Diagnosis of Ventilator-associated Pneumonia by BacteriologicAnalysis of Bronchoscopic and Nonbronchoscopic "Blind"Bronchoalveolar Lavage Fluid1

,2

JEROME PUGIN, RAYMOND AUCKENTHALER, NABIL Mill, JEAN-PAUL JANSSENS,~ DANIEL LEW, and PETER M. SUTER

SUMMARY Substantial efforts have been devoted to improving the means for early and accuratediagnosis of ventilator-associated (VA)pneumonia in intensive care unit (leU) patients because ofIts high incidence and mortality. A good diagnostic yield has been reported from quantitative cul­tures of bronchoalveolar lavage (BAL) fluid or aprotected specimen brush, both obtained by flberop­tic bronchoscopy. As bronchoscopy requires specific skills and is costly, we evaluated a simplermethod to obtain BAL fluid, that Is, by a catheter Introduced blindly into the bronchial tree. Quantita­tive cultures from bronchoscoplcally sampled BAL (B-BAL) and blindly nonbronchoscopically col­lected BAL (NB-BAL) were assessed for sensitivity, specificity, and predictive value for the diagnosisof VApneumonia. A total of 40 pairs of samples were examined in 28 patients requiring prolongedmechanical ventilation and presenting a high risk of developing pneumonia. For comparison withbacteriologic data we defined a clinical score for pneumonia ranging from zero to 12 using the fol­lowing variables: body temperature, leukocyte count, volume and character of tracheal seerettens,arterial oxygenation, chest X-ray,Gram stain, and culture of tracheal aspirate. Toquantify the bacte­ria In BAL the bacterial Index (BI) was used, defined as the sum of the logarithm of the numberof bacteria cultured per milliliter of BAL fluid. A good correlation between clinical score and quan­titative bacteriology was observed (r = 0.84 for B-BAL and 0.76 for NB-BAL; p < 0.0001). Similarto studies in baboons, patients with pulmonary infection could be distinguished by a BI ~ 5 witha sensitivity of 93% and a specificity of 100% (B-BAL). Quantitative culture of blind sampling ofBAL resulted in a slightly lower sensitivity (73%) and a specificity of 96% for the diagnosis of pneu­monia. When analyzing pairs of B-BAL and NB-BAL samples we found similar results for both qualita­tive and quantitative bacteriology even if BAL fluids came from different lobes or the contralaterallung. These results suggest that "blind" sampling of BAL can be of value In clinical practice. Micro­scopic examination of BAL provided rapid (the day of BAL), sensitive (100%), and specific (88%)results, allOWing us to Introduce early and specific antibiotic therapy.

AM REV RESPIR DIS 1991; 143:1121-1129

IntroductionBacterial pneumonia is a frequent com­plication in patients requiring mechani­cal ventilation in an intensive care unit(lCU) and carries a significant mortali­ty. Craven and colleagues reported a 20%incidence of nosocomial pneumonia ina general ICU (1),but this figure is high­er in certain conditions, such as the adultrespiratory distress syndrome (ARDS)(2). The risk of developing ventilator­associated (VA)pneumonia rises linear­ly by about 1%/day, with most of thepneumonias occurring in the first 8 daysafter intubation (3, 4). The mortality rateof VA pneumonia reaches 50 to 70070(1, 3-6).

This condition presents a major diag­nostic challenge because of the low yieldof clinical criteria, such as fever, leukocy­tosis, or radiology (2, 3, 7). When theseparameters are combined the predictivevalue is higher, but still less than 100%,particularly in ARDS (7). The distinc­tion between tracheobronchial coloniza­tion and pulmonary infection is also dif­ficult if the standard semiquantitativemethod is used for culture of trachealaspirates (8). Using quantitative cultureswith a threshold of 107 bacteria/ml al­lows one to exclude false positive resultsdue to contamination or colonization (9).Salata and coworkers report a significantdifference between infected and colo­nized patients with this method (106 ver­sus 104 bacteria/ml), but a large overlapbetween the two groups results in a lowspecificity of this costly technique (5).The same authors showed that the find­ing of 3+ bacteria on a Gram stain ofbronchial secretions together with thepresence of elastin fibers on a KOH stainwas associated with a high probabilityof nosocomial pneumonia.

A more invasive approach has beenproposed by Chastre and colleagues (10),that is, bronchoscopy and quantitative

culture of a protected specimen brush(PSB). By using 103 bacteria/ml as athreshold the sensitivity was almost 90070and the positive predictive value above75% for the detection of VApneumonia(3, 11). The disadvantages of a PSB tech­nique are (1) high cost, (2) significantmorbidity (1 to 25070 incidence of pneu­mothorax or bleeding) (7, 11-13), (3) falsenegative results (14, 15), and (4) the 24­to 48-h delay in obtaining the results ofbacterial cultures (14). To overcome theproblem of delay Chastre and cowork­ers combined PSB with counting poly­morphonuclear leukocytes (PMN) con­taining intracellular bacteria in bron­choalveolar lavage (BAL) fluid (14). VApneumonia was associated with the pres­ence of more than 15% of infected PMN.

Johanson and colleagues evaluatedquantification of bacteria in BAL fluid

for the diagnosis of pneumonia in a ba­boon model (15). In this study the corre­lation was good between the quantita­tive culture of bacteria in BAL fluid andboth the quantitative cultures of the pul­monary lobe sampled as wellas the mostinfected lobe at the time of sacrifice.These results suggest that there are no

(Received in original form February 26, 1990 andin revised form November 28, 1990)

1 From the Division of Surgical Intensive Care,Department of Anesthesiology, the Divisions of In­fectious Diseases and Pneumology, Department ofMedicine, University Hospital of Geneva, Geneva,Switzerland.

2 Correspondence and requests for reprintsshould be addressed to Dr. Jerome Pugin or Dr.Peter M. Suter, Division of Surgical Intensive Care,University Hospital of Geneva, 24, rue Micheli-du­Crest, CH-1211 Geneva 4, Switzerland.

1121

1122 PUGIN, AUCKENTHALER, Mill, JANSSENS, LEW, AND SUTER

* Total points = CPIS (varies from 0 to 12 points).

