Incidence, risk factors, and outcome of ventilator-associated pneumonia

0 downloads 0 Views 165KB Size Report
There are a few studies that report risk factors for death of ventilated ... pattern to that found by us, Luna et al [25] reported that the ... mallén); G Fernández Cid (Hospital E Tomú, Buenos Aires); H ... Raimondi (Sanatorio Mater Dei, Buenos Aires); E Romero ... Valle de Lilly, Cali); R Panesso (Clınica Las Américas, Medellın);.
Journal of Critical Care (2006) 21, 56 – 65

Incidence, risk factors, and outcome of ventilator-associated pneumoniaB Eva Tejerina MDa, Fernando Frutos-Vivar MDa, Marcos I. Restrepo MDb, Antonio Anzueto MDb, Fekri Abroug MDc, Fernando Palizas MDd, Marco Gonza´lez MDe, Gabriel D’Empaire MDf, Carlos Apezteguı´a MDg, Andre´s Esteban MD, PhDa,* for the Internacional Mechanical Ventilation Study Group a

Intensive Care Unit, Hospital Universitario de Getafe, 28905-Getafe, Madrid, Spain Intensive Care Unit, South Texas Veterans Health Care System, University of Texas Health Science Center, San Antonio, TX, USA c Intensive Care Unit, Centre Hospitalo-Universitaire Fattouma Burghuiba, 5000 Monastir, Tunisia d Intensive Care Unit, Clinica Bazterrica, 1425 Buenos Aires, Argentina e Intensive Care Unit, Hospital General de Medellin, Medellin, Colombia f Intensive Care Unit, Hospital de Clinicas Caracas, Caracas, Venezuela g Intensive Care Unit, Hospital Nacional Profesor Alejandro Posadas, 1706 Haedo, Argentina b

Received 18 February 2005; revised 6 July 2005; accepted 30 August 2005

Keywords: Critical care; Epidemiology; Mechanical ventilation; Ventilator-associated pneumonia; Mortality; Outcome

Abstract Objective: The purpose of this study is to determine the incidence, risk factors, and outcome of ventilator-associated pneumonia (VAP). Design: Prospective cohort. Setting: Three hundred sixty-one intensive care units (ICUs) from 20 countries. Patients and Participants: Two thousand eight hundred ninety-seven patients mechanically ventilated for more than 12 hours. Measurements and Results: Baseline demographic data, primary indication for mechanical ventilation, daily ventilator settings, multiple organ failure over the course of mechanical ventilation, and outcome were collected. Ventilator-associated pneumonia was present in 439 patients (15%). Patients with VAP were more likely to have chronic pulmonary obstructive disease, aspiration, sepsis, and acute respiratory distress syndrome. Mortality in patients with VAP was 38%. Factors associated with mortality were severity of illness, limited activity before the onset of mechanical ventilation and development of shock, acute renal failure, and worsening of hypoxemia during the period of mechanical ventilation. Casecontrol analysis showed no increased mortality in patients with VAP (38.1% vs 37.9%, P = .95) but prolonged duration of mechanical ventilation and ICU stay.

B Grant 98/0233 from the Fondo de Investigacio´n Sanitaria, Spain. Red GIRA (G03/063) and Red RESPIRA (C03/11) from Instituto de Salud Carlos III, Spain. * Corresponding author. Intensive Care Unit, Hospital Universitario de Getafe, 28905-Getafe Madrid, Spain. Tel.: +34 916834982; fax: +34 916832095. E-mail address: [email protected] (A. Esteban).

0883-9441/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.jcrc.2005.08.005

Incidence, risk factors, and outcome of ventilator-associated pneumonia

57

Conclusion: In a large cohort of mechanically ventilated patients, VAP is more likely in patients with underlying lung disease (acute or chronic). Ventilator-associated pneumonia was associated with a significant increase in ICU length of stay but no increase in mortality. D 2006 Elsevier Inc. All rights reserved.

