CHEST

VOLUME 108 / NUMBER 2 / AUGUST, 1995 SUPPLEMENT

Epidemiology of Nosocomial Pneumonia*

New

Perspectives on an Old Disease

Donald E. Craven, MD; and Kathleen A.

Steger, RN, MPH

(CHEST 1995; 108:1S-16S)

"Keep an open mind toward pneumonia. Our grandchildren
will be interested and are likely to have as many differences
of opinion as we have."

NOSOCOMIAL PNEUMONIA

..

William Osier, circa 1900

As Osier predicted nearly a century ago, controversies

^**

persist over the epidemiology, pathogenesis, and

prevention of nosocomial pneumonia.12 Hospital-ac
quired pneumonia is now the second most common
nosocomial infection in the US and is associated with

high
morbidity, mortality, and increased hospital
cost.1"4 Nosocomial pneumonia has been defined as an
infection of lung parenchyma that was neither present
nor incubating at the time of hospital admission. This
definition, however, may exclude cases that occur in
the outpatient setting, or after discharge from the
hospital.5 Nosocomial pneumonia is usually caused by
bacteria, but cases due to Legionella, Mycobacterium
tuberculosis, viruses, or fungi deserve special atten
tion.2,6"8 Furthermore, routes of infection and preven
tion strategies vary considerably among causataive
agents.
Accurate diagnosis is critical to understand epide
and prevention of hospital-ac
miology, pathogenesis,Most
quired
pneumonia.9,10 cases of nosocomial pneu
monia occur in nonventilated patients and are diag
nosed clinically, but the rate of pneumonia is higher in
mechanically ventilated patients. The latter group may
be diagnosed clinically, by bronchoscopy or "blind"
BAL or protected specimen brush (PSB), and more
recently
by quantitative endotracheal aspirates.9"13
This article will discuss the epidemiology of noso
comial pneumonia. Special emphasis will be directed
toward bacterial causes, new risk factors, and emerg
ing pathogens.
Bacterial Pneumonia

Etiologic Agents
agents causing nosocomial pneumonia
Etiologic
differ
may
by hospital, patient population, and the
*From the Departments of Medicine and Epidemiology, Boston
University Schools of Medicine and Public Health, Division of

Infectious Diseases, Maxwell Finland Laboratory for Infectious

Diseases, Boston City Hospital, Boston.

Figure 1. The "iceberg" of nosocomial pneumonia emphasizing

that many cases are not diagnosed or are misclassified. Those cases
that are not diagnosed may have been misclassified as communityacquired, become manifest only at postmortem, may have occurred
in outpatient setting, or after discharge from hospital. Furthermore,
transmission of S pneumoniae, H influenzae, and PCP in
possible
a hospital setting is not widely appreciated. Reproduced from Cra
ven and Steger.

methods employed.2,6,14"19 The oc

specific diagnostic
of pneumonia after discharge and decreasing
autopsy rates in the US probably result in an underes
timate of the crude and organism-specific rates of
nosocomial pneumonia (Fig l).5 Although bacteria are
most commonly isolated, diagnostic cultures for vicurrence

SOURCES OF INFECTION
DEVICES

ENVIRONMENT
AIR: ASPERGILLUS
WATER: LEGIONELLA
FOOD: ENTERIC GNB
F0MITES: S. AUREUS
RSV

\ /

ft

OTHER PATIENTS

ENDOTRACHEAL TUBE
SUCTION CATHETERS
BRONCHOSCOPE
RESPIRATORY THERAPY

EQUIPMENT

NASOGASTRIC TUBE

STAFF

INFLUENZA RSV
H. INFLUENZAE
S. AUREUS
P. AERUGINOSA
MDR STRAINS
Figure 2. Modes oi transmission of various nosocomial respiratory
tract
Microorganisms may originate from the environ
staff.
ment, invasive devices, or from other patients or
,

pathogens.

hospital

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Table 1.Common Pathogens Currently Associated With Nosocomial Pneumonia*

Pathogen

Early

onset

Frequency, %

Source of Organism

bacteria pneumonia

S pneumoniae

H influenzae
Late onset bacterial pneumonia

Aerobic Gram-negative bacilli

5-20

Endogenous
Respiratory droplet

Other patients

<5-15
=20-60

P aeruginosa

Endogenous

Enterobacter spp
Acinetobacter spp

Other patients
Environment

K pneumoniae
S marcescens
E coli

Enteral feeding
Health-care workers

Equipment/devices
Endogenous

Gram-positive cocci
S aureus

20-40

Health-care workers

Early and late onset pneumonia

Anaerobic bacteria
L pneumophila

Environment

0-35

Endogenous

0-10

Potable water

Showers, faucets

Cooling towers
Endogenous
Other patients/staff
Other patients/staff
Other patients/staff

M tuberculosis

Viruses

Influenza A and B

Respiratory syncytial virus

<1
<1

Fomites

Fungi/Protozoa
Aspergillus
Candida spp

P carinii

<1
<1

Air, construction

Endogenous
Endogenous

Other patients/staff

<1

Other patients
*Crude rates of pneumonia may vary by hospital, patient population, and method of diagnosis. Adapted, in part from references 3, 19, & 35.

and fungi are not rou

Legionella, anaerobes,
in
Bacteria
tinely performed many hospitals.2,20,21
from
nosocomial
several
causing
pneumonia originate
different sources, including the patient's endogenous
flora, other patients, staff, contaminated devices, or the
environment (Fig 2).22,23
Time of onset of the pneumonia, prior hospitaliza
tion, and previous antibiotic therapy are also impor
tant. Early onset bacterial nosocomial pneumonia oc
curs during the first 4 days of the hospital stay and is
more frequently caused by Streptococcus pneumonia,
Moraxella catarrhalis, or Haemophilus influenzae (Ta
ble l).15'24"28 Conversely, late-onset bacterial pneumo
nia occurs after 4 days and is more commonly caused
by Klebsiellaor or Acinetobacter spp, Pseudomonas
aeruginosa, Staphylococcus aureus.24'27 Gram-neg
ative bacilli have been implicated in more than 60% of
reported cases, many in which patients are hospitalized
in university hospitals and are mechanically ventilated.
S aureus varies from 20 to 40% and like Gram-nega
tive bacilli rates, depends on the population studied,
method of diagnosis, and time of onset of the pneu
monia
ruses,

