Impact of BAL on the diagnosis and treatment of nosocomial pneumonia in ICU patients.
ABSTRACT Nosocomial pneumonia and ventilator-associated pneumonia are currently the second leading cause of nosocomial infections and account for approximately 10-15% of all hospital-acquired infections. Crude mortality rates range from 24% to 76% depending on the population and clinical setting studied. During the last ten years, several diagnostic methods have been developed to microbiologically confirm the clinical diagnosis, especially in mechanically ventilated patients. This article seeks to clarify the issues surrounding the use of invasive fiberoptic bronchoscopic techniques in the diagnosis and treatment of nosocomial pneumonia.
- SourceAvailable from: 22.214.171.124[show abstract] [hide abstract]
ABSTRACT: To describe the epidemiology of nosocomial infections in pediatric intensive care units (ICUs) in the United States. Patient and ICU characteristics in pediatric ICUs suggest the pattern of nosocomial infections experienced may differ from that seen in adult ICUs. Data were collected between January 1992 and December 1997 from 61 pediatric ICUs in the United States using the standard surveillance protocols and nosocomial infection site definitions of the National Nosocomial Infections Surveillance System's ICU surveillance component. Data on 110 709 patients with 6290 nosocomial infections were analyzed. Primary bloodstream infections (28%), pneumonia (21%), and urinary tract infections (15%) were most frequent and were almost always associated with use of an invasive device. Primary bloodstream infections and surgical site infections were reported more frequently in infants aged 2 months or less as compared with older children. Urinary tract infections were reported more frequently in children >5 years old compared with younger children. Coagulase-negative staphylococci (38%) were the most common bloodstream isolates, and aerobic Gram-negative bacilli were reported in 25% of primary bloodstream infections. Pseudomonas aeruginosa (22%) was the most common species reported from pneumonia and Escherichia coli (19%), from urinary tract infections. Enterobacter spp. were isolated with increasing frequency from pneumonia and were the most common Gram-negative isolates from bloodstream infections. Device-associated infection rates for bloodstream infections, pneumonia, and urinary tract infections did not correlate with length of stay, the number of hospital beds, or season. In pediatric ICUs, bloodstream infections were the most common nosocomial infection. The distribution of infection sites and pathogens differed with age and from that reported from adult ICUs. Device-associated infection rates were the best rates currently available for comparisons between units, because they were not associated with length of stay, the number of beds in the hospital, or season.PEDIATRICS 05/1999; 103(4):e39. · 4.47 Impact Factor
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ABSTRACT: Cases of pneumonia during the first 21/2 years of a respiratory-surgical intensive care unit (R-SICU) were analyzed. One hundred fifty-eight episodes of pneumonia were identified in 153 patients. Patients without pneumonia had a mortality of 3.8%. Patients admitted with or acquiring Gram-positive pneumonia did not have increased mortality. Patients who had Gram-negative pneumonias without involvement by Pseudomonas aeruginosa had a mortality of 33%. Isolation of Pseudomonas from respiratory cultures obtained from patients with pneumonia was associated with a mortality of 70%. Overall mortality of all patients admitted during the 30-month period was 13%. Eastablished Gram-negative Bacillus pneumonias are common, dangerous, and often not effectively treated. Environmental sources of Gram-negative pathogens should be reduced. Prophylactic regimens to prevent colonization of the respiratory tract may be helpful.Archives of Internal Medicine 08/1974; 134(1):106-11. · 11.46 Impact Factor
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ABSTRACT: Epidemiologic studies of nosocomial bacterial pneumonia in patients requiring mechanical ventilation have been limited because of the poor reliability of diagnosis procedures in this setting. To determine prognostic and descriptive factors of ventilator-associated (V-A) pneumonia, we prospectively studied 567 patients who had been receiving mechanical ventilation for more than 3 days in our unit. Fiberoptic bronchoscopy using a protected specimen brush (PSB) was performed on each patient suspected of having pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions. The diagnosis of V-A pneumonia was retained only if PSB specimens yielded greater than 10(3) cfu/ml of at least one microorganism, unless this result was established to be a false positive result on follow-up. V-A pneumonia developed in 49 patients for a total of 52 episodes (9%). The actuarial risk of V-A pneumonia was 6.5% at 10 days, 19% at 20 days, and 28% at 30 days of ventilation. Patients with pneumonia were significantly older (65 versus 57 yr of age, p less than 0.01) and more frequently had severe underlying illnesses (24 versus 10%, p less than 0.01) than did patients without pneumonia. A total of 84 microorganisms (51 gram-negative and 33 gram-positive) were isolated in significant concentrations from PSB specimens. Pseudomonas aeruginosa and Staphylococcus aureus were involved in 31 and 33% of these pneumonias, respectively. Forty percent of all specimens yielded a polymicrobial flora with more than one potential pathogen.(ABSTRACT TRUNCATED AT 250 WORDS)The American review of respiratory disease 05/1989; 139(4):877-84. · 10.19 Impact Factor
Monaldi Arch Chest Dis
2001; 56: 6, 521–526
Impact of BAL on the diagnosis
and treatment of nosocomial
pneumonia in ICU patients
R. Ferrer*, M. Ioanas, C. Agustí, A. Torres
Nosocomial pneumonia and ventilator-associ-
ated pneumonia (VAP, i.e. nosocomial pneumonia
after 48 hours of mechanical ventilation) are cur-
rently the second leading cause of nosocomial in-
fections and account for approximately 10-15% of
all hospital-acquired infections. The incidence of
nosocomial pneumonia is increased for all patients
in intensive care units (ICU), where respiratory in-
fections have been reported to be the most frequent
type of nosocomial infection .