(c) neuromuscular disease; and (d) acute respiratory failure. The patients who fell in the category of acute respiratory failure were further divided into the following subgroups:

1. Introduction Ventilator-associated pneumonia (VAP) is an important complication in patients who need mechanical ventilation, and it has been reported to be the most common hospitalacquired infection in this cohort of patients [1]. In the past few years, several studies have reported the incidence of VAP and the risk factors related with its development and have assessed the impact of VAP on patient outcome [2-13]. Despite this vast literature, there are some discrepancies that are pending to be solved, especially those relative to attributable mortality of VAP. The objectives of our study are to estimate the incidence, the risks factors of VAP, and the attributable mortality of VAP in a large heterogeneous cohort of mechanically ventilated patients.

2. Methods 2.1. Study design We did a retrospective analysis of a database from a prospective, multicenter, international cohort of 5183 adult patients who received mechanical ventilation for more than 12 hours at 361 intensive care units (ICUs) from the March 1, 1998, to March 31, 1998, at 361 ICUs from 20 countries.

2.2. Patients We included in the study 2897 consecutive patients mechanically ventilated for more than 48 hours and whose reason for mechanical ventilation was not pneumonia. The following information were collected on each patient receiving mechanical ventilation: 1.

Variables at admission in the ICU—demographic data (sex, age, weight, date of admission to the ICU, Simplified Acute Physiology Score II [SAPS II] score at the time of ICU admission), type of problem (medical or surgical), day of initiating mechanical ventilation, and primary indication for mechanical ventilation that was selected from the following predefined list of categories: (a)

(b)

acute on chronic respiratory failure—exacerbation of chronic obstructive pulmonary disease (COPD), asthma, coma, neuromuscular or chronic respiratory disease, and chronic pulmonary disease other than COPD; coma;

(d.1)

acute respiratory distress syndrome (ARDS), (d.2) postoperative status, (d.3) acute pulmonary edema/congestive heart failure, (d.4) aspiration, (d.5) sepsis/septic shock, (d.6) trauma, and (d.7) cardiac arrest. 2.

Variables related to management—mode of ventilation, respiratory rate, tidal volume, applied positive end-expiratory pressure, need for vasoactive drugs, need for neuromuscular blockers, and arterial blood gas analysis. The arterial blood gases correspond to the values obtained once daily at approximately 8:00 am. The ventilator variables correspond to the time that the arterial blood gases were obtained. The use of neuromuscular blockers, sedatives, and vasoactive drugs (given for at least 3 hours in a 24-hour period) was recorded daily for a maximum of 28 days. 3. Variables related with the development of the following events during the course of mechanical ventilation—ARDS, barotrauma, sepsis, shock, renal failure, hepatic failure, coagulopathy, respiratory acidosis, and metabolic acidosis. Definitions: (a)

Barotrauma refers to the development of at least one of the following—interstitial emphysema, pneumothorax, pneumomediastinum, pneumoperitoneum, or subcutaneous emphysema. (b) Renal failure was defined as an acute increase in creatinine of more than 2 mg/dL (177 lmol/L), double the baseline value in a patient with underlying chronic renal failure, and/or the need for acute hemodialysis or acute use of any form of dialysis. (c) Hepatic failure was defined as an acute change in bilirubin to more than 2 mg/dL (34 lmol/L) with transaminase and lactic dehydrogenase levels at least twice the upper limit of normal. (d) Coagulopathy was defined as a decrease in the platelet count of 25% or more from the baseline with an increase in prothrombin time at least twice the control value.

58

E. Tejerina et al. (e) ( f)

Metabolic acidosis was defined as a pH less than 7.30 with a Paco2 less than 35 mm Hg. Respiratory acidosis was defined as a pH less than 7.35 with a Paco2 higher than 50 mm Hg. Sepsis and ARDS were considered as events only if they appeared more than 48 hours after mechanical ventilation was started. A patient was considered to have any of the abovementioned conditions if it was present for at least 2 consecutive days.