(Table 2).29,30

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Because critically ill patients may have both acute

and chronic severe underlying diseases, receive multi
ple antibiotics, and have numerous invasive devices,

are susceptible to multidrug-resistant (MDR)

they
strains.22,23 In a recent study, Rello and coworkers29
compareddue
patients with ventilator-associated pneumo
nia
to

(VAP)

methicillin-sensitive S aureus (MSSA)

to patients with VAP due to methicillin-resistant S au

reus (MRSA). Patients with VAP due to MRSA were
more
to have received prior steroids,

significantly

likely

mechanical ventilation for more than 6 days, be older

than 25 years, to have pre-existing chronic lung disease
and prior antibiotic therapy. In addition, the frequency
of bacteremia, shock, and subsequent mortality were
higher in the MRSA group compared to the patients
with VAP due to MSSA.
Many cases of bacterial nosocomial pneumonia are
polymicrobial.15,18,24,27,31"33 The
specific etiology, how
ever, may vary depending on whether the patient is
intubated, in the ICU, or time of onset1*17,28'34,35
(Table 2). In a recent series of patients in communitybased teaching hospitals studied by Schleupner and
Cobb,28 51% of the 231 episodes of nosocomial pneuContemporary Issues in Pulmonary Infections

Table 2.Microorganisms Isolated from Respiratory Tract Specimens Obtained by Various Representative Methods
From Adult Patients with a Diagnosis of Nosocomial Pneumonia

Schaberg35

Bartlett17

Fagon15

Torres1

Hospital type

NNIS & UMH*

Veterans

General

General

Ventilated or nonventilated
Number
Number of episodes of pneumonia
Specimen(s) cultured

Mixed

Mixed

Ventilated

Ventilated
78
78
Protected specimen

Patients studied

N/Af

159
159

N/A

Transtracheal

Sputum, tracheal
aspirate

aspirate, pleural
fluid, blood

49
52

Protected

specimen

brushing

brushing, lung
aspirate, pleural
fluid, blood

Culture results
No organism isolated

N/A
N/A

Number of isolates
Aerobic bacteria
Gram-negative bacilli

15,499

Polymicrobial

P aeruginosa

Enterobacter sp
Klebsiella sp
E coli
Serratia sp
Proteus sp
Citrobacter sp
Acinetobacter calcoaceticus
Others

314

Legionella sp
Gram-positive cocci
S aureus
Streptococcus sp

11

4
23
14
0
11
0
0
0

0
15

15
0

0
0
0
1
1
0
9
0

17%M

10% M

0%1

N/A

2%"
52%"
33%"

2%'

7
6
5
3
1
N/A
N/A

17%*
6%*

Peptostreptococcus
Fusobacterium sp
Peptococcus sp
Bacteroides melaninogenicus
B fragilis
Fungi
Aspergillus sp
Candida sp

Viruses

56%"
25%"
31
0

1
0
N/A
N/A
N/A
N/A
N/A
N/A

35%"
14%"
10
11

4%*

N/A
N/A
N/A
N/A

N/A

4%*
N/A

*NNIS & UMH=National Nosocomial Infections Surveillance

*N/A=Not applicable: not tested or not reported.

N/A

46%"
9%M

N/A

Others
Anaerobes

111

50%$
17%*

6%*

H influenzae

54%*
13%*

54%*

75%"
31%"
2
4

21

2%"
N/A
N/A
N/A
N/A
N/A
0
0
0
N/A

16% 1

5%'

2
0
0
0
0
0
0
0

1%'
1%1
0
N/A

System and University of Michigan Hospitals.

* Percent episodes.
Percent isolates.

'Percent episodes (percentages not additive due to polymicrobial etiology in some episodes).
^Percent patients with pure culture.
Adapted from Tablan et al.2

by

monia were caused S pneumoniae (pneumococcus)

H influenzae, and only 26% were due to Gramnegative bacilli. This is in sharp contrast to reports from
university hospitals or studies of mechanically venti
lated patients in whom Gram-negative bacilli and S
or

aureus

predominate.15,32

Rates of Nosocomial Pneumonia

Nosocomial pneumonia accounts for 13 to 18% of

nosocomial infections and occurs at a frequency of 4 to
7 episodes per 1,000 hospitalizations in nonteaching
and university hospitals, respectively.2,3 Lower respi

ratory tract infection is diagnosed in 0.8 to 0.9% of

medical and surgical patients, 17.5% of postoperative
patients, and in 7% of neonatal ICU patients.3,36"38
Several studies have indicated that approximately 10 to
25% of ICU patients develop pneumonia.
The incidence of VAP ranges from 6 to 30 cases per
100 patients, depending on the population stud
ied.1^39-41 Rates of pneumonia are increased 4- to 21fold for intubated patients.37,42,43 However, in patients
receiving mechanical ventilation, overall rates fail to
adjust for time or duration of mechanical ventilation,
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as has been used for assessing the risks associated with

other medical devices. Using a formula of "cases per
1,000 ventilator days" is more useful for more consis
tent analysis of VAP rates. Rates of pneumonia per
1,000 ventilator days range from 5 in pediatric inten
sive care units in the National Nosocomial Infection
Study to 34 in patients with thermal injury.2,40,44 Rates
of VAP per 1,000 ventilator days are approximately 15
per 1,000 for medical and surgical ICU patients; rates
are often higher in surgical intensive care than the
medical ICU patients.40,45"47 Crude rates of VAP are in
the range of 1 to 3% per day of intubation and
mechanical ventilation.46,47 Rates of nosocomial pneu
monia may be skewed by the fact that many studies
have been conducted in high-risk populations hospi
talized in university teaching hospitals rather than

community hospitals or long-term care facilities.28,48

Mortality
The crude mortality rates for nosocomial pneumo

nia range from 20 to 50% and reflect, in part, the

of
studied.33,41,49"53 In a case control
population
200 patients who died in the hospital, nosocomial

