1993;104;1230-1235Chest J Rello, V Ausina, M Ricart, J Castella and G Prats pneumonia.etiology and outcome of ventilator-associated Impact of previous antimicrobial therapy on the

  http://chestjournal.chestpubs.org/content/104/4/1230

can be found online on the World Wide Web at: The online version of this article, along with updated information and services 

) ISSN:0012-3692http://chestjournal.chestpubs.org/site/misc/reprints.xhtml(without the prior written permission of the copyright holder.reserved. No part of this article or PDF may be reproduced or distributedChest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights

ofbeen published monthly since 1935. Copyright1993by the American College is the official journal of the American College of Chest Physicians. It hasChest

 © 1993 American College of Chest Physicians by guest on July 13, 2011chestjournal.chestpubs.orgDownloaded from

*Fr�,1) the Intensive Care, Microbiolog)� and Respiratory Depart-

ments, hospital (Ic Ia S. Creu i S. Pan, Universitat Autonomna deBarcelona, Barcelona, Spain.

Manuscript received October 13. 1992; revision accepted February23, 1993

1230 Impact of Previous Antimicrobial Therapy in Ventilator-associated Pneumonia (Reio at a!)

Impact of Previous Antimicrobial Therapyon the Etiology and Outcome of Ventilator-associated Pneumonia*Jordi Rello, M. D. , Ph . D. ; Vicen#{231}Ai�sina, Al. D. , Ph . D. ; Maite Ricart, RN.;

Joan Ca.s’tella, M.D. , Ph .D.; and Guilleni &ats, M.D. , Ph.D.

Objective: To define the influence of prior antibiotic use on

the etiology and mortality of ventilator-associated pneu-

monia (YAP).

Setting: A university hospital medical-surgical ICU.

Design: Prospective clinical study.

Methods: Over a 35-month period, we prospectively studied

129 consecutive episodes of YAP. Etiologic diagnosis was

established using a protected specimen brush and quanti-

tative culture techniques. We examined prognostic factors

by univariate and multivariate analyses using a statistical

software package (SPSS).

Results: The rate of YAP caused by Gram-positive cocci or

Haemophilus influenzae was statistically lower (p<O.OS) in

the patients who had received antibiotics previously, while

the rate of YAP caused by Pseudomonas aeruginosa wasstatistically higher (p<O.Ol). Patients died ofcauses directlyrelated to the infection in 18 (14.0 percent) episodes, P

aeruginosa being isolated in 9 of these fatal cases. Indeed,

we found that 27.7 percent (15/54) of patients who had

received prior antimicrobial therapy before the onset of

pneumonia died, compared with only 4.0 percent (3/75) of

those who did not. In the univariate analysis, the variables

significantly associated with attributable mortality were age

older than 45 years, use of corticosteroids, presence of

shock, hospital day of VAP over 9, antecedent COPD, and

a prior antibiotic use. A step-forward logistic regression

analysis defined only prior antibiotic use (p<O.0001,

OR = 9.2) as significantly influencing the risk of death from

YAP. The same result was obtained when severity was

included in the model. However, prior antibiotic use

entirely dropped out as a significant risk factor when the

etiologic agent was included in the regression equation.

Conclusions: Distribution of infecting microorganisms re-

sponsible for YAP differs in patients who received prior

antimicrobial therapy, and this factor determines a higher

mortality rate. We suggest a restrictive antibiotic policy in

mechanically ventilated patients with the purpose of reduc-

ing the risk of death from YAP. (Chest 1993� 104:1230-35)

MV = mechanical ventilation; VAP ventilator-associated pneu-monia

N osoconual pneumonia occurs in 0.5 to 2 percent

ofpatients hospitalized’2 and is the leading cause

of death from nosocomial infection. � Moreover,

intubated patients receiving mechanical ventilation

(MV) have an important increase in risk for pneumno-

nia,5 with the incidence of ventilator-associated pneu-

moma (VAP) ranging between 9 and 68 percent,

depending on the poptiIat�Ion studied. I,69

The impact on mortality is the most important

aspect ofany clinical problem. Identification of factors

For editorial comment see page 993

influencing mortality offers the possibility of improv-

ing prognosis through the identification of patients

with “high risk ofdeath” and the modification of so�ne

of these factors by medical intervention. The use of

multiple regression analysis helps to identify inde-

pendent prognostic factors for a disease as complex

and multifactorial as nosocomial pneumonia.