The appearance of VAP was registered daily. The diagnoses of VAP were defined according the modified Centers for Disease Control and Prevention criteria [14], which require a new radiographic infiltrate persistent for 48 hours or more plus a body temperature more than 38.58C or less than 35.08C, a leukocyte count of more than 10 000/lL or less than 3000/lL, a purulent sputum or change in character of sputum, or an isolation of pathogenic bacteria from endotracheal aspirate. We also distinguished between early-onset and late-onset VAP based on whether the diagnoses were done within the first 5 days of mechanical ventilation or after 6 or more days, respectively [15]. We performed these analyses to evaluate if the onset of diagnoses of VAP will have an impact in patient’s outcome.

2.3. Statistical analysis Results are expressed as means and SD, median with the interquartile range, and proportions as appropriate. We used the Student t test or the Mann-Whitney U test to compare continuous variables and the v 2 test to compare proportions. Two-tailed P values less than .05 were used to indicate statistical significance. To analyze the risk factors related to the development of VAP, we performed a univariate and a multivariate analysis with backward stepwise regression logistic analysis with the following variables: age, sex, previous functional status (normal or limited activity), SAPS II score, type of problem (medical or surgical), reason for mechanical ventilation, ARDS, and sepsis. Variables were entered in the model when P is less than .05. To evaluate the variables related to mortality in patients who developed VAP, we performed a univariate and a multivariate analysis with backward stepwise regression logistic analysis with the following variables: timing of the VAP (early onset or late onset); age (dichotomized taking as cutoff point 70 years [16]); sex; previous functional status (normal or limited activity); severity at admission based on SAPS II score (dichotomized taking as cutoff point for SAPS II of 45 points [16]); type of problem (medical or surgical); reason for mechanical ventilation; need of neuromuscular blockers; ventilator parameters (tidal volume, applied positive end-expiratory pressure, peak pressure, and plateau pressure—these variables were dichotomized using cutoff points that were clinically relevant with previously published threshold values); and complications appearing after the

diagnosis of VAP (barotrauma, ARDS, sepsis, shock, acute renal failure, hepatic failure, coagulopathy, metabolic acidosis, ratio of Pao2 to Fio2). Variables were entered in the model when P is less than .05. To determine the attributable mortality of VAP, we did a case-matched study [11]. We matched each patient with VAP with a control without VAP selected from the same cohort. The variables that we matched were previously identified by our group to be associated with mortality in mechanically ventilated patients [16]. The variables we matched were (a) parameters present at the beginning of mechanical ventilation (age, simplified acute physiologic score, and limited activity as previous functional status) and primary indication for mechanical ventilation (coma, ARDS, and sepsis); (b) variables related to patient management (use of vasoactive drugs, use of neuromuscular blockers, and plateau airway pressure higher than 35 cm H2O); and (c) variables occurring over the course of mechanical ventilation (development of barotrauma, ARDS, sepsis, shock, renal failure, hepatic failure, coagulopathy, metabolic acidosis, and ratio of Pao2 to Fio2). The variability range for matching age was F10 years, and for simplified acute physiologic score, F10 points. The attributable mortality was estimated as the Table 1

Characteristics of patients included in the study No VAP, VAP n = 2458 Early onset, Late onset, n = 363 n = 76

Age (y), mean (SD) 59 (17) 59 (17) Female, n (%) 946 (39) 121 (33) SAPS II, points, 44 (17) 44 (17) mean (SD) Previous functional status: 904 (37) 156 (43) limited activity, n (%) Problem, n (%) Medical 1589 (65) 272 (75) Surgical 869 (35) 91 (25) Main reason of mechanical ventilation, n (%) COPD 300 (12) 70 (19) Asthma 46 (2) 6 (2) Chronic pulmonary 41 (2) 7 (2) disease, not COPD Coma 506 (21) 73 (20) Neuromuscular disease 56 (2) 14 (4) Acute respiratory failure 1509 (61) 193 (53) Causes of acute respiratory failure, n (%) ARDS 170 (7) 24 (7) Postoperative 462 (19) 39 (10) Aspiration 53 (2) 21 (6) Sepsis 255 (10) 33 (9) Trauma 244 (10) 28 (8) Congestive heart failure 292 (12) 31 (9) Cardiac arrest 58 (2) 11 (3) Successful noninvasive 101 (4) 13 (3) ventilation Unsuccessful noninvasive 33 (1) 4 (1) ventilation