Crude mortality rates range from 24% to 76%
depending on the population and clinical setting
studied [5–9]. Morbidity is also enhanced in pa-
tients with nosocomial pneumonia. Initial reports
found that pneumonia extended the ICU stay
threefold [10, 11]. This figure was later corrobo-
rated by others: Leu et al. reported 9.2 days of ad-
ditional hospital stay and Fagon and co-workers
calculated the median length of stay in the ICU for
patients that developed VAP as 21 days, versus a
median of 15 days for control patients . Com-
parable figures were also reported for trauma pa-
tients with VAP .
During the last ten years, several diagnostic
methods have been developed to microbiologi-
cally confirm the clinical diagnosis, especially in
mechanically ventilated patients . These
methods require the use of bacterial quantitative
cultures and for each method a specific bacterial
threshold is accepted for the confirmation of a
pulmonary infection . However, despite the
enormous amount of literature regarding this top-
ic, there is still an open debate about the necessi-
ty for invasive fiberoptic bronchoscopic tech-
niques [17, 18].
Criteria for clinical suspicion of VAP
Clinical observations, laboratory results and
chest radiographs are of limited value in diagnos-
ing VAP, so great effort has been made to establish
independent microbiological criteria. However,
these efforts have so far not succeeded. Despite its
limitations clinical assessment is the starting point
for diagnosing VAP and alternative strategies must
be interpreted with regard to their ability to de-
crease the rate of false-positive clinical judgments.
The clinical diagnosis is based on the presence
of new and persistent pulmonary infiltrates, fever
>38.3ºC, leukocytosis and purulent secretions
. Although these parameters are fairly straight-
forward in non-ventilated patients they frequently
present false-positive and false-negative results in
patients on mechanical ventilation.
We performed an immediate postmortem his-
tological analysis of multiple pulmonary biopsies
in order to assess the diagnostic value of the clini-
cal criteria proposed by JOHANSON et al.  in the
diagnosis of VAP. We found that the presence of
infiltrates on the chest radiograph and two of three
clinical criteria (leukocytosis, purulent secretions
and fever) have a sensitivity of 69% and a speci-
ficity of 75% . An effort to improve the diag-
nostic yield of clinical parameters was made by
Pugin et al. who designed a score combining clin-
ical, physiological and microbiological parameters
Keywords: Nosocomial pneumonia, bronchoscopy, BAL.
*Servei de Medicina Intensiva, Hospital Parc Tauli, Sabadell, and Servei de Pneumologia, Institut Clinic de Pneumologia
i Cirugia Toràcica. Hospital Clinic i Provincial, Barcelona, Spain.