A high percentage of intubated patients have con-

comitant infections, which often leads to broad-spec-

trum antimicrobial therapy. Moreover, some atm-

thors’��’2 have recommended the use of prophylactic

antibiotics in intubated patients, because of the high

morbidity and niortality associated with VAP. In con-

trast, Fagon et al� have recently reported that previous

antimicrobial therapy 1)rior to the onset of VAP may

be associated with higher mnortality� However, to our

knowledge, the influence ofthis factor in the prognosis

of YAP has itot been studied previously using a

multivariate analysis.

Therefore, we performed a prospective study of 129

consecutive episodes of VAP to determine the influ-

ence ofa variety ofepidemiologic and clinical variables

on the outcome , by means of univariate and multivar-

iate analyses. Our specific goal was to provide current

inforniation oil the influence of antinucrobial therapy

before the onset of pneumonia on the frequency of

nncrobial etiologies and subsequent mortality.

NI ETIIOI)S

Population Study

Our intensive care unit (ICLT) is a 16-lied medical-surgical unit,

�vith an average of6()0 admissions per year, in a 1 ,0()0-1)ed university

hospital that serves as both a referral center and a first-line hospital.

 © 1993 American College of Chest Physicians by guest on July 13, 2011chestjournal.chestpubs.orgDownloaded from

CHEST I 104 I 4 I OCTOBER, 1993 1231

Table 1 -Summary ofindicationsfor Antibiotic Therapy

Indication Cases, No.

Previous nosocomial infection 19

Community-acquired pneumonia 10

Open fractures 8

Postoperative prophylaxis* 5

Septic shock 4

Pancreatitis 3

NFIt in transplant recipient 2

Miscellaneoust 3

*Prolonged for more than 48 h.

tNFI = nosocomial febrile illness.

�Tetarn,s, peritonitis, and fever ofunknown origin.

It is located in an urban area with a population of over 3 million.

During a 35-month period, all patients who developed pneumonia

in our ICU were considered eligible and were prospectively

evaluated by one of the investigators (JR.). We did not use any

selective decontamination regimen.

A diagnosis of pneumonia was considered when new and persist-

ent pulmonary infiltrates not otherwise explained appeared on chest

radiographs. Moreover, at least two of the following criteria were

also required: (1) fever �38#{176}C; (2) leukocytosis � 10,000/mm3; and

(3) purulent respiratory secretions. Pneumonia was considered

ventilator associated when its onset occurred after 48 h of MV and

was thus judged not to have been incubated before starting MV. To

analyze factors that might influence outcome, the following variables

were recorded: age, sex, severity prior trauma or surgery, under-

lying disease, the presence of COPD, diabetes, renal failure

requiring dialysis, cardiopathy, persistence of coma during MV, the

duration of MV prior to the development ofVAP, corticosteroid use,

and presence of shock (either prior as subsequent to the diagnosis

of yAP). All antimicrobials received for more than 48 h during the

10 days preceding the episode of VAP were recorded. Antibiotics

administered forless than 48 h, mainly for perioperative prophylaxis,

were not considered and the corresponding epis(xles of VAP were

classified as “free of exposition.’

Antecedent COPD was diagnosed using the standard criteria

recommended by the American Thoracic oc’3 Coma was

diagnosed when a Glasgow Coma Score lower than 9 was obtained’�

for more than 24 h. Criteria for corticosteroid use have been defined

previously.” Surgery or trauma was considered to be present if

recorded within 2 weeks prior to the episode. Presence of cardi-

opathy was considered if the patient had undergone surgery or if

an episode of angina or cardiac failure was previously diagnosed.

Diabetes was diagnosed if the patient received insulin previously

to hospital admission. Shock was defined as a systolic blood pressure

below 90 mm Hg accompanied by clinical signs of hypoperfusion,

such as oliguria and peripheral vasoconstriction. Severity of under-

lying medical conditions was stratified in three categories according

to the criteria proposed by McCabe and Jackson6 and in five

categories according to NNIS ICU severity-of-illness clinical clas-

sification codes. � Crude mortality included all deaths that occurred

in the ICU among patients with VA? Mortality was considered as

attributable to the pulmonary infection if death ensued before any

objective response to antimicrobial therapy or if the pulmonary

infection was considered a contributing factor to death in patients

with additional conditions.�

Microbiology

Fiberoptic bronchoscopic examination using a protected sped-

men brush” was performed on each of these patients within the

first 12 h after the development of a new pulmonary infiltrate,

except on weekends. A telescoping canula brush with a distal

polyethylene glycol occlusion (model BWF/10/70/90; Meditech Inc.

Watertown, Mass) was inserted through the inner suction channel

ofthe bronchoscope (model BF 10; Olympus Corp ofAmerica, New

Hyde Park, NY). This protected brush was advanced and aseptically

cut into a sterile tul)e containing 1 ml of sterile saline solution.