56 (18) 21 (28) 44 (16) 26(34)

50 (66) 26 (34) 7 (9) 1 (1) 1 (1) 17 (22) 3 (4) 47 (62) 7 (9) 5 (7) – 5 (7) 17 (23) 9 (12) 2 (3) 4 (5) 1 (1)

Incidence, risk factors, and outcome of ventilator-associated pneumonia Table 2

59

Factors associated with development of VAP Incidence of VAP, n (%)

Univariate analysis Odds ratio (95% CI)

Sex Female Male Problem Surgical Medical COPD Neuromuscular disease Postoperative acute respiratory failure Aspiration Sepsis (1) ARDS (1) Ventilation Successful noninvasive ventilation Invasive Failure noninvasive ventilation

Multivariate analysis P

Odds ratio (95% CI)

P

.02 142 (13) 293 (16)

1 1.3 (1.0-1.6) .004

b.001 117 (12) 322 (17) 77 (20) 17 (23) 44 (9) 21 (28) 305 (55) 379 (69)

1 1.5 (1.2-1.9) 1.51 (1.1-2.0) 1.7 (1.0-3.0) 0.5 (0.4-0.7) 2.3 (1.4-3.8) 19.9 (15.7-25.4) 88.0 (64.0-120.8)

5 (5) 417 (15) 17 (34)

.003 .05 b.001 b.001 b.001 b.001 b.001

1 3.6 (1.5-8.9) 9.5 (3.2-27.9)

1 1.8 (1.2-2.6) 3.9 (2.2-6.9)

3.8 (1.4-10.6) 14.0 (9.5-19.9) 68.8 (47.5-99.7)

b.001

.007 b.001 b.001 .05

1 4.4 (0.7-26.9) 11.6 (1.5-93.2)

These categories include patients with ARDS and sepsis both as a reason for mechanical ventilation and before the diagnosis of VAP.

proportion of the crude mortality that was attributable to VAP: [(crude mortalitycases crude mortalitycontrols)/crude mortalitycontrols] [11].

3. Results 3.1. Incidence of and risk factors for ventilator-associated pneumonia In the period of study, 439 patients (15%; 95% confidence interval [CI], 14%-16%) were diagnosed with Table 3

VAP. The crude incidence of VAP was 15 episodes per 1000 ventilator-days. From these, 363 patients (83%) had earlyonset pneumonia and 76 patients (17%) had late-onset pneumonia. The median time of onset of VAP was 4 days (interquartile range, 3-5). The characteristics of patients with VAP included in the study are shown in Table 1. We observed differences in the comparison between patients with early- and late-onset pneumonia, in COPD, and in aspiration (most early onset) and trauma (most late onset). Patients with early-onset pneumonia had a significantly shorter duration of mechan-

Factors associated with mortality in patients with VAP Mortality, n (%) Univariate analysis

Multivariate analysis

Odds ratio (95% CI) P Age N 70 y SAPS II N 45 points Previous functional status: limited activity Neuromuscular disease ARDS (1) Sepsis (1) Complications after VAP ARDS Sepsis Shock Acute renal failure Hepatic failure Coagulopathy Metabolic acidosis Pao2 to Fio2 ratio N200 150-200 b150 Applied positive end-expiratory pressure N 10 cm H2O

Odds ratio (95% CI) P

60/119 (50) 88/176 (50) 81/182 (44.5) 2/17 (12) 125/379 (33) 96/305 (31.5)

2.0 2.4 1.6 0.2 4.3 2.4

(1.3-3.1) (1.6-3.5) (1.1-2.4) (0.05-0.9) (2.4-7.8) (1.6-3.6)

b.001 b.001 .01 .02 b.001 b.001

26/52 (50) 76/141 (54) 64/108 (59) 60/101 (59) 17/24 (71) 33/53 (62) 7/9 (78)

1.7 2.7 3.3 3.2 4.3 3.1 5.9

(1.0-3.1) (1.8-4.1) (2.1-5.1) (2.0-5.3) (1.7-10.6) (1.7-5.7) (1.2-29.4)

61/215 (28) 37/108 (34) 67/113 (59) 13/21 (62)

1 1.3 (0.8-2.1) 3.7 (2.3-5.9) 2.8 (0.1-6.9)

.05 b.001 b.001 2.2 (1.3-3.8) b.001 2.3 (1.3-4.4) b.001 b.001 .01 b.001 1 2.4 (1.3-4.4) 2.6 (1.5-4.5) .02

2.2 (1.4-3.5) 1.9 (1.2-3.1)

.001 .005

3.7 (1.8-7.4) 1.8 (1.1-3.1)

b.001 .01

These categories include patients with ARDS and sepsis both as a reason for mechanical ventilation and before the diagnosis of VAP.

.003 .002

b.001

60

E. Tejerina et al.

ical ventilation than patients with late-onset pneumonia (median, 12 days [interquartile range, 7-18] vs 20 days [interquartile range: 13-31]; P b .001) and shorter ICU length of stay (median, 14 days [interquartile range, 9-23] vs 23 days [interquartile range, 15-37]; P b .001).

3.2. Outcome and factors related to mortality in patients who developed ventilator-associated pneumonia The mortality of patients who developed VAP was 38% (166 of 439 patients). Patients with early-onset pneumonia had a mortality of 36% (132 of 363 patients) vs a mortality of 45% (34 of 76 patients) in late-onset pneumonia ( P = .17). Table 2 shows the risk factors for VAP derived from univariate and multivariate analysis. The variables associated with mortality in patients developing VAP are displayed in Table 3. Nonsurvivors had a worse Pao2 to Fio2 ratio on the day of diagnosis (188 F 87 vs 213 F 90, P b .001) and during the follow-up period (Fig. 1).

3.3. Influence on outcome of ventilator-associated pneumonia (attributable mortality) Patients with VAP had significantly longer duration of mechanical ventilation [median 10 days (interquartile range, 5-16) vs 5 days (interquartile range, 3-7)] and of ICU length of stay [median, 14 days (interquartile range, 8-24) vs 8 days (interquartile range, 5-14), P b .001)] compared with patients without VAP. To estimate the attributable ICU mortality, we found controls without VAP for the 439 patients with VAP. The characteristics of VAP cases and controls are shown in Table 4. There was no statistically significant difference in hospital mortality among patients with or without VAP (38.1% vs 37.9%, P = .95). The relative risk attributable to VAP is 1.00 (95% CI, 0.84-1.18).

Fig. 1

Day after the diagnosis of ventilator associated pneumonia.

Table 4 Characteristics of patients with VAP and their matched controls Cases, n = 439 Age, mean (SD) 58 (17) SAPS II, mean (SD) 44 (16) Prior functional status: 42 limited activity (%) Reason for mechanical ventilation Coma (%) 20 Sepsis, % 8.7 ARDS (%) 7 Use of vasoactive drugs (%) 55 Use of neuromuscular 20 blockers (%) Plateau pressure 3 N 35 cm of water (%) Barotrauma (%) 5.7 ARDS (%) 13 Sepsis (%) 32 Shock (%) 32 Renal failure (%) 31 Hepatic failure (%) 9 Coagulopathy (%) 16 Metabolic acidosis (%) 4 Pao2 to Fio2 ratio (%) b100 2 100-150 13 150-200 36 200-300 26 N300 23

Controls, n = 439

P

58 (17) 45 (17) 37

.72 .51 .21

21 7.5 6 49 16

.80 .54 .59 .07 .13

4

.34

5.7 13 30 32 31.7 9 16 6

1.00 .84 .46 .88 .77 .90 .78 .16 .10

4 10 36 28 21

4. Discussion The main findings in this study are that in a large cohort of patients mechanically ventilated for more than 24 hours, VAP was diagnosed in 15% and was more likely to be present in patients with underlying lung diseases (ARDS and COPD), aspiration, and sepsis. The mortality of these patients was 38%, and the risk factors associated were the development of shock, the acute renal failure, and the worsening hypoxemia during the course of mechanical ventilation. Furthermore, the case-control analysis showed that patients with VAP had no increase in mortality but prolonged duration of mechanical ventilation and ICU stay. The incidence of VAP reported in the literature is widely variable and ranges from 10% to 65% [2-10]. This variability is mainly due to different diagnostic criteria and differences on the patient population included in these studies. This is mainly due to the lack of clinical and radiographic criteria that have high sensitivity and specificity values for the diagnoses of pneumonia in this patient population. A possible limitation of our study is the criteria used to diagnose pneumonia. In our study, we defined VAP based on the clinical criteria proposed by the Centers for

Incidence, risk factors, and outcome of ventilator-associated pneumonia Disease Control and Prevention [15]. At the time we designed this study, the clinical criteria used were the most commonly used criteria to identify VAP. The clinical pulmonary infection score (CPIS) has been considered to be more sensitive for the diagnosis of VAP, but in a recent publication, validating this score with lung biopsy, the CPIS was not superior to conventional clinical criteria [17]. Thus, we believe that in our study, we were able to identify most of the patients who developed this complication. Several risk factors have been identified in patients who developed VAP [18]. We identified that patients with chronic pulmonary obstructive disease, aspiration of gastric contents, ARDS, and sepsis as a precipitating cause of mechanical ventilation are the most common risk factors for VAP. These conditions were previously identified by other authors in single [2,7] and multicenter studies [3,6,9,19]. We also were able to identify that medical patients were more likely to develop pneumonia than surgical patients, contrary to the reports by Cunnion et al [9] and Garibaldi et al [20] that postsurgical patients are at high risk for VAP. The design of our study and the data analysis did not allow us to define the reasons for our findings. In this study, we wanted to evaluate the impact of VAP in the mortality rate. We observed a crude mortality of 38%. There were no significant differences according to the onset of pneumonia, although we observed a trend toward a higher mortality in the late-onset VAP patients. Previously published studies reported that VAP patients have ICU mortality rates between 24% and 76% [18]. To determine if VAP itself contributes to morbidity and mortality, we used a matched control analysis. Several reports in the literature have used similar matching procedures [4,5,8-12]. It is important to point out that these studies used different diagnostic procedures to diagnose VAP and wide diverse matching variables. The reported attributable mortality in VAP oscillates between 0% and 50%. We found in our study that VAP is not associated with increased mortality. We used a methodology similar to the report by Heyland et al [11] and obtained similar results. Furthermore, neither studies observed the association of onset of the pneumonia and mortality, contrary to the report by Ibrahim et al [21] who found that late-onset pneumonia was associated with increased mortality (hazard ratio, 1.53; 95% CI, 1.02-2.3). With respect to the impact of VAP on morbidity, we found significant differences between the cases and controls, including increased ICU and hospital length of stay, and in the patients with VAP. In our study, patients who developed VAP had longer duration of mechanical ventilation (5 days more) and ICU stay (6 days more). The prolongation of ICU stay as a direct consequence of VAP has been estimated in several studies and is summarized in the report by Chastre and Fagon [18]. However, it is difficult to determine if duration of mechanical ventilation could be a cause or an effect of VAP. Available data from several studies suggest that longer duration of mechanical ventilation is an adverse effect of VAP. Although, the cumulative risk for developing

61

VAP increases over time, the daily hazard rate for VAP decreases after day 7 [6,22]. There are a few studies that report risk factors for death of ventilated patients who developed pneumonia [23,24]. Using multiple logistic regression analysis, these authors have identified the following independent factors related to mortality: severity of underlying disease leading to ICU admission, severity of pneumonia itself, worsening respiratory failure, presence of an ultimately or rapidly fatal underlying concomitant condition, presence of shock, inappropriate antibiotic therapy, adequacy of initial antibiotic treatment, and type of ICU. In our study, we found some of the same factors as severity of illness at the admission to ICU, previous limited activity, development of shock, acute renal failure, and worsening of hypoxemia during the course of mechanical ventilation. In a similar pattern to that found by us, Luna et al [25] reported that the evolution of the ratio Pao2 to Fio2 was significantly different between survivors and nonsurvivors, and that improvement in this ratio was the best correlate of clinical response and outcome. A limitation of our study is that we did not collect any microbiology or treatment data. In conclusion, our study confirms that in a large cohort of mechanically ventilated patients, VAP is present in 15% of the patients during their course of ventilatory support and is closely related to the patients’ underlying medical condition and complications that develop over time. Our data demonstrate after controlling for confounding variables that VAP is not a risk factor for mortality. However, VAP prolongs duration of mechanical ventilation and ICU length of stay. Furthermore, prospective studies are warranted to further understand the impact in clinical outcomes of VAP.

Appendix A. The investigators for the International Mechanical Ventilation Study Group were ARGENTINA Coordinators: C Apezteguia, F Palizas. R Alasino (Hospital Municipal de Urgencias, Co´rdoba); R Bastianelli (Hospital Militar, Villa Revol); J Bero´n (Hospital Pablo Soria, San Salvador); C Bevilacqua (Clı´nica Modelo de Moro´ n, Moro´ n); M Cafaro (Hospital Regional Rı´o Gallegos, Rı´o Gallegos); E Capparelli (Hospital Eva Pero´n, San Martı´n); G Cardonatti (Hospital San Isidro, San Isidro); R Correa (Hospital Central, Mendoza); A Dı´ez (Hospital Provincial del Centenario, Rosario); E Estensoro (Hospital Escuela Jose´ de San Martı´n, La Plata); J Fara (Policlı´nico Ferroviario, Rosario); R Ferna´ndez (Hospital Italiano, Guaymalle´n); G Ferna´ndez Cid (Hospital E Tomu´, Buenos Aires); H Ferraro (Corporacio´n Me´dica de San Martı´n, San Martı´n); A Galaverna (Hospital Zonal Bariloche, Bariloche); C Galleti (Sanatorio Allende, Co´rdoba); G Garcı´a (Hospital Clemente ´ lvarez, Rosario); G Gelardi (Hospital Privado del Sur, Bahı´a A Blanca); S Giannasi (Hospital Italiano, Buenos Aires); R Guidi (Hospital Italiano Garibaldi, Rosario); L Huespe Gardel (Hospital Escuela Jose´ F de San Martı´n, Corrientes); C Irraza´bal (Hospital de

62 Clı´nicas Jose´ de San Martı´n, Buenos Aires); O Lo´pez (Sanatorio Santa Isabel, Buenos Aires); G Menga (Hospital Marı´a Ferrer, Buenos Aires); O Otero (Centro Oncolo´gico de Excelencia, Gonnet); F Pa´lizas (Clı´nica Bazterrica, Buenos Aires); P Pardo (Sanatorio de la Trinidad, Buenos Aires); C Plaza (Sanatorio Julio Me´ndez, Buenos Aires); G Raimondi (FLENI, Buenos Aires); A Raimondi (Sanatorio Mater Dei, Buenos Aires); E Romero (Hospital Privado Centro Me´dico, Co´rdoba); L de Rosa (Sanatorio Quintar, San Salvador); C Sa´ez (Sanatorio Brita´nico, Rosario); A Sarsino (Hospital Juan A Ferna´ndez, Buenos Aires); P Schoon (Hospital Prof Luis Gqemes, Haedo); C Sola (Hospital Jose´ Penna, Bahı´a Blanca); C Stfltzing (Hospital Guillermo Rawson, San Juan); J Taccone (Instituto Alfredo Lanari, Buenos Aires); C Tolosa (Hospital Co´rdoba, Co´rdoba); M Torreno (Sanatorio Modelo Quilmes, Quilmes); E Turchetto (Hospital Privado de la Comunidad, Mar de Plata); R Valenti (CEMIC, Buenos Aires); R Vargas (Policlı´nico Neuquen, Neuquen); L Vasta (Sanatorio San Patricio, Buenos Aires); L Va´zquez (Hospital Espan˜ol, Godoy Cruz); Vetere (Hospital Israelita Ezrah, Buenos Aires); F Villarejo (Hospital Prof Alejandro Posadas, Haedo); N Wainsztein (Hospital Privado Fundacio´n Favaloro, