et al: Aerosolized ceftazidime for prevention of ventilator-associated pneumonia and drug effects on the proinflammatory response in critically ill trauma patients. Pharmaco-therapy2002; 22:972–982
58. Sirvent JM, Torres A, El-Ebiary M, et al: Protective effect of intravenously adminis-tered cefuroxime against nosocomial pneu-monia in patients with structural coma.
Am J Respir Crit Care Med 1997; 155: 1729 –1734
59. Kahn JM, Doctor JN, Rubenfeld GD: Stress ulcer prophylaxis in mechanically venti-lated patients: Integrating evidence and judgment using a decision analysis. Inten-sive Care Med2006; 32:1151–1158 60. Cook D, Guyatt G, Marshall J, et al: A
com-parison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleed-ing in patients requirbleed-ing mechanical venti-lation.N Engl J Med1998; 338:791–797 61. Ibrahim EH, Ward S, Sherman G, et al:
Experience with a clinical guideline for the treatment of ventilator-associated pneumo-nia.Crit Care Med2001; 29:1109 –1115 62. Dennesen PJ, van der Ven AJ, Kessels AG, et
al: Resolution of infectious parameters after antimicrobial therapy in patients with ven-tilator-associated pneumonia.Am J Respir Crit Care Med2001; 163:1371–1375 63. Chastre J, Wolff M, Fagon JY, et al:
Com-parison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: A randomized trial.JAMA2003; 290: 2588 –2598
64. Kollef MH, Vlasnik J, Sharpless L, et al: Scheduled change of antibiotic classes: A strategy to decrease the incidence of venti-lator-associated pneumonia. Am J Respir Crit Care Med1997; 156:1040 –1048 65. Gruson D, Hilbert G, Vargas F, et al:
Rota-tion and restricted use of antibiotics in a
medical intensive care unit. Impact on the incidence of ventilator-associated pneumo-nia caused by antibiotic-resistant Gram-negative bacteria. Am J Respir Crit Care Med2000; 162:837– 843
66. Warren DK, Hill HA, Merz LR, et al: Cycling empirical antimicrobial agents to prevent emergence of antimicrobial-resistant Gram-negative bacteria among intensive care unit patients.Crit Care Med2004; 32: 2450 –2456
67. Shorr AF, Duh MS, Kelly KM, et al: Red blood cell transfusion and ventilator-associated pneumonia: A potential link?
Crit Care Med2004; 32:666 – 674 68. Taylor RW, Manganaro L, O’Brien J, et al:
Impact of allogenic packed red blood cell transfusion on nosocomial infection rates in the critically ill patient. Crit Care Med
2002; 30:2249 –2254
69. Taylor RW, O’Brien J, Trottier SJ, et al: Red blood cell transfusions and nosocomial in-fections in critically ill patients.Crit Care Med2006; 34:2302–2308
70. Marik PE, Corwin HL: Efficacy of red blood cell transfusion in the critically ill: A sys-tematic review of the literature.Crit Care Med2008; 36:2667–2674
71. Nichol KL, Nordin J, Mullooly J, et al: In-fluenza vaccination and reduction in hospi-talizations for cardiac disease and stroke among the elderly. N Engl J Med 2003; 348:1322–1332
72. Klugman KP, Madhi SA, Huebner RE, et al: A trial of a 9-valent pneumococcal conju-gate vaccine in children with and those without HIV infection.N Engl J Med2003; 349:1341–1348
73. Centers for Disease Control and Pre-vention: 2009 H1N1 flu. Available at http://www.cdc.gov/swineflu. Accessed April 27, 2009
74. Pneumatikos IA, Dragoumanis CK, Bouros DE: Ventilator-associated pneumonia or en-dotracheal tube-associated pneumonia? An approach to the pathogenesis and preven-tive strategies emphasizing the importance of endotracheal tube.Anesthesiology2009; 110:673– 680
75. Antonelli M, Conti G, Rocco M, et al: A comparison of noninvasive positive-pres-sure ventilation and conventional mechan-ical ventilation in patients with acute respi-ratory failure. N Engl J Med 1998; 339: 429 – 435
76. Nava S, Ambrosino N, Clini E, et al: Nonin-vasive mechanical ventilation in the wean-ing of patients with respiratory failure due to chronic obstructive pulmonary disease. A randomized, controlled trial. Ann Intern Med1998; 128:721–728
77. Brochard L, Mancebo J, Wysocki M, et al: Noninvasive ventilation for acute exacerba-tions of chronic obstructive pulmonary dis-ease.N Engl J Med1995; 333:817– 822 78. Torres A, Gatell JM, Aznar E, et al:
Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical
ventilation. Am J Respir Crit Care Med
1995; 152:137–141
79. Kollef MH, Von Harz B, Prentice D, et al: Patient transport from intensive care in-creases the risk of developing ventilator-associated pneumonia. Chest 1997; 112: 765–773
80. Holzapfel L, Chastang C, Demingeon G, et al: A randomized study assessing the sys-tematic search for maxillary sinusitis in na-sotracheally mechanically ventilated pa-tients. Influence of nosocomial maxillary sinusitis on the occurrence of ventilator-associated pneumonia. Am J Respir Crit Care Med1999; 159:695–701
81. Lansford T, Moncure M, Carlton E, et al: Efficacy of a pneumonia prevention proto-col in the reduction of ventilator-associated pneumonia in trauma patients.Surg Infect
2007; 8:505–510
82. Kollef MH, Shapiro SD, Fraser VJ, et al: Mechanical ventilation with or without 7-day circuit changes. A randomized con-trolled trial. Ann Intern Med 1995; 123: 168 –74
83. Dreyfuss D, Djedaini K, Weber P, et al: Pro-spective study of nosocomial pneumonia and of patient and circuit colonization dur-ing mechanical ventilation with circuit changes every 48 hours versus no change.