Specimens were taken to the microbiology laboratory immediately

after collection. The vial was then vortexed vigorously for at least

60 s to suspend all material from the brush. Two serial 100-fold

dilutions were carried out, and 0. 1-ml aliquots of the original

suspension and each dilution were inoculated on agar plates for

aerobic and anaerobic culture; one agar plate with selective buffered

charcoal-yeast extract medium for isolation of Legionella species

was included!� Bacterial count �1000 cfu/ml was the cutoff point

to diagnose pulmonary infections, according to the standards

adopted in previous studies.21 Bacterial identification and suscepti-

bility testing were performed by standard methods.�

Statistical Analysis

Contingency tal)les were analyzed using the two-tailed x2 test.

Multivariate analysis was performed using the stepwise logistic

regression model ofa software package (SPSS). using 0.05 as a limit

for entering new terms. The cutoff point for those variables with

more than two categories was chosen depending on the univariate

analysis results. Odds ratios (OR) were calculated using standard

methods.�’

RESULTS

During the period of the study, 150 episodes of

nosocomial pneumonia were identified in our ICU.

One hundred twenty-nine of them met criteria of YAP

and were prospectively followed. The mean ± SD age

of these patients was 49.5 ± 20.3 years; 91 were men

and 38 were women. Patients had received antimicro-

bial therapy for more than 48 h, in the 10 days

preceding the onset of YAP, in 54 of these episodes.

Indications for these antimicrobials are listed in Table

1 . Table 2 shows which type of antibiotics were used

prior to development of VAP, separated by etiologies,

for episodes with etiologic diagnosis.

Crude mortality was 34.1 percent. Patients died of

causes directly related to the pulmonary infection in

18 (14.0 percent) episodes. All patients with VAP

caused by Gram-positive cocci or Haemophilus influen-

zae recovered. Pseudomonas aeruginosa was the mi-

Table 2-Class ofAntibiotics Used Prior to DevelopmentofPneumonia in 89 Episodes With Established

Etiologk Diagnosis*

Microorganism C I A V Cl Other

Staphylococcus aureus 3 2 1 1 2

CNS I 1

Haemophilus influenzae 2 1 1

Pseudoinonas aeruginosa 6 9 5 6 1 7

Alcaligenesfaecalis 1 1 2

Serratia marcescens 2 1 3 2 1

Proteus mirabili,s 2 1 1 1 1

Acinetobacter calcoaceticus 2 1 2 1

Anaerobic flora 2 2 1

Fungi 2 1 1 1

*CNS = coagulase-negative staphylococci; C cephalosporins;

I = imipenem; A aminoglycosides; V vancomycin;

Cl = cloxacillin.

 © 1993 American College of Chest Physicians by guest on July 13, 2011chestjournal.chestpubs.orgDownloaded from

1232 Impact of Previous Antimicrobial Therapy in Ventilator-associated Pneumonia (Re!!o at a!)

Table 3-Characteristics ofPatients Who Died From VAP*

Case/

Age, yr/Sex Diagnosis pATB Microorganisms

1/43/NI Heart transplant Yes Aspergillus species

Candida species

2/59/M COPD ‘m�s P.seudonwnas a(’ruginosa

3/33/M Heart transplant Yes P aerUgiflosa

Serratia inarcescens

4176/NI CET Yes P acruginosa

5,�75/M Cardiogenic shock Yes Aspergilltms species

6/62/NI CAP Yes P aeruginosa

S mnarcescens

7170/NI COPD Yes Ac! netobacter

calcoaceticus

8174/M COPD Yes P aeruginosa

9/71fF COPD Yes A calcoaceticus

10/46/M Asthma Yes P aeruginosa

1 1/65/NI Cardiac surgery Yes P aeruginosa

12/72/F Pancreatitis Yes P aeruginosa

13/54/M Septic shock Yes Proteus mirabilis

14J21/M Multiple trauma Yes Uncertain

15/48/F Neurosurgery Yes Uncertain

16/68/M Cardiac surgery No Uncertain

17/51/NI Multiple trauma No S marcescens

18/71/M Thoracic surgery No P aeruginosa

*VAP = ventilator-associated pneumonia; CET cranioencephalic

trauma; CAP = commumty-ac(�uired pneumonia; COPD chronic

obstructive pulmonary disease; pATB = previous antibiotic therap);

croorganism most frequently isolated among fatal

episodes, being present in nine of them. Details of

these 18 episodes are shown in Table 3.