Correspondence: Dr. Antoni Torres; Hospital Clinic i Provincial; Servei de Pneumologia i Al.lèrgia Respiratoria; Villarroel, 170;
E-08036 Barcelona; e-mail: email@example.com
ABSTRACT: Impact of BAL on the diagnosis and treat-
ment of nosocomial pneumonia in ICU patients. R. Ferrer,
M. Ioanas, C. Agustí, A. Torres.
Nosocomial pneumonia and ventilator-associated
pneumonia are currently the second leading cause of noso-
comial infections and account for approximately 10-15%
of all hospital-acquired infections. Crude mortality rates
range from 24% to 76% depending on the population and
clinical setting studied. During the last ten years, several
diagnostic methods have been developed to microbiologi-
cally confirm the clinical diagnosis, especially in mechani-
cally ventilated patients. This article seeks to clarify the is-
sues surrounding the use of invasive fiberoptic broncho-
scopic techniques in the diagnosis and treatment of noso-
Monaldi Arch Chest Dis 2001; 56: 6, 521–526.
called clinical pulmonary infection score (CPIS)
. However in our postmortem study, CPIS was
not superior to clinical criteria in the diagnosis of
VAP . A major reason for false-negative re-
sults of clinical parameters are the quality defi-
ciencies of portable chest X-ray and the fact that
the histological pattern of VAP (diffuse bronchop-
neumonia) is not easily detected in the initial peri-
ods by portable chest-X ray . False-positive re-
sults are explained by the frequent presence of
other pulmonary lesions such as alveolar hemor-
rhage, or diffuse alveolar damage .
Several diagnostic methods have been devel-
oped to microbiologically confirm the clinical di-
agnosis. It is important to confirm the clinical sus-
picion criteria and to provide reliable information
on the causative agent and its susceptibility be-
cause inadequate antibiotic treatment is related to
a poor prognosis and, in addition, antibiotic
overtreatment may select more virulent organisms
such as Pseudomonas aeruginosa or Acinetobacter
Bronchoalveolar lavage and other
bronchoscopic diagnostic methods
The introduction of the flexible fiberoptic
bronchoscope in the late 1960s resulted in a safe
and accurate technique to directly access lower air-
ways, of great use for the diagnosis of various pul-
monary lesions. Its usefulness has been extended
to the collection of lower airway secretions from
the site of presumed infection. An additional ben-
efit is the by-passing of the oropharynx which is
usually colonized by potential pulmonary
pathogens especially in hospitalized patients, lead-
ing to misinterpretation of the respiratory samples.
The most commonly used bronchoscopic methods
are bronchoalveolar lavage (BAL) and protected
specimen brush (PSB) .
BAL is performed by advancing the broncho-
scope distally into a subsegmental bronchus (gener-
ally a third- or fourth-generation bronchus) until the
airway is occluded proximally. The next step is the
instillation of 20 to 50 mL aliquots of sterile saline
into the lung periphery, followed by gentle aspira-
tion. As yet, there is no consensus about the total
volume to be instilled, but it is believed that at least
100 mL are required to retrieve secretions from the
periphery of the subsegment . The sampling
area is selected based on the location of the infiltrate
on chest x-ray or by direct visualization of a sub-
segment containing purulent secretions.
Other methods using protected systems have
been designed to avoid contamination of the re-
trieved BAL fluid, and hence are more expensive
. Blind BAL has been advocated in the form of
conventional methods , protected catheters us-
ing mini-BAL procedures , Swan-Ganz
catheters or more recently protected catheters that
can be directed to one or other side of the lung
. Overall, these methods have a similar accu-
racy, when protected, to the guided methods.
The alternative bronchoscopic method for di-
agnosis is PSB, which involves positioning the
bronchoscope next to the orifice of the sampling
area and advancing the PSB catheter 3 cm out of
the fiberoptic bronchoscope to avoid collection of
pooled secretions on the catheter tip. An inner can-
nula is protruded to eject a distal carbon wax plug
into the airway, and the catheter is advanced to the
desired subsegment. If purulent secretions are vi-
sualized, the brush is rotated there. This procedure
is necessary to avoid contamination of the brush
with microorganisms from the upper respiratory
BAL has some advantages with respect to
PSB, namely it allows a bigger area of sampling of
the lung and the possibility to determine levels of
cytokines and other parameters of the inflammato-
ry response. However, BAL is not without risk.
There are two types of risk: those inherent to the
use of the fiberoptic bronchoscope and those in-
herent to the instillation of fluid during bron-
choscopy. The most important and most common
consequences involve blood-gas exchange with
possible significant impairment in oxygenation
. Alterations in blod-gas exchange depend on
the type of lavage used (conventional BAL or pro-
tected BAL) and the amount of liquid instilled,
which ranges from 50 mL in mini-BAL to 150 mL
in conventional BAL. A sepsis-like syndrome has
been described after BAL in VAP patients. This re-
sponse is characterized by fever and by a decrease
in mean arterial pressure and arterial oxygenation,
and it seems related to the level of endotoxins in
the BAL fluid . The decrease of arterial oxy-
genation is independent of the volume of BAL
used and seems to be related to the alveolar bacte-
rial burden .