study

pneumonia contributed to 60% ofthe infection-related

deaths.54 On examination of 1,000 autopsy reports,
pneumonia was associated with 7.5% of the deaths and
was the most common nosocomial infection contrib
uting to death.55 Mortality rates were usually higher in
persons with pneumonia due to P aeruginosa, and
when secondary bacteremia was preSent.1,37,47,51,52,55,56
ICU patients with nosocomial pneumonia appear to
have a twofold to tenfold increased risk of mortality
In
compared toriskpatients without
pneumonia.34,47,50,51
for
in
factors
nonventilated
pneumonia
dependent
patients include "high-risk" organisms, bilateral infil
trates on chest radiograph, and respiratory failure.34 By
comparison, risk factors for mechanically ventilated
patients include the following: transfer from another
duration of mechanical
hospital or ward, renal failure,
on
ventilation, pneumonia admission, coma, severe
underlying disease, worsening respiratory failure,
shock, inappropriate antibiotic treatment, and hospi

talization in noncardiac ICU.34,50 Of note is that VAP

significantly associated with mortality but was not
independent
predictor of mortality.50
In contrast to crude mortality, the mortality attrib
utable to pneumonia, or "attributable mortality" for
nosocomial pneumonia was reported to be 30 to
33% ,33,49 In a later study in patients with VAP by Fagon
and coworkers,33 the overall attributable mortality for
VAP was 27% but increased to 43% when the cause
was P aeruginosa or Acinetobacter sp.
was
an

Cost

Several investigators have reported that nosocomial

pneumonia increases the duration of hospitalization
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twofold to threefold than for patients without pneumonia:37,49,52,56 In a more recent study of mechanically
ventilated patients, Fagon and coworkers33 found the
mean length of stay was 34 days for patients with VAP
compared to 21 days for matched controls subjects.
Although more specific data are needed, nosocomial
pneumonia appears to dramatically increase hospital
costs for survivors, which may translate into loss of
revenue for hospitals.57
Risk Factors

Several studies have been done of risk factors for

nosocomial pneumonia in different populations of pa
tients (Table 3).2,37,41,42,49"51,58"61 In general, risk fac
tors can be divided into host factors and underlying
disease, factors such as antibiotics and hospitalization
in an ICU that enhance colonization of the oropharynx
and stomach, factors that increase the risk of aspiration
of nosocomial pathogens into the lower respiratory
tract, and devices or equipment that interrupt natural
host defenses, many of which are summarized below.
Control measures and the Centers for Disease Control
(CDC) Hospital Infection Control Practices Advisory
Committee's (HICPAC) recommendations are shown
in Table 4.
Colonization and Aspiration as Risk Factors
Most cases of nosocomial pneumonia result from
aspiration of bacteria from the oropharynx or stomach
into the tracheobronchial tree (Fig 3). Approximately
45% of healthy subjects aspirate during sleep,62,63 and
aspiration is more frequent in patients with altered
consciousness, abnormal swallowing, depressed gag
reflexes, delayed gastric emptying, or decreased gas
trointestinal motility. Aspiration may be diminished by
maintaining ventilated patients in an semiupright po
sition, unless contraindicated.41,64,65
Early studies by Johanson et al66 demonstrated
Gram-negative bacillary colonization rates of 35% in
ill and 73% in critically ill patients. Pneu
moderately
monia occurred in 23% of the colonized patients
to 3.3% of the patients without coloniza
compared
tion. 7 Endotracheal intubation of the patient not only
compromises the natural barrier between the orophar
ynx and trachea, but also facilitates the entry of bacte
ria into the lung (Fig 4).26,68"74
Gastric colonization as a potential source of oropha
ryngeal and tracheal colonization in mechanically
ventilated patients was first suggested by Atherton and
White.75 Subsequent studies in ventilated patients, by
du Moulin et al76 indicated that levels of Gram-nega
tive bacilli in the normally sterile stomach may reach
100 million organisms/mL at a gastric pH=6. The
stomach is normally sterile because hydrochloric acid
has potent bactericidal activity.77 Increases in gastric
colonization may occur with advanced age, achlorhyContemporary Issues in Pulmonary Infections

Table 3.Risk Factors for Bacterial Nosocomial Pneumonia That Have Been Identified in Selected Studies*
Risk Factor

Ventilator-associated pneumonia (VAP)

Independent risk factors

Age ^60 years

COPD/PEEP/pulmonary disease
Coma/impaired consciousness
Therapeutic interventions^
Intracranial pressure monitor
Organ failure
Large volume gastric aspiration
Prior antibiotics
H2 blocker antacids
Gastric colonization and pH
Season: fall, winter

Ventilator circuit changes 24 vs 48 h

Reintubation
Mechanical ventilation >2 days

Tracheostomy

Supine head position

Ventilated and nonventilated patients

Independent risk factors

Age >60 years

APACHE II >16

Trauma/head injury
Impaired airway reflexes
Coma

Bronchoscopy

Nasogastric tube

Endotracheal intubation
Upper abdominal/thoracic surgery
Low serum albumin
Neuromuscular disease
Univariate risk factors for pneumonia
Age >60 years
Male sex

Smoking
Underlying disease (RF vs NF/UF)

SAPS >9
ASA class IV
FIo2 >.50
Prior care facility

Alcohol intake
Renal failure/dialysis
Intra-aortic balloon pump
COPD
Chemical paralysis

Airway instrumentation
Aspiration before intubation

Mechanical ventilation >2 days

No prior surgery
H2 blockers or antacids vs sucralfate

Coma

Head trauma
Cascade humidifier vs HME

Tracheostomy

Continuous enteral feeding

Prior antibiotics
Nosocomial maxillary sinusitis

Author and Reference

Torres34, Kollef41
Torres,34 Gaynes et al,175 Konrad et al61
Rello et al,18 Konrad et al61
Konrad et al61
Craven et al,50 Daschner et al86

Kollef41
Torres34
Kollef41

Craven et al,50

Gaynes et al174

Daschner et al86

Craven et al50
Craven et al50

Torres34

Torres,34 Gaynes et al,1/5 Konrad et al,61 Daschner et al86

Daschner86
Kollef41

Celis et al42
Chevret et al175
Chevret et al175
Chevret et al175
Chevret et al175