A total of 1 13 microorganisms �vere cultured from

protected specimen brushing in significant (� 1000

cfu/ml) concentration. Twenty-three episodes were

polymicrobial infections. Table 4 catalogues all epi-

sodes l)y whether or not receiving antibiotics, the

number of positive cultures in each group, and the

outcomes. Gram-positive cocci represented 49. 1 per-

cent of isolates in the group fi-ee of antimicrobial

exposure, compared with 13.4 percent in the group

with previous antibiotic therapy (p<O.OS). Staph yb-

coccus aureus accounted for 75.6 percent ofall Gram-

positive cocci isolated, and the most frequent micro-

organism in patients without prior antibiotic use. All

S aureus strains were penicillinase producing but

sensitive to all other antibiotics tested. Haernophibus

influenzae was the second most frequent microorgan-

i5IT1 (27.8 percent of isolates) among patients without

prior antimicrobial therapy but was an infrequent

finding (5.7 percent of isolates) in episodes with

previous antimicrobial exposure (p<O.O5). In contrast,

Gram-negative bacilli - excluding H influenzae - rep-

resented 69.2 percent ofisolates among episodes with

antibiotic exposure prior to the onset of YAP but only

represented 19.6 percent of isolates in the opposite

group. Indeed, Paeruginosa, the Gram-negative bacilli

most often isolated, represented only 4.9 percent of

isolates in patients without previous antibiotic expo-

sure but represented 40.3 percent of isolates in

patients subjected to prior antimicrobial treatluent

(p<O.Ol), l)eing present in up to 50 percent of VAPs

with etiologic diagnosis developed in this group of

patients.

Table 4-Microorganisms Isolated in 129 Episodes of VAP*

Microrganism

Isolates

- Mortality,t

No.

,�pATB No pATB Total

c;ram-f�Ositi%’e cocci�

Staphylococcus aureus 6 22 28 -

Streptococcus pneunumiae 0 5 5 -

bnt(’rococcusfaecalis 0 2 2 -

Coagulase-negative staplwlococci 1 1 2 -

c;ramii-mmegative l)acilli

Hacinophilus influenzaet 3 17 20 -

P.seudonmonas aeruginosa* 21 3 24 9

Alcaligenesfaecalis 3 4 7 -

Serratia mnarcescen.s 5 0 5 3

&Ot(’U.S mniralnli.s 4 0 4 1

Acinetol�u:ter calco(zceticu.s 3 1 4 2

bscho’riclmia coli 0 3 3 -

Citrohacterfrcundii 0 1 1 -

Anaerobic flora 3 1 4 -

Fungi

Candida species 1 1 2 1Aspergillus species 2 0 2 2

Uncertain 13 27 40 3

*pATB = pre\i�tIs antibiotic use.

tDirectly related tO) the ventilator-associated pneun)onia.

�I)<0.05.§p<O.Ol. (Both p values c�fl)l)are isolates in the group with pATB in respect to the group with no ATB.)

 © 1993 American College of Chest Physicians by guest on July 13, 2011chestjournal.chestpubs.orgDownloaded from

48 (37.2) 3 (6.2) 1

81 (62.7) 15 (18.5) 3.6

91 (70.5� 15 (16.5� 2.3

38 (29.4) 3 (7.9) 1

22 (17.0) 1 (4.5) 1

107 (82.9� 17 (15.9) 3.9

64 (49.6) 7 (10.9� 1

65 (50:3) ii (16.9) 1.4

44 (:34.1) 3 (6.8) 1 NS

85 (aSS) 15 (17.6� 2.9

61 (47.2) 7 (11.5) 1

68 (52.7) 1! (16.2) 1.4

Age, yr

<45

>45

(;em)der

NIale

Fenlale

I.Jm�lerlving condition

NF

1JF/RFSeveritvll

Codes A, B. C

Codes I). ETrammm��i

Yes

No

Surgery

Yes

No

Prior antil)iotic

therapy

Yes

No

Corticosteroid use

Yes

No

hospital day of VAP

5;9 d>9d

I)iala-tes

Yes

No

Renal fail,mre

Yes

No

Shock

Yes

No

(�)nbl

Yes

No

c;�mrdi )pathv

Yes

No

c;()PI) antece(lent

Yes

No

54 (41.8)

75 (58.1)

26 (20.1)

103 (79.8�

15 (27.8)

3 (4.0)

7 (26.9)

11 (10.7)

14 (10.8) 4 (28.6) 2.8

115 (84.1) 14 (12.2) 1

15 (ll.(i� 5 (:3:3:3) 3.8114 (S8.;3� 13 (12.8) 1

NS

0.02

19 (14.7) :3 (15.8) 1.1

110 (85.2) 15 (l3.6� 1

24 (18(i) 8 (;33.:3) 3.0 0.0()2

105 (81.3) 10 (9.5) 1

*(�)PD = chronic obstructive l)mIln1�m1ar\ (liseas \AP - ventilator-

assx.’iated I)neIIIla)Ilia; NF = Iu)nlatal: iT J” mmltimnotelv fatal; RF

rapidl� fatal; NS = not significant.

tPercentage within (‘�lch categor��

:1:Percentage of de’aths Iron) pn(’lIIIIiOIiia svitliin o’pisodes in each

group.

§\Vithin each category au odds ratiO) of 1 svas arl)itrarllv assigmied to

the variable sulxlivision with the lowest risk rate.

INNIS ICU severitv-ofillness clinical classific.,tion.

Univariate analysis of the 15 climmical and epidemio-

logic variables included in this stud� is shown in Table

5. The category With the lo�vest mortality rate ��‘as

arl)itrarily assigned to ha�’e a relative risk of death of

CHEST I 104 I 4 I OCTOBER, 1993 1233

Table 5-Prognostic Factorsfor VAP: Univariate Analysis* 1 . Age older than 45 years, corticosteroid use, pres-

ence of shock, hospital day of YAP over 9, antecedent

COPI), and prior antibiotic use were associated with

a significantly greater risk of death in the univariate

analysis. In contrast, the remaining nine variables

0.05 studied were iiot significant.The data were further analyzed using a stepwise

logistic regression model. The dependent variable was

NS attributable mortality; the independent variables were

the dichotomous variables found to he significant by

NS univariate analysis. After adjustment for confoundingfactors, only prior antibiotic use (p<0.000l , OR = 9.2)

was identified as significantly influencing the risk of

NS death from VAP A separate logistic regression analysis

on mortality was performed again with severity as o�e

of the independent variables included and it gave the

same results. This analysis was repeated for the 89

episodes ofVAP with an established etiologic diagnosis

NS with the etiologic cause of pneumonia as one of the

variables included. For this I)t1�P�se, etiologies were

classified as “high-risk” pathogens when they were

9.2 0.0(X)l associated with attributable mortality (P aeruginosa,S inarcescens, A calcoaceticus, P mirabilis, and fungalinfections). In this analysis, prior antibiotic use entirely

3.0 0.03 . �. .

urop�e�i out as a signmcant prognostic tactor anu itwas replaced by high-risk pathogens.

66 (51.1) 4 (6.1) 16:3 (48.8) 14 (22.2) 4.4 DIS(:USSION

In this Stu(IV, we analyze the relation of a variety of5 (:3.8) 1 (20.0) 1.5 NS . . � . ‘ . .

124 (96 1) 17 (13 7) 1 clmIcal-epiuemioioglc tactors to outcome or VAP A -

though nR)rtahty in patients with nos()comial pneu-monia has been reported very high, there is evidence

to suggest that the crude mortality may be more a

function ofthe severity ofthe underlying disease than

lung infection p� se.24 Several severity of illness

indices are available for critically ill patients and we

59 (45.7) 5 (8.5) 1 NS stratify Ofl� patients according to the criteria used by

70 (54.2) 13 (18.6) 2.4 McCabe and Jacksonm6 and to the codes defined by

, . Emnori et al.’7 The effect of alternative indices basedNS OH organ failure, such as the APACHE score, were not

evaluated. Since crude mortality appears to be an

inappropriate criterion to evaluate outcome for YAP,

we used only the attributable mortality for statistical

analysis. According to the univariate analysis, age

older than 45 years (p = 0.05), use of corticosteroids

(p = 0.03), presence of shock (p = 0.02), hospital day of

VAP O’Ver 9 (p = 0.008), antecedent COPD (p 0.002),

and prior exposure to antibiotics (p = 0.()()01) were

significantly associated with fatality by YAP None of

the other variables examined exerted a statistically

significant effect on mortality from VAP However,

IflOst ofthese variables are interrelated and, therefore,

a multivariate statistical study should he performed to

identify those factors that may independently info-

ence the mortality. In 1)0th multivariate analyses of

the 129 episodes studied, the presence of a prior

Episodes Attributable

of \‘A� NIortalit�� Odds p

\�oriable’ No. (��i)1� No. (%)� I1atio� \�mlmie

 © 1993 American College of Chest Physicians by guest on July 13, 2011chestjournal.chestpubs.orgDownloaded from

1234 Impact of Previous Antimicrobial Therapy in Ventilator-associated Pneumonia (Re!!o et a!)

antimicrobial treatment (p<O.000l) was the only factor

that independently influenced mortality. Previously,

Fagon et al,� in a prospective study of 52 episodes of

YAP, reported that the overall mortality in a group of

31 patients who had received antimicrobial therapy

before the onset of pneumonia was 83 percent, corn-

pared with a mortality of 48 percent in the group of

21 patients who had not received prior antibiotics

(p<O.Ol). Our data agree with their suggestion that

antimicrobial therapy before onset of VAP may be

associated with a negative impact on outcome.

Furthermore, a strong relationship between the use

ofantibiotics prior to the onset ofVAP and the etiologic

agent is clearly observed in our study Our finding that

prior antibiotic use entirely dropped out as a significant

risk factor when the etiologic agent was included in

the logistic regression analysis demonstrated that the

increased mortality associated with prior antibiotic

use is due to the selection of more lethal organisms.

Indeed, Gram-positive cocci and H influenzae repre-

sented more than three quarters of isolates among

episodes free of antimicrobial exposure . However,

these agents were an infrequent etiology among pa-

tients subjected to prior antimicrobial therapy, and a

high proportion of episodes in this group were due to

P aerugino.s’a or multiresistant Gram-negative bacilli.

Suppression ofthe normal bacterial flora by antibiotics,

with the subsequent emergence of a resistant Gram-

negative flora, may explain this observation. Fagon et

al� also reported that pneumonia with P aerugino.ca or

Acinetobacter species was higher in the 31 patients

who had received prior antibiotics (65 vs 19 percent,

p<O.Ol). Other studies have reported the influence of

antibiotics in the selection of microbial flora and in

determining etiologic patterns of nosocomial I)11e11

monia . �27

A close relationship between the agent responsible

for nosocornial pneumonia and mortality has also been

previously observed by other investigators.58� In our

study, this observation cannot be related to made-

quate antibiotic treatment for selected etiologies,

except for the two patients with fungal pneumonia,

since all patients received a broad-spectrum empiri-

cal treatment , including antipseudomonadal coverage.

Several previous studies have reported the relation-

ship between mortality and patients with Gram-

negative hacillary pneumonia.329”#{176} In our study, the

risk of mortality was very high in those patients with

YAP caused by P aeruginosa, multiresistant Gram-

negative bacilli, or fungi. Indeed, P aeruginosa was

isolated in 60 percent of fatal episodes with etiologic

diagnosis. Conversely, when YAP was caused by Gram-

positive cocci or by H influenzae, the prognosis was

benign. The large increase of high-risk pathogens in

patients who received prior antimicrobial therapy may

explain the relationship between mortality and prior

antil)iOtiC use.

Antibiotic therapy has a great ecologic impact.

Broad-spectruml3 antibu)tic tlwrapy; used in most ICUs,

i�i-iay alter patients’ niicroflora, leading to airway cob-

nization and tilti niatelv i nfection with miiethicillin-

resistant staphylococci , multiple resistant E nterobac-

teriaceae , psetidomonads, and ye;tsts.23’ u Most

nosocornial outbreaks caused liv resistant pathogens

l)egan in the small fraction of I)atientS hospitalized in

the ICU and afltii)iotiC Iresstire was usually found to

be one of the niost important factors preclisposing

these patients to infection with resistant organisrns.�Iu

Antibiotics tiot OIIIV alter colonization in the orophar-

ynx and gastrointestinal tract, but they mna�’ also have

deleterious effects 013 the host irnniimne response to

infection.�5 Some clinicians have opted f�r the liberal

LIS(’ of l)roacl-spectrunl aI�tin�icrol)iab agents in ole-

chanicall’v ventilated I)atiellts when the� developed a

febribe nosoconlial episode, or even f�r 1)roPhyl�Lxis of

nosocoiiiial 1)�eu iiionia . \Ve agree �vith Johan SOfl3() that

such practices are expensive, niav cause avoidal)le

side effects, an(l compromise efforts to document

causative agents precisely in future infections. Fur-

thermore, Our current results suggest that this strategy

may be ass()ciated with a higher mortality, directly

related to infection if such patients developed a YAP

Consequentl�; we suggest the development of specific

guidelines for antimicrobial therapy of infections in

the ICU and an ai’ltiI)iOtiC control policy based on the

restriction of broad-spectrum agents. We support the

proposition of Flaherty and \Veinstein2 that the use of

l)road-spectrunl antibiotics in critically ill patients

should be surveyed and approved by a designated

antibiotic expert who should l)e an infectious (liSease

I)hvsiCial1 or a critical care physician with expertise inantimicrobial therapy and infection control . I n our

opinion, avoidance of unnecessary administration of

antibiotics should form part of the reconlrnended

procedim res in tile treatment of mechanically ventilated

patients.

ACKNOWLED(;MENT: \Ve thank W c;. JOh�sm�sOm), NI . D. , NI PH.,and ;. Verger, M.D. , for helpful simg�estions concerning themanuscript. \Ve also thank meml)ers of the ICU for their coopera-tion.