Non-invasive vs. bronchoscopic procedures
for microbiological diagnosis of VAP
There is still an open debate about the necessi-
ty for invasive fiberoptic bronchoscopic tech-
niques  in the management of nosocomial
pneumonia. Some authors propose that the use of
quantitative cultures of endotracheal aspirate could
be an equally correct and less invasive approach to
manage these patients. In patients with suspected
VAP, a variety of diagnostic tools have been eval-
uated with conflicting results [35–38]. These stud-
ies provided several general insights, although ref-
erences and thresholds for the calculation of diag-
nostic indices varied considerably. Firstly, PSB
and BAL had generally comparable diagnostic
yields; secondly, tracheobronchial aspirates had
comparable yields to PSB and BAL, with a ten-
dency towards a lower specificity; thirdly, all tools
exhibited a rate of false-negatives and false-posi-
tives ranging from 10-30%. A study focusing on
the variability of PSB demonstrated that the quali-
tative repeatability was 100%, whilst in 59% of the
patients the quantitative results varied more than
tenfold . Based on these studies, several inves-
tigations were performed using post-mortem his-
tology or lung culture as an independent reference
or gold standard [32, 40–44]. Despite several im-
portant methodological limitations these studies
R. FERRER ET AL.
revealed important clues as to the relationships be-
tween histology, microbiology and the diagnosis
of VAP, namely: a) that there is a limited correla-
tion between histology and bacterial load in the
cultures of lung specimens; b) that there is a sur-
prisingly high rate (10-50%) of false-negatives and
false-positives regardless of the technique used;
and c) that non-invasive and invasive diagnostic
tools have a comparable yield. Reasons for false-
negative findings included sampling errors, an-
timicrobial pretreatment and the presence of stage-
specific bacterial loads during the evolution of
pneumonia (developing as well as resolving pneu-
monia). Conversely, false-positives were attribut-
able to contamination of the samples and bronchi-
olitis or bronchitis, particularly in patients with
structural lung disease.
Three randomized studies have been published
evaluating the influence of diagnostic techniques
(invasive vs. non-invasive) on outcome, two from
Spain [45, 46] and one from France .
SANCHEZ-NIETO et al. compared a strategy based
on quantitative endotracheal aspirate with another
strategy based on quantitative cultures of BAL and
PSB and found no difference in outcome measures
such as mortality, cost, duration of hospitalization,
ICU stay and intubation . SOLE-VIOLAN et al.
compared a strategy based on quantitative cultures
of bronchoscopic and non-bronchoscopic tech-
niques with a strategy based on clinical judgment
plus non-quantitative cultures of tracheal aspirate,
with the same results . In contrast, the multi-
center French study found a bronchoscopic strate-
gy including quantitative cultures of PSB and/or
BAL to be superior to a clinical strategy using
qualitative tracheobronchial aspirates in terms of
14-day mortality, morbidity and use of antimicro-
bial treatment. Each study had limitations; howev-
er, the results of the French study, in particular,
raised the following concerns: firstly, the clinical
strategy did not necessarily reflect routine prac-
tice; secondly, it is not clear from the data how the
invasive strategy accounted for the better outcome;
thirdly, the clinical group had a significantly higher
rate of inadequate antimicrobial treatment [48, 49].
In the light of these data, non-invasive and in-
vasive bronchoscopic tools have comparable diag-
nostic yields and share similar methodological
Analysis of BAL samples
Analysis of the respiratory sample consists basi-
cally in microscopic evaluation and quantitative cul-
ture. Promising methods of rapid detection such as
polymerase chain reaction (PCR) need further stud-
ies to confirm their benefits in the diagnosis of VAP.
The microscopic analysis of the respiratory
1. Evaluation of the alveolar cell population (cell
count and differential). Several studies have
shown a significant increase in total neu-
trophilic count in the respiratory samples col-
lected by BAL and PSB in patients with VAP.
The mean percentage of neutrophils varies be-
tween 77 and 82% in BAL [21, 30, 50]. These
findings are consistent with a level of colony
forming units suggestive of pneumonia. The
percentage of epithelial cells (more than 1% of
squamous epithelial cells in the centrifuged
specimen) is considered to be a good predictor
of significant contamination with oropharyn-
geal flora of the BAL and PSB samples .