Am Rev Respir Dis1991; 143:738 –743 84. Craven DE, Goularte TA, Make BJ:
Contam-inated condensate in mechanical ventilator circuits. A risk factor for nosocomial pneu-monia? Am Rev Respir Dis 1984; 129: 625– 628
85. Martin C, Perrin G, Gevaudan MJ, et al: Heat and moisture exchangers and vaporiz-ing humidifiers in the intensive care unit.
Chest1990; 97:144 –149
86. Dreyfuss D, Djedaïni K, Gros I, et al: Me-chanical ventilation with heated humidifi-ers or heat and moisture exchanghumidifi-ers: Ef-fects on patient colonization and incidence of nosocomial pneumonia.Am J Respir Crit Care Med1995; 151:986 –992
87. Kollef MH, Shapiro SD, Boyd V, et al: A randomized trial comparing an extended use hygroscopic condenser humidifier to heated humidification in mechanically ven-tilated patients.Chest1998; 113:759 –767 88. Davis K Jr, Evans SL, Campbell RS, et al:
Prolonged use of heat and moisture ex-changers does not affect device efficiency or frequency rate of nosocomial pneumonia.
Crit Care Med2000; 28:1412–1418 89. Thomachot L, Leone M, Razzouk K, et al:
Randomized clinical trial of extended use of a hydrophobic condenser humidifier: 1 vs. 7 days.Crit Care Med2002; 30:232–237 90. Combes P, Fauvage B, Oleyer C:
closed versus an open tracheal suction sys-tem.Crit Care Med2005; 33:115–119 92. Kollef MH, Prentice D, Shapiro SD, et al:
Mechanical ventilation with or without daily in-line suction catheter changes: A randomized controlled trial. Am J Respir Crit Care Med1997; 156:466 – 472 93. Kollef MH, Skubus NJ, Sundt TM: A
ran-domized clinical trial of continuous sub-glottic aspiration in cardiac surgery pa-tients.Chest1999; 116:1339 –1346 94. Valle´s J, Artigas A, Rello J, et al: Continuous
aspiration of subglottic secretions in pre-venting ventilator-associated pneumonia.
Ann Intern Med1995; 122:179 –186 95. Mahul P, Auboyer C, Jospe R, et al:
Preven-tion of nosocomial pneumonia in intubated patients: respective role of mechanical sub-glottic secretions drainage and stress ulcer prophylaxis.Intensive Care Med1992; 18: 20 –25
96. Dragoumanis CK, Vretzakis GI, Papaioan-nou VE, et al: Investigating the failure to aspirate subglottic secretions with the Evac endotracheal tube.Anesth Analg2007; 105: 1083–1085
97. Berra L, De Marchi L, Panigada M, et al: Evaluation of continuous aspiration of sub-glottic secretion in an in vivo study. Crit Care Med2004; 32:2071–2078
98. Cook DJ, Walter SD, Cook RJ, et al: Inci-dence of and risk factors for ventilator-associated pneumonia in critically ill pa-tients.Ann Intern Med1998; 129:433– 440 99. Brook AD, Ahrens TS, Schaiff R, et al: Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation.