RE FE RE N( :ES

1 Craven DE, Kunches LM, Kilinsky � Lichtenherg DA, NIake

BJ, NlcCabe \VR. Risk factors for pm1e1In�)m)ia and fatality in

patiel)ts receiving continuous niechanical ventilation. An RevRespir Dis 1986; 13.3:792-96

2 Flaliertv JP, \Veinstein HA. Infection control am�l pneumonia

prophylaxis strategies in the intensive care unit. Semain Respir

Infect 1990; 5:191-203

3 Pennington JE. Nosoconiial resI)irator\ infection. Iii: Nlandell

(;L, Douglas Rc; Jr. Bennett JE, eds. Principles an�1 l)r�Ictice of

infectious diseases. Ness’ ‘turk: John \Vile� & Sons, 1985; 1620-

25

4 Garibaldi BA, Britt NIR. Coleman NIL, Reading JC. Pace NL.

Risk factors for postoperative pneumnonia. Am J NIed 1981;

70:677-80

 © 1993 American College of Chest Physicians by guest on July 13, 2011chestjournal.chestpubs.orgDownloaded from

CHEST I 104 I 4 I OCTOBER, 1993 1235

5 Cehis R, fo)rres A, Gatell JNI, Almela NI, Rodrigmmez-Roisin R,

Agusti-Vidal A. Nosx�mial pnetmmonia: a mtmltivariate analysis

of risk and prognosis. Chest 1988; 93:318-24

6 Seidenfeld JJ, Pohl DF, Bell RC, Harrys GD. Incidence, site

and O)IltcO)me O)f infections in patiemits with the adult respirato)r\

distress syndrome. Am Rev Respir Dis 1986; 134: 12-6

7 Torres A, Azmiar R, Gatell JM, Jinienez P. Gonzalez J, Ferrer A,

et al. Incidence, risk and prognosis factors of no)so)co)mial

pmieunlo)nia in mechanically ventilated patients. Am Rev Respir

Dis 199(); 142:523-28

8 Fagon JY, Chastre J, Domnart Y, Trouillet JL, Pierre J, Dame

Cli, et al. Nosox.omial pneunio)nia in patients receiving co)ntin-

IlOtis mnechamiical ventilatiomi: pro)spective analysis of52 episoxies

�5�itl� use O)f a pro)tected specimen brush and quantitative culture

techniques. Am Rev Respir Dis 1989; 139:877-84

9 Meduri CU. Ventilator asso)ciatecl � in patients with

respirato)ry failure: a diagnostic approach. Chest 1990; 97:1208-

19

10 \Veinstein RA. Selective intestinal decontamination: an infection

control mneasure whose time has come? Ann Intern Med 1989;

110:853-55

11 Van Saemie HKF, Stoutenbeek C� Lawimi P, Ledingham IMcA.

Update in imitemisive care and emergency medicine: infection

contro)l hw selective decontamination. 1st ed. Berlin: Springer-

Verlag, 1989

12 Comit#{233} de Consensus. Seventh Conference de comsensus en

r#{233}animnatio)n et medicine d’imrgence: microbial selective decomi-

taminatio)n in intensive care patients. Paris, December 13-14,

1991

13 American Thoracic Societ�� Standards for the diagnosis and care

of patients with chronic obstructive pulmonary disease (COPD)

and asthma. Ama Rev Respir Dis 1987; 136:225-44

14 Rimel R’iV, lvson G\V. The neumologic examinatio)mi in patients

�ith central miervous system trauma. J Netmrosurg Nurs 1979;

12: 148-52

15 Rello J, Qimintana E, Ausina Y Puzo C, Net A, Prats G. Risk

factors for Staphylococcus aureus mio)so)eomial pneurno)nia in

critically ill patients. Am Rev Respir Dis 1990; 142:1320-24

16 McCabe WR, Jackson GG. Gram-negative l)acteremia: etio)logy

and ecologs: Arch Intern Med 1962; 110:847-55

17 Emori GT, Cmilver DH, human TC, Jarvis \VR, White JW Olson

DR, et al. National noso)co)mial infections surveillance system

( NNIS): description ofsurveillance methods. Am J Infect Comitrol

1991; 19:19-35

18 Fagoii JY, Chastre J, liance AJ, Gimigimet NI , Troimillet JL, Doniart

Y, et al. Detection o)f no)so)eo)mnial lung infection in ventilated

patients: use O)f a I)rotectecl specimen brmmsh and quantitative

culture techniques in 147 patients. Am Rev Respir Dis 1988;