2. Calculation of the percentage of cells (neu-
trophils) containing intracellular organisms
(ICO) detected in BAL samples. Recent stud-
ies suggest that ICO could be useful for an ear-
ly diagnosis of pneumonia and the accepted
threshold value of infected cells is around 5%;
however, the sensitivity of the test varies great-
ly between 37% and 100% [21, 52, 53].
3. Stain for the recognition of organisms: Gram,
acid-fast (for mycobacteria), potassium hy-
droxide (for fungi). There is a good correlation
between the findings on the Gram stain of
BAL/PSB sample and the results of quantita-
tive cultures [21, 36].
4. Assessment of the presence of cytokines [tu-
mor necrosis factor (TNF)-α, interleukin (IL)-
1β, IL-6, IL-8]. Cytokines appear to be a
promising tool for differentiation of severe
sepsis, adult respiratory distress syndrome
(ARDS) and pneumonia [54–56].
The quantitative culture of the respiratory sam-
ple represents an important means for distinguish-
ing between colonisation and infection, based on
assessment of the concentration of organisms pre-
sent in the respiratory samples. However, the con-
centration of organisms necessary to cause pneu-
monia can vary in relation to the virulence of the
bacteria and the competence of host defences.
The respiratory sample collected by any
method and processed as described above is inoc-
ulated routinely into blood agar, chocolate agar,
centers for disease control and prevention (CDC)
agar, buffered charcoal yeast extract agar and
Sabouraud medium. Culture plates are incubated
at 37ºC under adequate aerobic and anaerobic
conditions and evaluated at 24 and 48 hours. The
results are expressed in colony forming units
(cfu). The threshold for BAL sample is 104cfu/ml
and 103cfu/ml for PSB. A cfu below threshold in
patients with clinical features of pneumonia
should not prohibit antibiotic treatment since it
could be an early phase of the infection. Suscepti-
bility tests are recommended routinely, if possible
by determination of minimal inhibitory concentra-
Polymerase chain reaction (PCR)
PCR is a rapid technique for detecting organ-
isms in the respiratory samples collected by BAL,
allowing an accurate bacteriological diagnosis in
BAL IN ICU NOSOCOMIAL PNEUMONIA
less than 7 hours . However, conventional
methods are preferred to it for several reasons:
PCR is expensive, time-consuming and needs
In summary, the current indications for BAL in
nosocomial pneumonia are:
1) Initial diagnosis: Microbiological confirma-
tion of clinical suspicion criteria of pneumonia
is needed in order to provide reliable informa-
tion on the causative agent and its susceptibil-
ity for guiding the right treatment and for pre-
venting the selective pressure of some antibi-
otics. BAL has a good sensitivity and speci-
ficity to determine the etiology of nosocomial
pneumonia and some studies conclude that
BAL may help to reduce antibiotic use in VAP.
However, in the light of current data, quantita-
tive cultures of tracheal aspirates in intubated
patients have a comparable diagnostic yield.
2) Treatment failure, i.e. absence of improvement
or clinical deterioration during antibiotic thera-
py, presents a dilemma to physicians. The im-
pact of BAL in the management of non-re-
sponding pneumonia has been evaluated in one
prospective study: 93% of patients were under
antibiotic treatment and BAL resulted positive in
73% of patients, with Acinetobacter baumanii,
Pseudomonas aeruginosa and MRSA being the
most common microorganisms. This result sug-
gest that BAL may be a sensitive diagnostic
method for treatment failures of pneumonia,
even if performed under antibiotic treatment.
3) BAL has been established as a reliable tech-
nique for the diagnosis of pulmonary infiltrates
in the immunosuppressed host, specifically for
detecting opportunistic infectious agents such
as P. carinii and cytomegalovirus and also for
bacteria . Moreover, BAL provides enough
material to diagnose alternative non-infectious
etiologies such as alveolar hemorrhage or alve-
olar proteinosis. In a recent study by our group
non-invasive and bronchoscopic diagnostic
techniques were applied in patients with differ-
ent immunocompromised conditions . The
bronchoscopic techniques led to the diagnosis
of pulmonary infiltrates in 59% of the cases in
which they were used, increasing the diagnos-
tic yield of pulmonary infiltrates and causing
changes in the empirical treatment in the ma-
jority of the patients. The main infectious eti-
ologies were Aspergillus fumigatus, Staphylo-
coccus aureus and Pseudomonas aeruginosa.
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BAL IN ICU NOSOCOMIAL PNEUMONIA