Joshi et al176
Celis et al,42 Joshi et al176 Cheadle et al111
Hanson et al178, Chevret et al175
Joshi et al,176, Celis et al42
Hanson et al17'
Hanson et al177

Fagon et al15

Konrad et al61
Konrad et al61

Torres,34 Fagon et al15

Chevret et al175
Konrad et al61
Chevret et al175

Kollef41
Torres34
Kollef41
Kollef41
Daschner et al86

Kollef41
Torres34
Daschner et al86

Gaynes et al,174 Langer et al,73 Kollef41

Torres34
Driks et al178, Prod'hom et al,27 Tryba,88 Kappstein et al179
Torres,34 Joshi et al176
Daschner et al86

Torres34

Torres,34 Daschner et al86

Jacobs et al180
Fagon et al15
Rouby et al95

Continued

Excludes risk factors for pneumonia due to L pneumophila which are described in the text. Abbreviations: H2=histamine type 2; APACHE=acute
physiologic score and chronic health evaluation; APS=acute physiologic score; SAPS=simplified acute physiologic score; HME=heat moisture ex
changer; RF=rapidly fatal; NF=nonfatal; UF=ultimately fatal.
f Interventions were markers of severe
underlying disease and included dopamine, dobutamine ^5 micrograms/min, barbiturate therapy for increased
intracranial pressure, continuous intravenous antiarrhythmic or antihypertensive therapy.61
*

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Table 3.Continued
Author and Reference

Risk Factor
Univariate risk factors for pneumonia
Type of intensive care unit
Repeat ICU admissions
APACHE II or APS score

Jarvis et al44
Kollef41
Kollef41
Kollef41

Emergency surgery
Nasotracheal tube
Nasogastric tube
Subglottic secretions

dria, various gastrointestinal diseases and malnutrition,

or treatment with antacids, or histamine type 2 (H2)
blockers.77"85 Retrograde movement of bacteria from

Rouby et al95

Celis et al,42 Rouby et al,95 Cheadle et al111

Mahul et al,98 Valles et al26

OROPHARYNGEAL^

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GASTRIC
COLONIZATION

COLONIZATION

ASPIRATION

antacids, H2 blockers, or sucralfate, even though none

of the agents currently used in the United States are
currently approved for this use by the Food and Drug
Administration.87 Several randomized studies, using a

6S

RESPIR ATORY|
THERAPY

INVASIVE
DEVICES

EQUIPMENT]

the stomach may increase the risk of oropharyngeal

and tracheal colonization, particularly if the patient is
in the supine position.41,64,65,76,86
Mechanically ventilated patients in critical care units
are often prescribed stress bleeding prophylaxis with

clinical diagnosis, have suggested that rates of VAP are

lower in persons given sucralfate com
significantly
to
and/or H2 blockers (Fig 5).27>87-89
antacids
pared
This may be related to the fact that, compared to ant
acids and H2 blockers, sucralfate does not have a ma
jor effect on gastric pH, but other mechanisms may
also explain these differences.86,90
Cross Infection and Colonization as Risk Factors
Cross colonization plays a major role in the spread
of nosocomial pathogens. Gram-negative bacilli are
and are often present in high concentra
ubiquitous
tions both in critically ill patients, in the hospital envi
ronment, and on the hands of hospital personnel.22,91
Proper handwashing, before and after patient contact,
is an effective means of removing transient bacteria.92
Because of the vagaries of handwashing among hospi
tal personnel, some have advocated the use of gloves
and gowns for contact with all patients, a practice
which has been associated with significantly decreased
rates of nosocomial infections in pediatric ICUs.47,93
Endotracheal Tube as a Risk Factor
Devices that circumvent host defenses or facilitate
the entry of bacteria into the lung are of great
concern 42,70-73,94-97 The presence of an endotracheal
tube impairs natural host defenses against infection
and increases the patient's risk of VAP.37,42,50 Leakage
around the cuff allows subglottic secretions pooled
above the cuff to enter the trachea (Fig 6). Mahul and
associates98 reported a decrease in the incidence of
VAP and a delay in the development of pneumonia
using manual intermittent aspiration of subglottic se
cretions. In a more recent study, Valles and cowork-

MEDICATIONS

HOST
FACTORS

NUMBERS OF BACTERIA
VIRULENCE

LUNG DEFENSES
BACTEREMIA

MECHANICAL
CELLULAR/HUMORAL

TRANSLOCATION,
?

PNEUMONIA
Figure 3. Summary ofrisk factors contributing to colonization and
infection of lower respiratory tract. Important risk factors include
the inoculum and virulence of infecting agents, response of
pulmonary host defenses in the lung. Reproduced from Craven et

ers26 reported that the use of continuous aspiration of

subglottic secretions (CASS) reduced the incidence of

episodes per 1,000 ventilator-days in

the control group to 19.9 episodes in the group
randomized to CASS (relative risk 1.98 (95% CI=1.033.82).26 The effect was most dramatic during the first
2 weeks ofintubation and was primarily associated with
a reduction of H influenzae and Gram-positive cocci

VAP from 39.6

SH
SH
SH
SAH
DRIKS KAPPSTEIN LAGGNER GARCIA

S H
S H
SAH
RYAN EDDLESTON PROD'HOM

of nosocomial pneumonia in
Summary of reported rates
randomized to stress bleeding
mechanicallywithventilated
patients
sucralfate (S) vs antacids (A), antacids and/or H2
prophylaxis
blockers
or H2 blockers alone
from Craven
Figure 4.

et

al.182

(AH),

(H). Reproduced

Contemporary Issues in Pulmonary Infections

Gastric Tube

Pharynx

Endotracheal
Tube

Endotracheal Tube
Gastric Tube

Esophagus
Larynx

Suction of

Subglottic

Figure 5. Example of an intubated patient with

continuous aspiration of subglottic secretions as re

coworkers.26 Removal of sub

ported secretions
by Valles and
decreases colonization of trachea
glottic
and risk of ventilator-associated pneumonia. Note
that the endotracheal tube is inserted through mouth
rather than nose and that the gastric tube is also in
serted through the mouth which reduces the risk of
nosocomial sinusitis and VAP. Reproduced from
Craven and

Trachea

Secretions

(CASS)

Subglottic Pooling
Aspiration Port for
Subglottic Secretions (CASS)

tomac

Endotracheal Tube Cuff

Steger.181
such as streptococci and S aureus. No differences were
noted in crude mortality, duration of ventilation, or
ICU stay. Because there appears to be little risk asso
ciated with the use of CASS, these current data suggest

this intervention has a favorable risk and cost-benefit

ratio.