TABLE 1

CPIS USED FOR THE DIAGNOSIS OF VA PNEUMONIA*

1. Temperature °C~ 36.5 and ~ 38.4 = 0 point~ 38.5 and ~ 38.9 = 1 point~ 39 or ~ 36.0 = 2 points

2. Blood leukocytes, rnrn?~ 4,000 and ~ 11,000 = 0 point< 4,000 or > 11,000 = 1 point + band forms ~ 500 = + 1 point

3. Tracheal secretions< 14 + of tracheal secretions = 0 point~ 14 + of tracheal secretions = 1 point + purulent secretion = + 1 point

4. Oxygenation: Pao/Flo2' mm Hg> 240 or ARDS = 0 point~ 240 and no evidence of ARDS = 2 points

5. Pulmonary radiographyNo infiltrate = 0 pointDiffused (or patchy) infiltrate = 1 pointLocalized infiltrate = 2 points

6. Culture of tracheal aspirate (semiquantitative: 0-1-2 or 3+)Pathogenic bacteria cultured ~ 1+ or no growth = 0 pointPathogenic bacteria cultured> 1+ = 1 point + same pathogenic bacteria seen

on the Gram stain> 1 + = + 1 point

significant differences in the bacteriolog­ic findings when sampling is done indifferent sites. This important point re­mains to be demonstrated in ventilatedpatients with a radiologically localizedinfiltrate. Johanson's group also ob­served a comparable specificity for theresults of BAL and PSB in the baboonmodel, but the sensitivity was clearly su­perior for BAL (100 versus 62070) (15).Torres and coworkers found an equiva­lent diagnostic yield with both techniquesin mechanically ventilated patients (11).Quantitative culture of bronchoscopicBAL (B-BAL) was used recently in im­munocompromised patients. Growth ofmore than 105 bacteria/ml in BAL fluidwas associated with a pneumonia (16, 17).

B-BAL needs expertise and training.Nonbronchoscopic, that is, "blind" BAL(NB-BAL) sampling is much simpler andwas first used in the acquired immuno­deficiency syndrome (18, 19) and then inintubated patients in the leu (20, 21).Qualitative bacteriologic results fromNB"BAL gave results similar to those ob­tained by PSB or postmortem culture (20,21). However, no attempt was made todifferentiate between colonized and in­fected patients.

The aims of the present study were firstto validate a new, blind sampling meth­od that is less costly and simpler to per­form by comparing quantitative bacteri­ology obtained by BAL with a fiberop­tic bronchoscope with BAL sampledblindly with a new catheter. Second, weattempted to determine early criteria forthe diagnosis of pulmonary infection bymicroscopic examination of BAL. Ourfindings suggest that blind BAL samplingcombined with quantitative bacteriolo­gy gives an accurate diagnosis of pneu­monia. Rapid diagnosis is possible usingthe Gram stain together with a stainingtechnique for elastin fibers in BAL fluid.

Methods

PatientsOver a 6-month period from January 1 toJune 30, 1989,28 ventilated patients at highrisk for developing a nosocomial pneumoniawere studied in the division of surgical inten­sive care at the University Hospital, Geneva,Switzerland. This is a 20-bed unit with 1,300admissions/yr. Patients were included in thestudy if they had been intubated and mechan­ically ventilated for more than 72 h and hada recognized predisposing pathology, such asmultiple trauma, cerebraltrauma, major emer­gency surgery, esophagectomy, or postopera­tive complications of cardiovascular surgery.Of these 28 patients 19 were studied once(680/0), 6 werestudied twice several days apart

(21 %), and 3 were investigated three times(11%). A total of 40 episodes were studied.

The APACHE II score was used to assessthe severity of the clinical condition at thetime of admission to the ICU (22). The per­centage of patients with ARDS and the num­ber of days ofprior and total mechanical ven­tilation were noted. The l-month mortalitywas recorded. Postmortem findings (if autop­sy was performed) were noted.

The study was approved by the committeefor ethics in human research of our institu­tion. Informed consent was obtained fromthe patient or, if this wasnot possible becauseof the clinical condition, by a member of thefamily or the treating physician.

Clinical VariablesThe following variables were recorded for the2 days before the study and on the day of in­vestigation: (1) body temperature; (2) bloodleukocyte count and number of band forms;(3) character of tracheal secretions (purulentor not) and quantity of tracheal aspirates (foreach endotracheal aspiration the nurses esti­mated the quantity of secretions from 0 to4+s; estimation of the volume of total secre­tions per day was calculated by adding all the+ values recorded over 24 h together; to en­sure a certain uniformity of this estimationonly nurses having at least 2 yr of continuoustraining in our ICU participated in this in­vestigation; the total number of tracheal aspi­rations also was recorded); (4) microscopicexamination (Gram stain) and semiquantita­tive culture of the bronchial secretions; (5)arterial oxygen tension/inspiratory fractionof oxygen (Pac/PI02); and (6) chest X-ray.The presence of bacteremia or positive cul­ture of the pleural fluid in the 5 days preced­ing and the 5 days following BAL were com­pared with bacteria cultured from sputum andin BAL fluids.

A clinicalpulmonary infection score (CPIS)

with a range of 0 to 12 was obtained fromthese clinical parameters (table 1).The rangeand weighting for temperature, leukocytes,sputum culture, and character as wellas chestX-rayweredetermined from published studies(2, 22-25). The range and weight for thePa02/Fl02 ratio and the sputum volume weredetermined by retrospective analysis of thefrequency of distribution.

Bronchoalveolar Lavage (BAL)The two BAL techniques were performed ina sequential manner in all patients, startingwith bronchoscopic BAL. The heart rate, sys­temic arterial pressure, and arterial oxygensaturation (Sa02) weremonitored throughoutthe procedure. The study was stopped if Sa02fell below 900/0 or if the patient becamehypotensive (mean systemic arterial pressurebelow 60 mm Hg). The majority of the cen­tral nervous system trauma patients had in­tracranial pressure monitoring. The study wasstopped if the cerebral perfusion pressure (thatis, mean systemic arterial pressure minus in­tracranial pressure) fell below 60 mm Hg.

Before starting BAL all patients were ven­tilated with 100% oxygen and sedated withmidazolam and morphine intravenously;head-injured patients weregivensodium pen­tothal. All patients received ventilatory sup­port during the study with a 20070 increasein tidal volume. The site for B-BAL was cho­sen according to chest X-ray appearance.B-BAL was performed in an area of local­ized pulmonary infiltration if present. Whena diffuse infiltrate or no infiltrate was seenon X-ray B-BAL was performed in the mostinflamed or purulent pulmonary segment de­termined by visual inspection. If no inflam­mation or purulent secretions were seenB-BAL was performed in the right lower ormiddle lobe. B-BAL was performed via theendotracheal tube using a swivel adaptor(Bodai Suction-Safe", SwivelY,Sontek Med-

ACCURATE DIAGNOSIS OF VENTILATOR-ASSOCIATED PNEUMONIA 1123

Fig. 1. Chest X-ray showing position of catheter introduced "blindly" and territory sampled by SAL. Films are takenafter injection of 5 ml contrast liquid. (Left) Antero-posterior view; (right), right oblique posterior view.

ical, Hingham, MA). Under visual control thebronchoscope was advanced in the directionof the chosen pulmonary segment until awedged position was achieved. Lavage wascarried out using two aliquots of 50 ml sterileisotonic saline. The bronchoscope was re­moved and ventilation with an FI02 of 100%continued for a further 10 min (26).