Crit Care Med1999; 27:2609 –2615 100. Ely EW, Meade MO, Haponik EF, et al:
Me-chanical ventilator weaning protocols driven by nonphysician health-care profes-sionals: Evidence-based clinical practice guidelines.Chest2001; 120:454S– 463S 101. Needleman J, Buerhaus P, Mattke S, et al:
Nurse-staffing levels and the quality of care in hospitals. N Engl J Med 2002; 346: 1715–1722
102. Thorens JB, Kaelin RM, Jolliet P, et al: In-fluence of the quality of nursing on the duration of weaning from mechanical ven-tilation in patients with chronic obstructive pulmonary disease.Crit Care Med1995; 23: 1807–1815
103. Olson ME, Harmon BG, Kollef MH: Silver-coated endotracheal tubes associated with reduced bacterial burden in the lungs of mechanically ventilated dogs. Chest2002; 121:863– 870
104. Rello J, Kollef M, Diaz E, et al: Reduced burden of bacterial airway colonization with a novel silver-coated endotracheal tube in a randomized multiple-center feasibility study.Crit Care Med2006; 34:2766 –2772 105. Kollef MH, Afessa B, Anzueto A, et al:
Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: The NAS-CENT randomized trial. JAMA 2008; 300: 805– 813
106. Lorente L, Lecuona M, Jimenez A, et al: Influence of an endotracheal tube with polyurethane cuff and subglottic secretion drainage on pneumonia.Am J Respir Crit Care Med2007; 176:1079 –1083
107. Poelaert J, Depuydt P, De Wolf A, et al: Polyurethane cuffed endotracheal tubes to prevent early postoperative pneumonia af-ter cardiac surgery: A pilot study.J Thorac Cardiovasc Surg2008; 135:771–776 108. Drakulovic MB, Torres A, Bauer TT, et al:
Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: A randomised trial. Lan-cet1999; 354:1851–1858
109. van Nieuwenhoven CA, Vandenbroucke-Grauls C, van Tiel FH, et al: Feasibility and effects of the semirecumbent position to prevent ventilator-associated pneumonia: A randomized study.Crit Care Med2006; 34: 396 – 402
110. Fink MP, Helsmoortel CM, Stein KL, et al: The efficacy of an oscillating bed in the prevention of lower respiratory tract infec-tion in critically ill victims of blunt trauma. A prospective study. Chest 1990; 97: 132–137
111. deBoisblanc BP, Castro M, Everret B, et al: Effect of air-supported, continuous, pos-tural oscillation on the risk of early ICU pneumonia in nontraumatic critical illness.
Chest1993; 103:1543–1547
112. Gentilello L, Thompson DA, Tonnesen AS, et al: Effect of a rotating bed on the inci-dence of pulmonary complications in criti-cally ill patients. Crit Care Med1988; 16: 783–786
113. Hall JC, Tarala RA, Tapper J, et al: Preven-tion of respiratory complicaPreven-tions after ab-dominal surgery: A randomised clinical trial.BMJ1996; 312:148 –152
114. Ntoumenopoulos G, Presneill JJ, McEl-holum M, et al: Chest physiotherapy for the prevention of ventilator-associated pneu-monia. Intensive Care Med 2002; 28: 850 – 856
115. Pasquina P, Trame`r MR, Granier JM, et al: Respiratory physiotherapy to prevent pul-monary complications after abdominal sur-gery: A systematic review.Chest2006; 130: 1887–1899
116. Bouderka MA, Fakhir B, Bouaggad A, et al: Early tracheostomy versus prolonged endo-tracheal intubation in severe head injury.
J Trauma2004; 57:251–254
117. Sugerman HJ, Wolfe L, Pasquale MD: Mul-ticenter, randomized, prospective trial of early tracheostomy. J Trauma 1997; 43: 741–747
118. Rumbak MJ, Newton M, Truncale T, et al: A prospective, randomized, study comparing early percutaneous dilational tracheotomy to prolonged translaryngeal intubation (de-layed tracheotomy) in critically ill medical patients. Crit Care Med 2004; 32: 1689 –1694
119. Babcock HM, Zack JE, Garrison T, et al: An educational intervention to reduce
ventila-tor-associated pneumonia in an integrated health system. A comparison of effects.
Chest2004; 125:2224 –2231
120. Zack JE, Garrison T, Trovillion E, et al: Effect of an education program aimed at reducing the occurrence of ventilator-associated pneumonia.Crit Care Med2002; 30:2407–2412
121. Apisarnthanarak A, Pinitchai U, Thongphu-beth K, et al: Effectiveness of an educational program to reduce ventilator-associated pneumonia in a tertiary care center in Thai-land: A 4-year study.Clin Infect Dis2007; 45:704 –711
122. Kollef MH: Optimizing antibiotic therapy in the intensive care unit setting. Crit Care
2001; 5:189 –195
123. Kollef MH, Ward S: The influence of mini-BAL cultures on patient outcomes: Implica-tions for the antibiotic management of ven-tilator-associated pneumonia. Chest 1998; 113:412– 420
124. Luna CM, Vujacich P, Niederman MS, et al: Impact of BAL data on the therapy and outcome of ventilator-associated pneumo-nia.Chest1997; 111:676 – 685
125. Alvarez-Lerma F: Modification of empiric antibiotic treatment in patients with pneu-monia acquired in the intensive care unit. ICU-Acquired Pneumonia Study Group. In-tensive Care Med1996; 22:387–394 126. Namias N, Samiian L, Nino D, et al:
Inci-dence and susceptibility of pathogenic bac-teria vary between intensive care units within a single hospital: Implications for empiric antibiotic strategies. J Trauma
2000; 49:638 – 645
127. Rello J, Sa-Borges M, Correa H, et al: Vari-ations in etiology of ventilator-associated pneumonia across four treatment sites: Im-plications for antimicrobial prescribing practices.Am J Respir Crit Care Med1999; 160:608 – 613
128. Wood GC, Mueller EW, Croce MA, et al: Evaluation of a clinical pathway for ventila-tor-associated pneumonia: Changes in bac-terial flora and the adequacy of empiric an-tibiotics over a three-year period. Surg Infect2005; 6:203–213
129. Lancaster JW, Lawrence KR, Fong JJ, et al: Impact of an institution-specific hospital-acquired pneumonia protocol on the appro-priateness of antibiotic therapy and patient outcomes. Pharmacotherapy 2008; 28: 852– 862
130. Soo Hoo GW, Wen E, Nguyen TV, et al: Impact of clinical guidelines in the manage-ment of severe hospital-acquired pneumo-nia.Chest2005; 128:2778 –2787
131. Micek ST, Roubinian N, Heuring T, et al: Before-after study of a standardized hospital order set for the management of septic shock.Crit Care Med2006; 34:2707–2713 132. Thiel SW, Asghar MF, Micek ST, et al:
133. Micek ST, Ward S, Fraser VJ, et al: A ran-domized controlled trial of an antibiotic dis-continuation policy for clinically suspected ventilator-associated pneumonia. Chest
2004; 125:1791–1799
134. Singh N, Rogers P, Atwood CW, et al: Short-course empiric antibiotic therapy for pa-tients with pulmonary infiltrates in the in-tensive care unit. A proposed solution for indiscriminate antibiotic prescription.Am J Respir Crit Care Med2000; 162:505–511 135. Sona CS, Zack JE, Schallom ME, et al: The
impact of a simple, low-cost oral care pro-tocol on ventilator-associated pneumonia rates in a surgical intensive care unit.J In-tensive Care Med2009; 24:54 – 62 136. DuBose JJ, Inaba K, Shiflett A, et al:
Mea-surable outcomes of quality improvement in the trauma intensive care unit: The im-pact of a daily quality rounding checklist.
J Trauma2008; 64:22–27
137. Kollef MH: Prevention of hospital-associ-ated pneumonia and ventilator-associhospital-associ-ated pneumonia. Crit Care Med 2004; 32: 1396 –1405
138. Wahl WL, Talsma A, Dawson C, et al: Use of computerized ICU documentation to
cap-ture ICU core measures.Surgery2006; 140: 684 – 689
139. Sucher JF, Moore FA, Todd SR, et al: Com-puterized clinical decision support: A tech-nology to implement and validate evidence based guidelines. J Trauma 2008; 64: 520 –537
140. Pestotnik SL, Classen DC, Evans RS, et al: Implementing antibiotic practice guidelines through computer-assisted decision sup-port: Clinical and financial outcomes.Ann Intern Med1996; 124:884 – 890
141. Thomsen GE, Pope D, East TD, et al: Clin-ical performance of a rule-based decision support system for mechanical ventilation of ARDS patients.Proc Annu Symp Comput Appl Med Care1993: 339 –343
142. McKinley BA, Moore FA, Sailors RM, et al: Computerized decision support for me-chanical ventilation of trauma induced ARDS: Results of a randomized clinical trial.J Trauma2001; 50:415– 424 143. Nasraway SA Jr: Hyperglycemia during
crit-ical illness.JPEN J Parenter Enteral Nutr
2006; 30:254 –258
144. Evans RS, Pestotnik SL, Classen DC, et al: A computer-assisted management program
for antibiotics and other antiinfective agents.N Engl J Med1998; 338:232–238 145. East TD, Heermann LK, Bradshaw RL, et al:
Efficacy of computerized decision support for mechanical ventilation: Results of a pro-spective multi-center randomized trial.
Proc AMIA Symp1999:251–255
146. McKinley BA, Sailors RM, Glorsky SL, et al: Computer directed resuscitation of major torso trauma.Shock2001; 15:S46 147. Santora RJ, McKinley BA, Moore FA:
Com-puterized clinical decision support for trau-matic shock resuscitation.Curr Opin Crit Care2008; 14:679 – 84
148. Thiel SW, Rosini JM, Shannon W, et al: Early prediction of septic shock in hospital-ized patients.J Hosp Med2010; 5:19 –25 149. Paul M, Nielson AD, Goldberg E: Prediction
of specific pathogens in patients with sepsis: evaluation of TREAT, a computerized deci-sion support system. J Antimicrob Che-mother2007; 59:1204 –1207