138:110-16

19 Wimberley NW, Bass JB, Boyd BW, Kirkpatrick MB, Serio BA,

Pollock JIM . Use O)f a bronchoscopic protected catheter brush

for the diagnosis of pimimnonary infections. Chest 1982; 82:556-

62

20 Edelstein PH. Improved semiselective medium for isolation of

Legionella pneunwphila from contaminated clinical and enviro)n-

mental specimens. J Clin Microbiol 1981; 14:298-303

21 Chastre J, Viau F, Brun P. Pierre J, Dange MC, Botichaine A.

Prospective evaluation of the protected specimen brush for the

diagnosis ofpulmonary infections in ventilated patients. Am Rev

Respir Dis 1984; 130:924-29

22 Lennette EH, Bullows A, Hausler WJ Jr. Shadomy HJ. ManualO)f clinical microbiology. 4th ed. Washington: American Society

for Microbiologs; 1985

23 Schlesselman JJ. Case-control studies: design, conduct, analysis.

New York: Oxford University Press, 1982

24 A’Court CH, Garrard ChS. Nosocomial pneumomiia in the

intensive care unit: mechanisms and significance. Thorax 1992;

47:465-73

25 Louria DB, Kaminski T The effects of four antimicrobial drug

regimens oti sputum superinfection in hospitalized patients. Am

Rev Respir Dis 1982; 85:649-85

26 Carratala J, Pallares R, Verdaguer R, Santin M , Mascaro J,Manresa F, et al. Risk factors for noso)co)mial pneumococcal

I)netlmo)mlia. Presented at the 31st Interscience Conference onAntimicrobial Agents and Chemotherapy, Chicago, October

1991

27 Rello J, Ricart M, Ausina V, Net A, Prats G. Pneumonia due to

Haenwphilus influenzae among mechanically ventilated patiemits:

incidence, otmtcome and risk factors. Chest 1992; 102: 1562-65

28 Graybill JR, Marshall LW, Charache P. Wallace CK, Melvin VB.

Nosox�omial pneumonia: a continuing major problem. Am Rev

Respir Dis 1973; 108:1130-40

29 Stevemis RM, Teres D, Skillman JJ, Feingold DS. Pneumonia iii

an intensive care unit. Arch Intern Med 1974; 134:106-11

30 Gross PA, Neim HC, Aswapokee P. Van Antwerpen C, Aswapokee

N . Deaths from nosocomial infection: experience in a university

hospital and a community hospital. Am J Med 1980; 68:219-23

31 Sheagren SN . Staphylococcus aureus: the persistent pathogen.

N Engl I Med 1984; 310: 1437-42

32 Peacock JE Jr, Marsik FJ, Wenzel RE Methicillin-resistant

Staphylococcus aureus: introduction and spread withimi a hospi-

tal. Ann Intern Med 1980; 93:526-32

33 Maki DG. Risk factors for nosocomial infection in intensive

care: devices vs nature and goals for the next decade. Arch

Intern Med 1989; 149:30-5

34 \Veinstein BA. Endemic emergence o)f cephalosporin-resistant

Entemobacter: relation to prior therapy. Infect Control 1986;

7(suppl):120-23

35 Hauser \VE JR. Remington JS. Effect on antibiotics on the

immune response. Am J Med 1982; 77:711-16

36 Johanson WIG Jr. Ventilator-associated pneumonia: light at the

end ofthe tunnel. Chest 1990; 97:1026-27

 © 1993 American College of Chest Physicians by guest on July 13, 2011chestjournal.chestpubs.orgDownloaded from

1993;104; 1230-1235ChestJ Rello, V Ausina, M Ricart, J Castella and G Prats

ventilator-associated pneumonia.Impact of previous antimicrobial therapy on the etiology and outcome of

 July 13, 2011This information is current as of

 

http://chestjournal.chestpubs.org/content/104/4/1230Updated Information and services can be found at:

Updated Information & Services

http://chestjournal.chestpubs.org/content/104/4/1230#related-urlsThis article has been cited by 51 HighWire-hosted articles:

Cited Bys

http://www.chestpubs.org/site/misc/reprints.xhtmlonline at: Information about reproducing this article in parts (figures, tables) or in its entirety can be foundPermissions & Licensing

http://www.chestpubs.org/site/misc/reprints.xhtmlInformation about ordering reprints can be found online:

Reprints

the right of the online article.Receive free e-mail alerts when new articles cite this article. To sign up, select the "Services" link to

Citation Alerts

slide format. See any online figure for directions. articles can be downloaded for teaching purposes in PowerPointCHESTFigures that appear in Images in PowerPoint format

 © 1993 American College of Chest Physicians by guest on July 13, 2011chestjournal.chestpubs.orgDownloaded from