NB-BAL was then performed using a flex­ible, single-lumen, 14French polyvinyl cath­eter with a proximal Luer adaptor, stiffenedwith a metallic Teflonv-coated, guide wire(catheter for duodenography no. PVI4.0-75­P-NS-BBD; Cook A.G., Sempach-Station,Switzerland). The catheter was introduced ina blind manner through the same swivel adap­tor used for the B-BAL. It was advanced un­til a resistance (generally at a distance of 50to 60 em from the adaptor) was felt and main­tained in a wedged position. The guide wirewas then removed and the lavage performedwith two aliquots of 50 ml sterile isotonic sa­line. For NB-BAL as well as for B-BAL la­vage with a third aliquot of 40 to 50 ml wasperformed if there was a poor yield from thefirst 100ml. In severe pulmonary failure, thatis, ARDS patients, BAL was done with a to­tal of 60 to 75 ml. After NB-BAL the cathe­ter was maintained in the wedged position and5 ml contrast liquid (Omnipaques-Sou; Scher­ing A.G. Pharma, Berlin, Germany) was in­jected to determine the site of BAL. An an­teroposterior and oblique chest film were tak­en (figure 1). The site of NB-BAL was thenassessed in a blind manner by a radiologistwho had no knowledge of the patient's con­dition. BAL samples were sent to the bacteri­ology laboratory within 5 min and processedimmediately. The sequence B-BAL followedby NB-BAL was maintained for the wholestudy because the contrast liquid has bacteri­ostatic properties and could thereby producefalse negative results for the followingexamination.

BacteriologyThe 40 pairs of BAL samples were treated in

a similar manner. To a first part of BAL fluid2 ml of dithiothreitol (Dl'T) (Sputolysin'" Stat­Pak; Behring Diagnostics, San Diego, CA)was added, vortexed until homogenization,and then centrifuged. Supernatant (50 ul) wasplated on solid media using Spiral Plater" vol­ume deposition (Spiral System Instruments,Inc., Bethesda, MD). Sheep blood agar,colistin nalidixic acid (CNA) agar, chocolateagar, and McConkey's agar were incubatedin 5010 CO 2 for 72 h. Legionella, mycobacte­ria, mycoplasma, or viruses were not cultured.Colonies were quantified and identified con­ventionally and sensitivity tests performed.A bacterial index (BI) was calculated for eachsample according to Johanson's formula: BI= sum of log quantity of different bacteriacultured (15).

A manual microscopic count of cells wasdone on BAL fluid using standard techniques.BAL fluid was then cytocentrifuged at 1,200rpm for 5 min (Cytospin'" 2; Shandon South­ern Products, Cheshire, UK) and stained witha May-Griinwald-Giemsa for cell identifica­tion and differential count. On a Gram stainof cytocentrifuged material the quantity ofbacteria was determined with a standard scaleof 0 to 3+ according to the number of bacte­ria seen per oil-power field (5). Gram-negativeand gram-positive bacilli and cocci, yeasts,and the percentage of PMN containing in­tracellular bacteria weredetermined. The pres­ence or absence of elastin fibers was assessedwith an elastin stain followed by microscopicexamination.

Statistical AnalysisData are expressed as means ± standard devi­ation (SD). An unpaired Student's t test wasused to compare the mean of two groups, theMann-Whitney U test to compare groups withvariables not normally distributed, and apaired t test for paired values. Frequenciesand categories were compared with a X2 testwith the Yates correction. Linear regressionwas calculated using the method of leastsquares. Sensitivity, specificity, and predic-

tive values were calculated according to stan­dard formulas.

ResultsPatients and BAL Procedures

There was no significant difference inage, sex,diagnostic categories, APACHEII score, percentage of ARDS, or mor­tality between infected and noninfectedpatients (table 2).

No serious complications were notedduring or after the BAL procedures. Asignificant decrease in the Pao2/PIo2 ra­tio was observed in 40070 of patients,necessitating a temporary increase inPIo2. All patients recovered baselinevalues of oxygenation within 12 h. Noprocedure had to be stopped because ofhypoxemia, hypotension, or othercomplications.

Bacteriologic Analysis of BALA significant correlation was found be­tween the CPIS and the BI calculatedfrom Johanson's formula (r = 0.84,p < 0.0001 for B-BAL and r = 0.76,p < 0.0001 for NB-BAL; figures 2 and3) (15). When analyzing B-BAL sampleson the plot of CPIS versus BI (figure 2),two groups of results can be identified:one group with a CPIS >6, in whom 93070of the corresponding fluids had a cul­ture with a BI ~ 5 (defined as pulmo­nary infection) and a second group inwhom the CPIS was ~ 6 and all corre­sponding BI were < 5, patients withoutpulmonary infection. Using a CPIS > 6as clinical definition of pulmonary in­fection in ventilated patients, the sensi­tivityof the quantitative culture ofB-BALfluid assessed by the calculation of J0­

hanson's BI was 93070; the specificity andpositive predictive value were 100070. TheBI calculated on NB-BAL samples gaveslightly lower sensitivity (73%), specific­ity (96070), and positive predictive value(92%).

Comparison of paired BI calculatedfrom B-BALand NB-BAL fluids showedno statistical difference. This was un­affected by the site of BAL sampling. Thedifference of means of the BI of samplesobtained from the same lobe was 1.6 (p= 0.23), from a different lobe 0.5 (p =0.39), from the same lung 0.2 (p = 0.77),and from the contralateral lung 0.02 (p= 0.98). Also in those cases in whomB-BAL was performed at the site of aradiologically localized pulmonary in­filtrate and NB-BAL was sampled fromanother radiologically healthy site, theBI obtained by the two methods werenotsignificantly different (n = 12, mean BI

1124 PUGIN, AUCKENTHALER, MILl, JANSSENS, LEW, AND SUTER

TABLE 2

CLINICAL DATA AND DIAGNOSIS OF THE 28 PATIENTS STUDIED

No Pulmonary PulmonaryInfection Infection Total

(N = 15 Patients, (N = 13 Patients, Patientsmean ± SO) mean ± SO) p Value (N = 28)

Age, yr 51 ± 18 44 ± 21 NSAPACHE II score 12 ± 5 14 ± 6 NSSex, M:F 10:5 11:2 NS

(X2 = 0.43)

Duration of prior ventilation, days 5.3 ± 3.1 6.3 ± 4.7 NSDuration of total ventilation, days 8.7 ± 4.9 10.8 ± 6.8 NSDiagnosis

Polytrauma 3 8 11Cerebral trauma 2 2 4Complications after cardiovascular surgery 3 1 4Septic shock 1 1 2Esophagectomy 1 1 2Pancreatitis 2 0 2Peritonitis 3 0 3ARDS (%) 4 (26) 1 (7) NS 5 (18)

(X2 = 0.66)

Mortality rate, % 33 54 NS 42(X2 = 0.51)

18 ~

16

14 0c::0011I 12 No

~ G.l

~-a 10pulmonary Q)

.s~ - infection - d> 0

calli 8 0.;::~ :0

0 06 0

~~ ·"11 0 0 0 II"· threshold:

~= 4 0 0 0 0 BI=5

= 00 ~

Pulmonary2 9 8 0

:- infection -+

0 0 am an O'W0 2 4 6 8 10 12

from B-BAL - mean BI from NB-BAL= 0.5, p = 0.44). The paired compari­son of cellularity was also not significant­lydifferent if samples wereobtained fromthe same site or a different site.