Because the endotracheal tube is not routinely

changed, over 95% of the endotracheal tubes exam
ined by scanning electron microscopy had partial bac
terial colonization, and 84% were completely covered
in a biofilm or glueocalyx. Some investi
by bacteria
have
suggested that aggregates of bacteria in
gators
biofilm dislodged during suctioning may embolize to
the lung and may not be readily killed by antibiotics or

cleared by pulmonary host defenses.99100

effectively there
are no clinical studies to support this
However,
hypothesis.
Ventilator Tubing and Condensate as Risk Factors
The CDC/HICPAC guideline recommends that
mechanical ventilator breathing circuits be changed no
more frequently than every 48 h or as clinically indi
cated.101102 If a humidifier is used, the interval for
48 h is left to the discretion of the
change beyond
medical team.2
Ventilator tubing colonization and condensate may
occur rapidly after a tubing change in ventilator circuits
with humidifiers.103 Heated ventilator tubing will
reduce condensate formation. By compari
markedly
son, a heat moisture exchanger (HME) recycles ex
haled heat and moisture and eliminates circuit con

densate and the need for a humidifier. Although the

HME eliminates the problem of condensate, it may
add dead space to the circuit, increase circuit resistance
if it is clogged with secretions, and may not provide
sufficient humidity over time.2'104"110
Nasogastric Tube as Risk Factor
Patients may have a nasogastric tube placed to
manage gastric secretions, prevent gastric distention,

or

for nutritional support. The nasogastric tube is not

widely appreciated as a potential risk factor for pneu

monia but may increase the risk of nosocomial sinusi
tis, oropharyngeal colonization, reflux, and bacterial

migration.42'95'111
Nasotracheal intubation

and the presence of a

tube
are
nasogastric
important risk factors for nosoco
mial pneumonia and nosocomial sinusitis.42'46'95'111,112
However, the diagnosis of sinusitis is difficult to make
a paranasal computer tomo
clinically andandrequirestransnasal
scan
often
puncture to establish
graphic
the diagnosis and cause of sinusitis.95 The presence of
sinusitis as a risk factor for pneumonia has been
reported but is not widely appreciated.46 To date, there
have been few studies that adequately compared the
risk of sinusitis in patients with different methods of
intubation. In an important study by Rouby et al,95 the
presence of sinusitis was linked to the nasal placement
and duration of the endotracheal and gastric intuba
tion. Placement of the endotracheal and gastric tube

38%
53 NON INFECTIOUS
MAXILLARY SINUSITIS

43 INFECTIOUS

MAXILLARY SINUSITIS

Figure 6. Incidence of bronchopneumonia in the 96patients with

sinusitis on initial CT scan. The left pie chart
radiologic maxillary
represents 53 patients who were free of sinus infection after transnasal puncture and the right pie represents 43 patients with infec
tious maxillary sinusitis. Percentages within the pies represent the
proportion of patients with VAP (shaded area) compared to patients
without VAP (open area). The bar graph at right represents patients
with infectious maxillary sinusitis who secondarily developed a
with different
nosocomial

pneumonia

microorganisms (shaded

the identical microorganism (closed area) to the ones

identified in the sinus aspirate. Reproduced from Rouby et al.95

area)

or

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Table 4.Risk Factors and Appropriate Control Measures for Nosocomial Pneumonia
CDC/HICPAC

Control Measures

Risk Factors

Category*

Host

Age

Multiple or head trauma

Underlying disease.acute or chronic

Immunosuppression
M alnutri tion/obesi ty

Smoking

Alcohol abuse

Injection drug use

Depressed level of consciousness

Coma

Aspiration
Surgery
Trauma

Head/neck, chest/abdominal

Primary prevention

Kinetic beds/continuous lateral rotational therapy

Treat COPD.incentive spirometry-vaccines
Taper steroids cytotoxic other agents, GOSF for neutropenia

Weight control
Nicotine patches/counseling
Addiction counseling
Counseling.access to drug treatment
Judicious use of sedation
Reduce risk of aspiration
Continuous aspiration of subglottic secretions

NRf

Rotating kinetic beds, continuous lateral rotational therapy

Proper antibiotic prophylaxis
Proper position of the patient

Rapid ambulation

Pain control
Incentive spirometry

Medications
Antibiotics

Antacids/histamine-type blockers
Environmental
Seasonal
Water
Air

Cross infection
Patient to patient

Staff to patient

Devices/Equipment
Invasive

devices/equipment

Endotracheal tube/intubation

Nasogastric tube
Ventilator circuits

Tubing condensate
Inline nebulizers

Spirometers, O2 sensors and

hand-powered resuscitation bags

NS
NR
II
IA
NS
NS
NS
NS
NS
IR

Encourage coughing and deep-breathing/postoperatively

NR

IA
IA
IB
IB
II
IB

Judicious use of antibiotic prophylaxis/vaccines

Avoid routine selective decontamination of digestive tract

IA

If indicated, use sucralfate rather than antacids H2 blockers

II

Awareness of seasonal pathogens.education

Surveillance for L pneumophila infections
Use proper filters for Aspergillus in high-risk patients
Check air flow in hospital

NS
IA
IB
NS

Educate and train personnel in proper asepsis and isolation

IA

Feedback nosocomial infection surveillance data

NS
IA
IA
IA

techniques
Respiratory isolation of patients with possible respiratory infection
Proper handwashing
Appropriate use of gown and gloves

NRf

Expeditious removal of devices

Appropriate cleaning and sterilization
Use oral intubation; avoid nasotracheal tube
Keep cuff inflated; aspirate subglottic secretions before deflating cuff
Continuous aspiration of subglottic secretions (CASS)
Avoid self-extubation/reintubation
Maintain semiupright patient position

IB
IA
NS
IB

or for diluting tube

feeding
Change ventilator circuits with humidifier no more than every 48 h
No time limit for changing circuits >48 h
Drain/discard ventilator tubing condensate away from patient
Hygrosepric condenser-humidifiers or heat moisture exchangers
Disinfect between treatments
Replace between patients

NS*

Use orogastric tube

Remove as soon as possible
Use sterile rather than tap water to flush tube

Sterilize between patients

Clean/disinfect between patients or use filter to prevent

NRf
IA
IB
NS
IB
IA
NR
IB
NR
IB
IB
IA
IA

contamination

Tracheal suction catheters

Use

Tracheostomy care

Closed circuit tracheal suction catheter

Use sterile catheter for open system
Use aseptic technique when changing tubes

aseptic technique

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IA
NR
II
IB

Continued

Contemporary Issues in Pulmonary Infections

Table 4.Continued
CDC/HICPAC

Control Measures
Category*
NS*
Use oral gastric tube rather than nasogastric tube
Enteral feeding
IB
Remove tube as soon as possible
IB
Elevate head of bed 30 to 45 degrees if not contraindicated
IB
Routinely assess patient's intestinal motility and adjust rate
NR
Small or large bore gastric tubes
NR
Acidification of gastric feedings
IB
Check placement of tube
NR
Use of intermittent vs continuous enteral feedings
IB
Remove tube as soon as possible
experimental or epidemiologic studies.
*Category IA=Strongly recommended for all hospitals and strongly supported by well-designed
Category IB=Strongly recommended for all hospitals and viewed as effective by experts in the field and a consensus of HICPAC based on strong
rationale and suggestive evidence, even though definitive scientific studies may not have been done.
by suggestive clinical or epidemiologic studies,
Category 11=Suggested for implementation in many hospitals. Recommendations may be supported
a strong theoretical rationale or definitive studies applicable to some but not all hospitals. No recommendation (NR) unresolved issue is defined as
"practices for which insufficient or consensus regarding efficacy exists. From reference 2. NS=not specified in CDC/HICPAC guideline.
^SDD not recommended for routine use; CASS system not yet available in United States.
*We recommend use of oral gastric tube and advocate the use of sterile water to administer medications and dilute tube feedings.
Adapted from Craven and Steger.181
Risk Factors

decreased the incidence of infec

orally significantly
sinusitis
maxillary
(p<0.001) (Fig 6). Organisms
isolated from the maxillary sinus aspirates were most
P aeruginosa and Acinetobacter spp, S au
commonly
reus, and Candida albicans. In addition, VAP occurred
in the patients with
significantly more 67frequently
maxillary sinusitis, vs 43%, p=0.002). Of greatest
importance is that the risk of sinusitis and VAP can be
markedly reduced by the use of orotracheal and oro-

tious

gastric tubes.

Enteral Feeding as a Risk Factor

Poor nutritional status has been associated with
nosocomial pneumonia and led to the current trend of
early nutritional
support for critically ill patients.113
enteral
feeding may help maintain the epithelial
Early
barrier and prevent pneumonia caused by translocation or migration of bacteria across the gastrointestinal
barrier.114 Some investigators have postu
epithelial
lated that administration of enteral feedings with high
gastric
pH via the oral gastric tube may increase
colonization, volume, pressure, reflux, and pneumo
nia.115,116 Maintaining the patient in the upright posi
tion appears to reduce the frequency of gastric reflux.
In addition, care should be taken to prevent contam
ination of enteral feedings, and vigilance is needed for
their administration. Controversy remains over the use
of continuous vs intermittent feeding, the type and
bore of the feeding tube, and the optimal position of
the tube in the gastrointestinal tract.2,117'
Other Devices as Risk Factors
Detailed information on the risk of nosocomial
pneumonia and appropriate infection control preven

tion measures for other devices such as spirometer, the

oxygen analyzer, different tracheal suction catheters,
and nebulization equipment are discussed in this sup
plement and in detail elsewhere.2,119

Legionella pneumophila
Nosocomial pneumonia caused by L

pneumophila

may be endemic in hospitals with contaminated cool

ing towers or water supplies.2,120"128 Immunocompro

mised, critically ill patients, or those on corticosteroids

at highest risk of infection. Numerous nosocomial

outbreaks of Legionnaires' disease have been reported,
and rates of nosocomial pneumonia caused by this or
ganism range from 0 to 14% 2 Because culture, serology, and urinary antigen tests for Legionella are not
the incidence of Legionnaires'
routinelyis performed,underestimated.20
disease probably
Mortality rates
for nosocomial pneumonia due to L pneumophilia are
in the range of 40% and are nearly twofold higher than
are

infection.129,130
community-acquired
Inhalation of aerosols from showers, faucets, and
con
respiratory therapy equipment, and aspirationasofmeth
taminated potable water have been proposed
ods of transmission. In an earlier study of risk factors
for Legionella pneumonia by Blatt and coworkers,127
tube and antacid/H2 blockers were as
the

nasogastic

sociated risk factors. Recently, an interesting common

source outbreak of nosocomial VAP due to L pneu
type 6 was linked to the use of potable water
mophila
to administer medications and enteral feedings through
the nasogastric tube. The outbreak subsided by reduc
by
ing the levels of Legionella in the water supply andand
the use of sterile water to administer medications
enteral feedings through the nasogastric tube.
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Respiratory Viruses
Of the viruses causing nosocomial respiratory tract

infection, influenza and respiratory syncytial virus

(RSV) are most common.2,131"136 Most nosocomial
outbreaks follow community outbreaks.
Influenza pneumonia occurs most commonly in

persons who are elderly, immunosuppressed, or have

chronic underlying disease. Influenza usually occurs
annually in the winter months.2,134 Nosocomial out
breaks usually follow disease in the community, and
most outbreaks have occurred in nursing homes,
chronic disease facilities, ICUs, or pediatric wards.
Influenza is probably spread person-to-person by large
nuclei introduced into the respiratory tract of
droplet
a close contact, but transmission on hands or fomites
may occur.2,134 Infectivity is highest during the first 3
but may occur later in some patients.
days of illness
Diagnosis is often clinical and difficult to differentiate
from other respiratory viruses. Diagnosis maybe made
by culture of respiratory secretions and serologic con
version. Influenza may be prevented by vaccination if
the strain is in the vaccine and the host responds to
vaccination. Use of vaccine and prophylactic antiviral
agents such as amantadine may be effective for influ
enza A outbreaks in institutions.
RSV is most common during infancy and early
childhood. Disease is often mild but may be particu
severe in children who are immunocompromised
larly
or have chronic cardiac or pulmonary disease. RSV is

present in high concentrations in respiratory secretions

and can be transmitted by large respiratory droplet

close contact with infected persons or indirectly

during
contaminated hands or fomites. The conjunctiva
by
and nasal mucosa are potential portals of entry. Diag
nosis may be difficult to distinguish from other respi
ratory tract viruses. Culture of RSV remains the gold
standard, but antigen detection systems are rapid and
increasing in sensitivity and specificity. Once a labora
tory confirmed case of RSV is identified in the hospi
tal, subsequent cases are usually diagnosed presump
tively.
Several
of RSV have been identified in noso

types

comial outbreaks. Prevention efforts, as outlined in the

1994 CDC/HICPAC Guideline for Prevention of
Nosocomial Pneumonia, should be directed at con
taining the large reservoir of virus in infected patients
and transfer to and from hospital staff and visitors. A
wide spectrum of control measures have been tried
with varying degrees of success.2 For RSV, the em
phasis should be focused on contact isolation precau
tions, particularly gowning and gloving.47,137 However,
gloves must be changed between patients and precau
tions taken to avoid inoculation of eyes or noses.
Gowning also seems to prevent transmission from
contact with the environment. Special efforts, such as
private rooms or cohorting infected patients and staff,
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may be needed to prevent infection of

patients.

high-risk

Fungi

AlthoughratesAspergillus
pneumonia is uncommon,
are
mortality
high. Aspergillus spp, which are
in
found
soil, water, and decaying vegeta
commonly
tion, have been cultured from unfiltered air in the
ventilation systems and may be in par
hospital, and concentrations
high
ticularly
during hospital construc
tion and renovation.138"142 Nosocomial respiratory in
fection due to Aspergillus usually occurs in immuno
compromised patients, particularly those
undergoing
or with AIDS.
chemotherapy, organ transplantation,
A flavus are the most
Aspergillusisolated
fumigatus andfrom
frequently
species
patients. Diagnosis is
often difficult and usually requires bronchoscopy with
BAL or biopsy to discriminate between airway coloni
zation and tissue invasion.
A single case of nosocomial Aspergillus pneumonia
should raise suspicion and initiate a careful investiga
tion of other possible cases. Information for the eval
uation of hospital airflow systems is contained in the
1994 CDC/HICPAC Guideline for Prevention of
Nosocomial Pneumonia.2 Clearly, efforts should be
taken to avoid exposure of high-risk patients to envi
ronmental reservoirs of the organism. If possible, the
isolates should be saved for molecular typing to corre
late the case to a specific environmental source.
Candida albicans may become a pathogen for
nosocomial pneumonia in immunosuppressed or crit
This is due to the use of
ically ill patients.143"146
broad spectrum antibiotics to treat
chemotherapy,
bacterial infections, and cross contamination between
patients. Molecular typing studies have helped estab
lish the mode of nosocomial transmission and to iden
both patient and hospital reservoirs of the orga
tify
nism.143
HIV Disease and Emerging Pathogens
Over one million persons in the United States are
infected with HIV type 1 (HIV) and more than 400,000
cases of AIDS have been reported to the CDC as of
January 1995.147 As the result, there has been a steady
increase in numbers of HIV-infected patients cared for
in hospitals, outpatient clinics, and long-term health

facilities. Because AIDS patients appear to have

greater risk of nosocomial infection, the use of inva
sive devices, prior exposure to antibiotics, and hospital
visits should be limited.148,149
Bacterial infections are prevalent in HIV-infected
persons, and the lung is a common site of infection.
Nichols and coworkers,150 reported bacterial infection
was present in 83% of 46 autopsied AIDS patients and
contributed to the death in 36% of these cases. Pneu
monia was the most common bacterial infection,
care
a

Contemporary Issues in Pulmonary Infections

occurring in more than 50% of the patients. Niedt and

Schinella151 found bacterial infection in more than
50% of 56 autopsies, and pneumonia was again the
most common site of infection. S aureus and P aeru
ginosa were the most common organisms isolated.
Although most of the data on nosocomial pneumo
nia in HIV-infected patients are focused on the tradi
tional pathogens such as P aeruginosa and S aureus,
there is concern that many of the traditional "com
munity-acquired" respiratory pathogens, such as pneumococcus, H influenzae, M tuberculosis, and even
Pneumocystis carinii pneumonia (PCP) may be ac
and transmitted in the hospital.
quired
HIV-infected
have rates of
persons

pneumococcal

pneumonia that are estimated to be increased 5- to

15-fold over HIV-seronegative persons.152"154 Re

cently,
Blumberg and Rimland155 described apparent
nosocomial transmission a

of type 6A, MDR-strain of

between
two
AIDS patients that were
pneumococcus
three
rooms
hospitalized
apart. The isolates were
to
that
had
unique
hospital, identical serotype, and
unusual antibiogram resistance patterns. Of note is that
the second patient probably developed pneumococcal
bacteremia and pneumonia 20 days after exposure and
following his discharge from the hospital. Suggestion of
nosocomial transmission has also been reported for
outbreaks of penicillin-resistant pneumococci in Spain
and South Africa.156,157 These data raise concerns
about nosocomial transmission of respiratory patho
gens and underscore the potential misclassification of
hospital-acquired infections based on our current def

inition.

The risk for H influenzae pneumonia is estimated to

be 79 per 100,000 in persons with AIDS compared to
2 per 100,000 in healthy adults.158,159 Approximately
33% of the cases are caused by type b organisms; the
remainder are nontypeable strains. Although there is a
vaccine available for protection
protein-polysaccharide
against type b disease, like pneumococcal vaccine, the
immune response of persons with AIDS is impaired.160
Published data indicate that rates of H influenzae,
type b disease are higher in household contacts and
that person-to person spread is important in house
holds and in health-care facilities.161"163 Thus, proper
respiratory isolation and use of infection control tech
niques may be crucial in preventing the nosocomial
spread of bacterial respiratory pathogens.
Mycobacterium tuberculosis (MTB)
The association between HIV infection and the ris
ing rate of infection due to MTB in the United States
has been well documented with pulmonary tubercu
losis occurring in 70 to 93% of MTB cases in HIV-in
fected patients.164,165 Of note is that AIDS patients
may have a negative tuberculin skin test and an atyp
ical clinical presentation. Two recent epidemiologic

using analysis of restriction-fragment-length

(RFLP) have suggested that recently
polymorphisms
transmitted MTB accounted for two thirds of the ac
tive MTB cases in HIV-infected individuals, and that
HIV infection was an independent risk factor for hav
ing a "cluster isolate."166,17
studies

Nosocomial outbreaks of MTB involving HIV-in

fected persons have been characterized by attack rates
that range from 5 to 44%, rapid progression to active
disease, evidence of significant spread in health-care
settings, and high mortality.7,168 Several nosocomial
outbreaks have been reported, many of which have
strong epidemiologic data supported by a molecular
of the outbreak strains.
analysis
Factors that contributed to the outbreaks include an
increasing number of HIV-infected patients exposed to
MTB, delays in proper isolation, diagnosis, treatment,
and drug susceptibility results. In addition, inadequate
ventilation, lack of isolation rooms with positive air
pressure, and inadequate precautions for cough-in
ducing procedures such as administration of aero
solized pentamidine and bronchoscopy have contrib
uted to transmission.
In response to the growing number of MTB out
breaks, the CDC has published a set of guidelines for
preventing MTB transmission in health-care settings
which will be updated in 1995.169 These guidelines
stress early identification of active disease, prompt
isolation, and expeditious initiation of effective ther
apy. In addition, routine skin testing for MTB exposure
among health-care workers and when appropriate, a
contact investigation coupled with appropriate preventative therapy is recommended.
P carinii Pneumonia
Current epidemiologic and animal studies

suggest

that airborne droplets are the most likely source of PCP

transmission. Clusters or hospital outbreaks of PCP in
the United States were reported in immunosuppressed
children beginning in 1968.170 The use of sputum in
duction, bronchoscopy, or aerosolized pentamidine
treatment in HIV-infected patients may increase the
risk of nosocomial transmission of PCP. Hoover and
coworkers171 found temporal and geographic relation
ships suggesting person-to-person spread of P carinii
in HIV-infected men, compared to HIV-seronegative
control subjects. Also, Haron and coworkers1 re
increased rates of PCP among cancer patients
ported
in their institution from 1980 to 1987, which parallelled
the increasing numbers of cases of AIDS admitted to
their institution. Although no specific epidemiologic
routes of transmission could be determined, the AIDS
clinic and leukemia outpatient clinics were contiguous,
and the two patient populations mingled freely. Chave
and coworkers173 identified PCP in 5 of 144 renal

transplant recipients over a 22-month period. All five

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11S

patients attended the same outpatient facility where

shared waiting and treatment rooms and had en
they
counters with AIDS patients who later developed PCP.
these data on nosocomial transmission are
Although
not conclusive, they are suggestive and suggest that
precautions should be instituted to prevent the noso
comial spread of P carinii among immunosuppressed
patients.
Conclusions

1980s, significant strides were made in our

understanding of nosocomial pneumonia, but greater

1
2

ities.

ACKNOWLEDGMENTS: The authors thank Maria

Tetzaguic,
David Allen, and Sebastian Morel for assistance in the preparation
of the manuscript.
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pneumonia: state of the art and perspectives for the 1990's. Am

J Med 1991; 91(suppl 3B):44S-53S
Tablan OC, Anderson LJ, Arden NH, et al. Guideline for
prevention of nosocomial pneumonia: Part I. Issues on prevention
of nosocomial pneumonia, 1994. Infect Control Hosp Epidemiol

1994; 15:588-625
TC, White JW, Jarvis WR, et al. Nosocomial infection
surveillance, 1984. M.MWR 1986; 35:17SS-29SS
4 Craven DE, Steger KA, Duncan RA. Prevention and control of
nosocomial pneumonia. In: Wenzel RP, ed. Prevention and con
3 Horan

trol of nosocomial infections. 2nd ed. Baltimore: Williams and

In the

effort is needed during the remainder of the 1990s.

Continued national surveillance data with more ap
propriate definitions relevant to the increase in AIDS
and other immunosuppressed patients, decreasing
of hospital stay, and applicability to outpatient
length
and chronic care settings are needed to monitor etio
logic agents and the emerging pathogens. In addition,
the use of molecular epidemiologic techniques should
define outbreaks, mechanisms for colonization,
help
and the interactions between nosocomial pathogens
and pulmonary defenses.
Diagnosis of nosocomial pneumonia remains a ma
jor problem for clinicians and hospital epidemiologists.
Research is needed to improve the diagnosis of noso
comial pneumonia with noninvasive techniques.
Guidelines are needed for the cost-effective use of
with BAL or PSB or quantitative en
bronchoscopy
dotracheal aspirates in the diagnosis of VAP. There is
a need for improved infection control strategies, such
as maintaining the patient in a semi-upright position,
nasotracheal tube with oral intubation, and
replacing
oral
using gastric tubes rather than nasogastric tubes.
In addition, the use of continuous aspiration of sub
glottic secretions may reduce the rate of VAP per 1,000
ventilator days. Well-designed trials to analyze risk,
benefit, and cost of these devices should be a prereq
uisite to their routine use. Optimal management of
tube feeding, coupled with the effective use of nutri
tional support deserve further investigation. In addi
tion, better studies are needed to define the appropri
ate use and duration of antibiotic therapy, with or
without immunotherapy, for the prevention and treat
ment of nosocomial pneumonia. Health-care workers
are encouraged to use effective respiratory precautions
until the patients respiratory diagnosis is clear in order
to prevent transmission of pneumococci, H influenzae,
MTB, respiratory viruses, and PCP on the inpatient
service, outpatient clinics, and long-term health facil

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