Patients with pneumonia receivingprophylactic intravenous antibiotic ther­apy (n = 8) after contaminated surgeryor open fractures had a lower BI in BAL(6.8 ± 2.1)than those (n = 7) not receiv­ing antibiotics (9.6 ± 2.9, p < 0.05). Allbut one value was above the thresholdvalue of 5 (figure 4). Blood cultures werepositive in 2 of the 15patients with pneu­monia, with bacteria identical to thoseisolated from B-BAL and NB-BAL (Pa­tients 5 and 10). In 1 patient with pneu­monia culture from pleural fluid yieldedthe same microorganism as BAL fluids(Patient 8). Of the 7 patients who diedin the group of pulmonary infections, 3patients had an autopsy within 8 days af­ter the BAL procedures. The lungs ofthese 3 patients showed macroscopic andhistologic signs of moderate to severeconfluent bronchopneumonia. One ofthese patients also had positive blood cul­tures with the same organism (Pseudo­monas aeruginosa) present in sputumand BAL fluids. Of the 5 patients whodied in the noninfected group of patients,3 had an autopsy: 2 of them did not showany sign of pneumonia and the third, whodied 12days after BAL, had signs of mildbronchopneumonia.

The bacteria responsible for pulmo­nary infection in the group of patientswith pneumonia are summarized in ta­ble 3. Of the infections 87010 were poly­microbial and the predominant bacteriacultured quantitatively were the same inB-BAL and NB-BAL in 14of 15samples(93010). In the pneumonia group one iden­tical microorganism was cultured in bothBAL fluid and tracheobronchial secre­tions in 13of 15 patients (87%), but thepredominant bacteria of B-BAL fluidwere found in only 11 of 15tracheobron­chial aspirates, resulting in a sensitivityof 73%. Culture of tracheal aspirateresulted in a specificity of only 48010 (13samples with bacterial growth of the 25from patients without clinical pulmonaryinfection).

Extracellular bacteria wereseen in 93%of samples from patients with pulmonaryinfection but in only 12010 of samples inthe control group. Using semiquantita­tive determination on a Gram stain ofBAL, gram-negative bacilli and gram­positive cocci werefound more frequentlyin both B-BAL (p <0.0001) and NB-BAL(p < 0.0002) from patients with a pul-

Fig. 2. Relationship between bacterialindex, that is, the sum of log quantity ofbacteria (15)cultured from SAL obtainedby bronchoscopy and the clinical pulmo­nary infection score determined from 40investigations in 28 patients.

Fig. 3. Relationship between bacterialindex obtained by quantitative culturefrom nonbronchoscopic blind BAL andthe clinical pulmonary infection scoredetermined from 40 investigations in 28patients.

Fig. 4. Bacterial index (BI) in patientswith pulmonary infection depending onconcomitant antibiotic therapy for sur­gical prophylaxis or not. Open circles =individual values; closed circles with barindicate mean ± SD. Asterisk indicatesp < 0.05.

o '·11'" threshold:BI=5

No antibiotics(N=7)

o

I.V. antibiotics(N=8)

Clinical Pulmonary Infection Score

g 008 0 9

o 8 8 0 __ pul~Onary_o 0 am am 0 '" infection

2 4 6 8 10

Clinical Pulmonary Infection Score

o

:: f ~ol-----------0---- -----------------------0------------_ Threshold:o B~5

4

2

6

18 ~

016

14 0 0

12 Nopulmonary

0 010 -- infection -.

008 0 0

4

2

8

6

o

14

12

10

~ 0

TA

BLE

3c: :D ~

BA

CT

ER

IOLO

GY

OF

BA

LF

LUID

SO

F13

PA

TIE

NT

SW

ITH

15E

PIS

OD

ES

OF

PU

LM

ON

AR

YIN

FE

CT

ION

m cS

em

iqu

an

tita

tive

Qu

an

tita

tive

Cu

lture

Qu

an

tita

tive

Cul

ture

Pre

senc

eof

PM

N~

Cul

ture

ofof

B-B

AL

BI

ofN

B-B

AL

BI

Ela

stin

Fib

ers

X-r

ay-

Ioca

llze

dw

ithIn

trac

ellu

lar

z 0P

atie

ntT

rach

ea

lA

spira

te(c

fu/m

/)B

-BA

L(c

fu/m

/)N

B-B

AL

CP

ISin

BA

LF

luid

Infil

trat

eB

act

eri

ain

BA

LF

luid

C/) Cii

Abs

ent

No

Ye

s'

0H

.in

fluen

zae

++

260

H.

influ

enza

e9.

620

S.

aure

us2.

69

"'"S

.au

reus

++

+24

0S

tre

pto

cocc

us

sp.

20N

eiss

eria

sp.

< m40

0S

.pn

eum

onia

ez -i

160

C.

alb

ica

ns

F ~

2H

.in

fluen

zae

++

+10

6H

.in

fluen

zae

9.6

106

H.

influ

enza

e8.

910

Abs

ent

No

No

0 :D

S.

au

reu

s++

4x

103

S.

aure

us80

0S

.au

reus

~ C/) til

3B

ucca

lflo

ra+

++

1.2

x10

3S

tre

pto

cocc

us

sp.

5.9

103

Str

ep

toco

ccu

ssp

.7.

88

Abs

ent

No

No

0 0

S.

aure

us+

++

640

S.

aure

us10

3S

.au

reus

~60

H.

influ

enza

em c 'l

l4

Buc

cal

flora

++

5x

103

M.

mo

rga

nii

6.5

106

M.

mo

rga

nii

1712

Abs

ent

Yes

Yes

z mM

.mo

rga

nii

++

+60

0S

tre

pto

cocc

us

sp.

106

Str

ep

toco

ccu

ssp

.c: ~

105

H.

para

influ

enza

e0 z

5P

.ae

rugi

nosa

++

+10

5P

.ae

rugi

nosa

6.8

104

P.

aeru

gino

sa4

9P

rese

ntY

esY

ess

S.

eure

us«

60S

.au

reus

6H

.in

fluen

zae

++

+10

6H

.in

fluen

zae

610

6H

.in

fluen

zae

67

Pre

sent

Yes

Yes

E.

faec

alis

++

7B

ucca

lflo

ra+

++

104

Str

ep

toco

ccu

ssp

.9.

55

x10

3S

tre

pto

cocc

us

sp.

3.7

9P

rese

ntY

esY

es'

760

H.

influ

enza

e40

0A

cin

eto

ba

cte

rsp

.

8H

.in

fluen

zae

+10

4H

.in

fluen

zae

7.7

106

H.

influ

enza

e10

.711

Pre

sent

Yes

Yes

P.

vulg

aris

+12

0P

.vU

lgar

is54

0P

.vu

lgar

isC

.al

bica

ns+

+40

C.

albi

cans

100

C.

alb

ica

ns

9H

.in

fluen

zae

++

160

H.

influ

enza

e4.

310

4H

.in

fluen

zae

5.3

11A

bsen

tY

esN

oP

.vu

lgar

is+

+12

0P

.ae

rugi

nosa

20P

.ae

rugi

nosa

10P

.ae

rugi

nosa

++

+2.

8X

103

P.

aeru

gino

sa5.

110

5P

.ae

rugi

nosa

7.5

10P

rese

nt'[

Yes

Yes

40C

.al

bica

ns30

0C

.al

bica

ns

11S

.m

arsc

esen

s+

++

106

P.

aeru

gino

sa10

106

P.

aeru

gino

sa9.

311

Pre

sent

Yes

Yes

104

E.

coli

2x

103

E.

coli

12B

ucca

lflo

ra+

+5

x10

4H

.in

tiuen

zee

10.1

105

H.

influ

enza

e13

.711

Abs

ent

Yes

Yes

K.

oxyt

oca

++

+24

0K

.ox

ytoc

a5

x10

3K

.ox

ytoc

a1.

2x

103

Str

ep

toco

ccu

ssp

.10

5S

tre

pto

cocc

us

sp.

13S

.pn

eum

onia

e+

++

5.6

x10

3S

.pn

eum

onia

e13

.66

x10

4S

.pn

eum

onia

e10

.510

Abs

ent

Yes

Yes

H.

influ

enza

e+

106

H.

influ

enza

e50

0H

.in

fluen

zae

N.

men

ingi

tidis

++

+10

3N

.m

enin

gitid

is10

3N

.m

enin

gitid

is

14C

.a

lbic

an

s+

+10

5C

.al

bica

ns5

105

C.

albi

cans

59

Pre

sent

Yes

No

15H

.in

fluen

zae

+5

x10

4H

.in

fluen

zae

12.5

5x

104

H.

influ

enza

e14

.210

Pre

sent

Yes

Yes

S.

eure

us«

+18

0S

.au

reus

400

S.

au

reu

sS

.pn

eum

onia

e+

+5.

6x

103

S.

pneu

mon

iae

7x

104

S.

pneu

mon

iae

Def

initi

onof

abbr

evia

tions

:H

.inf

luen

zae

=H

aem

ophi

lus

influ

enza

e;S

.au

reus

=S

tap

hyl

oco

ccu

sau

reus

;S

.p

ne

um

on

iae

=S

tre

pto

cocc

us

pneu

mon

iae;

C.

albi

cans

=C

andi

daal

bica

ns;

M.

mor

gani

i=

Mor

gane

llam

orga

nii;

H.p

arai

nflu

enza

e=

Hae

mop

hilu

spa

rain

fluen

zae;

P.

aeru

gino

sa=

Pse

udom

onas

aeru

gino

sa;

E.

faec

alis

=E

nter

ococ

cus

faec

alis

;P

.vu

lgar

is=

Pro

teus

vulg

aris

;S

.m

arsc

esen

s=

Ser

ratia

mar

sces

ens;

K.

oxyt

oca

=K

lebs

iella

oxyt

oca;

N.

men

ingi

tidis

=N

eiss

eria

men

ingi

tidis

;pl

ussi

gns

=se

miq

uant

itativ

ees

timat

ion

ofnu

mbe

rof

bact

eria

(i.e

.•co

lony

-for

min

gun

itson

agar

plat

es).

•O

nly

foun

din

B-B

AL.

....t

Onl

yfo

und

inN

B-B

AL.

.... N U1

1126 PUGIN, AUCKENTHALER, MILl, JANSSENS, LEW, AND SUTER

TABLE 4

B-BAL AND NB-BAL·

Bronchoscopic BAL Nonbronchoscopic BAL(N = 40) (N = 40)

No Pneumonia Pneumonia No Pneumonia Pneumonia(N = 25, Mean ± SO) (N = 15, Mean ± SO) p Value (N = 25, Mean ± SO) (N = 15, Mean ± SO) p Value

Cellularity, rnm- 1,200 ± 1,500 3,100 ± 3,400 0.02 1,500 ± 1,500 2,900 ± 2,300 0.08PMN cells, mrn- 650 ± 900 2,400 ± 2,700 0.006 650 ± 900 2,400 ± 2,200 0.001Macrophages, rnrn- 290 ± 380 340 ± 270 > 0.05 260 ± 210 240 ± 220 > 0.05Lymphocytes, rnrn- 260 ± 550 440 ± 520 > 0.05 540 ± 1,470 241 ± 240 > 0.05Gram stain"

Gram positive cocci 0.08 ± 0.28 0.6 ± 0.5 0.0002 0.08 ± 0.28 0.87 ± 0.9 0.0003Gram negative bacilli 0.04 ± 0.2 1.1 ± 0.9 < 0.0001 0.12 ± 0.28 1.1 ± 1 < 0.0001Yeasts 0.08 ± 0.28 0.2 ± 0.5 > 0.05 0.08 ± 0.27 0.13 ± 0.35 > 0.05

% PMN with intracellularbacteria 0 8.3 ± 11.5 0.0008 0 11.7 ± 14 0.0001

Presence of PMN withintracellular bacteria (%) 0/25 (0) 11/15 (73) < 0.0001 0/25 (0) 9/15 (60) < 0.0001

(X2 = 21.4) (x2 = 16.1)

Presence of elastinfibers (%) 2/25 (8) 7/15 (47) < 0.01 3/25 (12) 8/15 (53) < 0.01

(X2 = 5.9) (X2 = 6.1)

Brl: 1.7 ± 1.6 8.1 ± 2.8 < 0.0001 1.6 ± 1.8 8.4 ± 4.2 < 0.000195% Confidence interval 0.9-2.1 6.6-9.7 0.85-2.3 6.1-10.7Range 0-4.2 4.3-13.6 0-5.2 2.6-17

• Analysis of cellularity, Gram stain, and culture of the SAL fluid (40 investigations in 28 patients).t Semiquantitative: 0-1-2 or 3 + .:j: L log of cultured bacteria.

monary infection than from noninfect­ed patients (table 4).

PMN with intracellular bacteria werefound in 73% in B-BAL and 60070 in NB­BAL fluids from infected patients. Nosamples in the control group had PMNwith intracellular bacteria (p < 0.0001).The percentage of PMN containing bac­teria in B-BAL fluid was 8.3 ± 11.5070and in NB-BAL 11.7 ± 14070 of all cellsin patients with pulmonary infection.

Elastin fibers were found in 47070 ofpulmonary infections compared with 8070in controls in B-BAL fluid (p < 0.01). InNB-BAL samples they were found in53070 of infected patients versus 12070 ofcontrol subjects (p < 0.01). In infectedpatients, elastin fibers were associatedwith gram-negative bacilli and radiolog­ically localized pulmonary infiltrates (ta­ble 3). The false positive results, that is,elastin fibers seen in patients without pul­monary infection, were sampled fromtwo patients with severeARDS.

Extracellular or intracellular bacteriaor elastin fibers were seen in 100% ofsamples taken from patients with pulmo­nary infection but in only 12070 of thesamples of the group without infection.

There was a significant difference be­tween the total cellularity (p <0.05) andquantity ofPMN (p <0.01) recovered inBAL fluid from infected and noninfect­ed patients, but not in the number ofmacrophages and lymphocytes (table 4).

Clinical VariablesOf the clinical variables recorded on theday of BAL and included in the clinicalpulmonary infection score (tables 5 and6), four show a significant differencewhen comparing infected with noninfect­ed patients: temperature, number ofbronchial aspirations that had to be per­formed per day, quantity of trachealsecretions, and Paa/FIa2 ratio, but notradiology, percentage of patients withpurulent tracheal secretions, blood leu­kocyte count, or band forms.

An analysis of the change in clinicalparameters between 2 days before BALand the day of BAL showed that patientswith pulmonary infection had an increasein the volume of secretions (p < 0.005),a decrease in the Paa/FIa2 ratio (p <0.05), a nonsignificant rise in body tem­perature, and no change in blood leuko­cyte count or band forms (table 6).

DiscussionThe management of VA pneumonia re­quires a rapid and accurate diagnosis.The gold standard for the diagnosis ishistology, but this is rarely available inICU patients. Most investigations of VApneumonia have therefore defined pul­monary infection using a number of clin­ical variables. If taken separately thesevariables do not permit one to distinguishpatients with colonization from those

with pneumonia. This is particularly truefor patients presenting with ARDS andthose requiring long-term ventilatorysupport for acute exacerbation of chronicobstructive pulmonary disease (COPD)(2, 10). Fever, leukocytosis, or X-ray ab­normalities are often due to a noninfec­tious cause in ICU patients, explainingtheir poor sensitivity and specificity (4,7, 10).The diagnostic yield of these vari­ables increases, however, when they arecombined.

In this report wedescribed a CPIS thatuses six easily obtained variables. Thisscore expands clinical judgment by in­cluding elements of chest X-ray and bac­teriology and permits us to quantify signsof pneumonia. A good correlation wasobserved between this score and the BIof quantitative culture of BAL fluid cal­culated according to Johanson's meth­od in VA pneumonia in baboons (15).Two groups of patients can be distin­guished by drawing a line between theCPIS values of 6 and 7. We suggest thatpatients with a CPIS > 6 have a pneu­monia, and all their bronchoscopicallyobtained BAL samples except one hada BI ~ 5. The sensitivity of detecting pul­monary infection by quantitative cultureof B-BAL was therefore 93070. The onlyfalse negative result was obtained in a pa­tient treated for sinusitis with antibiot­ics active against bacteria found in hislower respiratory tract and presenting

ACCURATE DIAGNOSIS OF VENTILATOR-ASSOCIATED PNEUMONIA

TABLE 5

CLINICAL VARIABLES OBTAINED ON THE DAY OF STUDY"

1127

Temperature, 0 CBlood leukocytes/rnm­Band forms, %Band forrns/mm!Number of aspirations/dayNumber of + tracheal secretions/dayPurulent tracheal secretions (%)

Pao/FI02' mm HgtPulmonary radiography (%)

No infiltrateLocalized infiltrateDiffuse infiltrate

Bacteriologic examination of tracheal secretionsGram stain§

Polymorphonuclear cellsGram-positive cocciGram-negative bacilliTotal bacteria seenll

Culture§Total bacteria cultured II

• Forty investigations in 28 patients.t ARDS not included.:t: Between no and !ocalized infiltrate.§ Semiquantitative: 0-1-2 or 3 + .IIGram-positive + gram-negative rods and cocci + yeasts.

No PulmonaryInfection

(N = 25, Mean ± SO)

38.1 ± 0.813,500 ± 5,500

10 ± 121,400 ± 2,100

4.7 ± 2.410 ± 7.5

11/25 (44)

270 ± 100

8 (32)5 (20)

12 (48)

1.7 ± 0.70.2 ± 0.4

0.08 ± 0.20.5 ± 0.9

0.7 ± 1

PulmonaryInfection

(N = 15, Mean ± SO)

38.8 ± 0.814,300 ± 5,500

12 ± 141,700 ± 2,000

7.2 ± 2.519 ± 4.5

12/15 (80)

190 ± 45

3 (20)12 (80)

o

2.4 ± 0.70.8 ± 11.7 ± 1.23.1 ± 2

3.7 ± 1.7

p Value

< 0.01NSNSNS

< 0.005< 0.001

0.057(x2 = 3.6)

< 0.01

0.063+(X2 = 3.45)

< 0.005< 0.01< 0.05< 0.0001

< 0.0001

TABLE 6

CHANGES IN CLINICAL VARIABLES BETWEEN 2 DAYS BEFORE BAL AND THE DAY OF BAL"

ity of 100070 in the detection of bacterialpneumonia.

As in Johanson's study, we observeda high incidence (87070) of polymicrobialcultures in VA pneumonia. The use ofthe BI, taking into account more thanone microorganism in BAL, seems to beimportant when comparing differentsamples. The reported incidence of poly­bacterial VA pneumonia seems lowerwhen the diagnosis is made by PSB (3).PSB probably recovers only a small 10­cal sample, which is less representativeof the whole infected region, whereasBAL allows collection of the microfloraof an entire lung segment (27). Chastreand colleagues observed false negativeresults using PSB with a threshold valueof 103 bacteria/mI, both positive or nega­tive results being obtained in clinicallyinfected patients (14). This group did not

with clear-cut clinical and radiologicsigns of pneumonia resulting in a CPISof 11. In patients with a CPIS ~ 6 theBI was consistently < 5, correspondingto a specificity and a positive predictivevalue of 100070 for the B-BAL. Sensitivi­ty, specificity, and predictive values areslightly lower for NB-BAL but still seemvalid for clinical use.

Our threshold value for BI = 5 is closeto that found by Johanson's group (15).In their study on ventilated baboons aBI ~ 6 was alwaysassociated with moder­ate to severepneumonia on histology, butno or only mild signs ofpneumonia wereobserved when the BI was < 6. Our in­dex of 5 is also similar to the thresholdvalue of 105 bacteria/ml cultured fromB-BAL fluid reported in immunocom­promised patients (16, 17), resulting ina sensitivity of 85 to 89070 and a specific-

Body temperature, 0 CBlood leukocyte count, rnrn"Band forms, rnm-Volume of tracheal secretions, NB of +Pao/Flo2 mm Hg

Definition of abbreviation: NB '" number .• Forty investigations in 28 patients.

No PulmonaryInfection

(Mean ± SO, N = 25)

0.37 ± 0.61450 ± 6,000

-200 ± 3,000-0.3 ± 6.7

-8 ± 57

Episodes ofPulmonary Infection

(Mean ± SO, N = 15)

0.89 ± 0.95- 1,400 ± 9,000

-90 ± 1,0006.8 ± 5.6

- 57 ± 83

p Value

0.0720.460.89

< 0.005< 0.05

find a clear threshold value using Johan­son's BI on BAL samples to differenti­ate colonization from pneumonia. Themean BI was 11.7 ± 6.2 in the 5 patientswith proven pulmonary infection, withall five values above our threshold valueof 5. However, the specificity of the BIwas low,with a high rate of false positiveresults (14). These different results areprobably due to other criteria used forthe diagnosis of pneumonia, resulting ina different classification of other typesof lower respiratory tract infection, suchas tracheobronchitis, possibly recordedas bronchial colonization (17,27-29). Inour study 3 of the 15episodes of pulmo­nary infection were not associated withinfiltrates on chest X-ray but with clearclinical signs of infection (CPIS of 8, 9,and 10)and BI of 5.9, 9.6, and 9.6, respec­tively, consistent with purulent tracheo­bronchitis (30). The second reason forthe discrepancy between our results ofBAL cultures and those of Chastre'sgroup (14) is a difference in the popula­tions studied. Our population consistedmainly of young multiple trauma pa­tients, whereas Chastre's group studiedmostly patients with COPD in whomheavy bronchial colonization is commonand could explain the high false positiverate found using the BI of BAL samplesin their study.

As in all studies of nosocomial pneu-

1128 PUGIN, AUCKENTHALER, MILl, JANSSENS, LEW, AND SUTER

monia we found a clear predominanceof aerobic gram-negativebacilli as causa­tive bacteria. Haemophilus influenzaewas detected in 53070 of patients in ourstudy, a well-recognized miroorganism in"early-onset nosocomial pneumonia" asa primary endogenous infection, origi­nating from oropharyngeal flora. Pollockand coworkers found H. influenzae in65070 of nosocomial pneumonia patients(30), Reusser and colleagues in 53% ofhead trauma patients (31), and Fagon andcoworkers in 33% of VApneumonia pa­tients (3). Chastre and colleagues report­ed a lower incidence of early-onset pneu­monia, probably because their patientshad a longer period of respiratory sup­port before BAL (15 ± 11 versus 6.3 ±4.7 days in our study).

Weobserved a good agreement for thetype of microorganism between B-BALand NB-BAL. The predominant bacte­ria cultured were identical in 93%, andno significant differences were found forthe BI or the cellularity in the two sam­ples. This wasalso true when B-BALwasperformed at the site of a localized pul­monary infiltrate and NB-BAL in adifferent lobe or the contralateral andradiologically healthy lung. This is inagreement with the data of Johanson'sgroup obtained in baboons, demonstrat­ing that BI calculated on B-BAL sam­ples correlated with both the culture fromthe lavaged lung lobe and the most in­fected lobe, that is, the greatest BI (15).This suggests that in ventilated patientsbacteriology and cellularity are similarin all pulmonary lobes and both lungseven when a localized infiltrate is pres­ent on chest X-ray. This is interesting andmay explain the good sensitivity andspecificity of a "blind" sampling tech­nique like BAL.

Results from quantitative cultures ofBAL can only be obtained after 24 to48 h, but the proportion of PMN withintracellular bacteria seen on a Gramstain provides a more rapid diagnosis. Inpneumonia more than 15% ofPMN con­tain intracellular bacteria, but this wasseen in only 1 of 13BAL samples ofpa­tients without pneumonia (14). In ourstudy no intracellularbacteria werefoundin patients without pneumonia but in730/0 of samples from patients with pneu­monia. The presence of bacteria withinPMN in BAL fluid seemsspecific (100%)but lacks sensitivity (73%). Adding ex­tracellular and/or intracellular bacteriaand/or presence of elastin fibers im­proved the sensitivity in the detection ofpulmonary infection to 100070, but the

specificity fell to 88%. Elastin fibers inBAL fluid were associated with gram­negative pulmonary infection and in­filtrates on chest X-ray. False positiveresults were obtained in two cases of se­vere ARDS in whom damage to pulmo­nary parenchyma is common. Our find­ings on elastin fibers in BAL fluid aresimilar to those reported by Salata andcoworkers (5) in sputum of ventilatedpatients.

Analysis of clinical criteria takenseparately resulted in significant differ­ences in the mean value for several vari­ables between the patients with and with­out pneumonia, with marked overlaps asreported previously (14). In our study,however, the association of clinical vari­ables in a score (CPIS) allowed us to dis­criminate patients with a high concen­tration of bacteria in BAL from thosewith low amounts of bacteria.

Standard cultures of tracheal aspirateswere of poor value to separate infectedfrom noninfected patients (positive pre­dictive value and specificity were 48%),confirming the results of earlier studies(8, 11).

In summary, this study describes avaluable clinical pulmonary infectionscore calculated from six easily obtainedvariables. This score correlated with thequantitative culture of BAL obtained byboth bronchoscopy and a catheter intro­duced blindly into the bronchial tree. Theclinical score allowed us to differentiatebetween infected and colonized patients.As previously suggested in a study onventilated baboons, we confirmed thatthe site of BAL sampling is not impor­tant for making a correct diagnosis.Quantitative bacteriology on BAL sam­ples gave identical results irrespective ofthe pulmonary segment sampled, evenin the presence of a localized infiltrateon the chest X-ray.Quantification of ex­tracellular and intracellular bacteria ob­served on the Gram stain and the searchof elastin fibers in the BAL fluid allowedrapid and accurate diagnosis, availablewithin 1 h after BAL. Further studiesshould now be done to evaluate if earlyand accurate diagnoses of VApneumo­nia will affect the outcome of thesepatients.

AcknowledgmentThe writers thank Mrs. Olga Delaspre andthe staff of the laboratory of bacteriology andof the surgical intensive care unit (UniversityHospital of Geneva) for their technical as­sistance and Dr. Kevin Gunning for his helpin the preparation of the manuscript.

References

1. Craven DE, Kunches LM, Kilinsky V, Lichten­berg DA, Make BJ, McCabe WR. Risk factors forpneumonia and fatality in patients receiving con­tinuous mechanical ventilation. Am Rev Respir Dis1986; 133:792-6.2. Andrews CP, Coalson 11, Smith JD, JohansonWG. Diagnosis of nosocomial bacterial pneumo­nia in acute, diffuse lung injury. Chest 1981; 80:254-8.3. Fagon J-Y, Chastre J, Domart Y, et al. Noso­comial pneumonia in patients receiving continu­ous mechanical ventilation. Prospective analysis of52 episodes with use of a protected specimen brushand quantitative culture techniques. Am Rev RespirDis 1989; 139:877-84.4. Langer M, Mosconi P, Cigada M, Mandelli M,the Intensive Care Unit Group of Infection Con­trol. Long-term respiratory support and risk ofpneumonia in critically ill patients. Am Rev RespirDis 1989; 140:302-5.5. Salata RA, Lederman MM, Shlaes DM, et al.Diagnosis of nosocomial pneumonia in intubated,intensive care unit patients. Am Rev Respir Dis 1987;135:426-32.6. Stevens RM, Teres D, Skillman JJ, Feingold DS.Pneumonia in an intensive care unit. Arch InternMed 1974; 134:106-11.7. Fagon J-Y, Chastre J, Hance AJ, et al. Detec­tion of nosocomial lung infection in ventilated pa­tients. Use of a protected specimen brush and quan­titative culture techniques in 147patients. Am RevRespir Dis 1988; 138:110-6.8. Johanson WG, Pierce AK, Sanford JP, Thom­as GD. Nosocomial infections with gram-negativebacilli. The significance of colonization of the re­spiratory tract. Ann Intern Med 1972; 77:701-6.9. Wilson MJB, Martin DE. Quantitative sputumculture as a means of excluding false positive reportsin the routine microbiology laboratory. J CUnPathol 1972; 25:697-700.10. Chastre J, Viau F, Brun P, et af. Prospectiveevaluation of protected specimen brush for the di­agnosis of pulmonary infections in ventilated pa­tients. Am Rev Respir Dis 1984; 130:924-9.11. Torres A, Puig de la Bellacasa J, Xaubet A,et al. Diagnostic value of quantitative cultures ofbronchoalveolar lavage and telescoping pluggedcatheter in mechanically ventilated 'patients withbacterial pneumonia. Am Rev Respir Dis 1989;140:306-10.12. Cartier F. Strategy in immunocompromisedpatients with pulmonary infiltrates. Intensive CareMed 1987; 13:87-8.13. Papin TA, Lynch JP, Weg JG. Transbronchialbiopsy in the thrombocytopenic patient. Chest 1985;88:549-52.14. Chastre J, Fagon J-Y,Soler P, et al. Diagnosisof nosocomial bacterial pneumonia in intubatedpatients undergoing ventilation: comparison of theusefulness of bronchoalveolar lavage and protect­ed specimen brush. Am J Med 1988; 85:499-506.15. Johanson WG, Seidenfeld 11, Gomez P, DeLos Santos R, Coalson JJ. Bacteriologic diagnosisof nosocomial pneumonia following prolonged me­chanical ventilation. Am Rev Respir Dis 1988;137:259-64.16. Thorpe JE, Baughman RP, Frame PT, Wes­seler TA, Staneck JL. Bronchoalveolar lavage fordiagnosing acute bacterial pneumonia. J Infect Dis1987; 155:855-61.17. Kahn FW, Jones JM. Diagnosing bacterial re­spiratory infection by bronchoalveolar lavage. J In­fect Dis 1987; 155:862-9.18. Caughey G, Wong H, Gamsu G, Golden J.Nonbronchoscopic bronchoalveolar lavage for the

ACCURATE DIAGNOSIS OF VENTILATOR-ASSOCIATED PNEUMONIA 1129

diagnosis of Pneumocystis carinii pneumonia inthe AIDS. Chest 1985; 88:659-62.19. Mann 1M, Altus CS, Webber CA, Smith PR,Muto R, Heurich AB. Nonbronchoscopic lung la­vage for diagnosis of opportunistic infection inAIDS. Chest 1987; 91:319-22.20. Papazian L, Martin C, Albanese J, Saux P,Charrel J, Gouin F. Comparison of two methodsof bacteriologic sampling of the lower respiratorytract: a study in ventilated patients with nosoco­mial bronchopneumonia. Crit Care Med 1989;17:461-4.21. Gaussorgues P, Piperno D, Bachmann P, etat. Comparison of nonbronchoscopic bronchoal­veolar lavage to open lung biopsy for the bacterio­logic diagnosis of pulmonary infections in mechan­ically ventilated patients. Intensive Care Med 1989;15:94-8.22. Knaus WA, Draper EA, Wagner DP, Zimmer­man lE. APACHE II: a severity of disease classifi­cation system. Crit Care Med 1985; 13:818-29.

23. Ledingham 1M, Eastaway AT, McKay IC, Al­cock SR, McDonald lC, Ramsay G. Triple regi­men of selective decontamination of the digestivetract, systemic cefotaxime, and microbiological sur­veillance for prevention of acquired infection inintensive care. Lancet 1988; 1:785-90.24. Stoutenbeek CP, van Seane HFK, MirandaDR, Zandstra DF. The effect of selective decon­tamination of the digestive tract on colonisationand infection rate in multiple trauma patients. In­tensive Care Med 1984; 10:185-92.25. Unertl K, Ruckdeschel G, Selbmann HK, etat. Prevention of colonization and respiratory in­fections in long-term ventilated patients by localantimicrobial prophylaxis. Intensive Care Med 1987;13:106-13.26. Klech H, Pohl W. Technical recommendationsand guidelines for bronchoalveolar lavage (BAL).Eur Respir 1 1989; 2:561-85.27. Faling Ll. New advances in diagnosing noso­comial pneumonia in intubated patients. Am Rev

Respir Dis 1988; 137:253-5.28. Garner lS, 1arvis WR, Emori TG, et at. Cen­ter for disease control definition for nosocomialinfections. Am 1 Infect Control 1988; 16:129-40.29. Brun-Buisson C, Legrand P, Rauss A, et at.Intestinal decontamination for control of nosoco­mial multiresistant gram-negative bacilli. Study ofan outbreak in an intensive care unit. Ann InternMed 1989; 110:873-81.30. Pollock HM, Hawkins EL, Bronner lR,Sparkman T, Bass lB. Diagnosis of bacterial pul­monary infections with quantitative protected cath­eter cultures obtained during bronchoscopy. 1 ClinMicrobiol 1983; 17:255-9.31. Reusser P, Zimmerli W, Scheidegger D, Mar­bet GA, Buser M, Gyr K. Role of gastric coloniza­tion in nosocomial infections and endotoxinemia:a prospective study in neurosurgical patients on me­chanical ventilation. 1 Infect Dis 1989; 160:414-21.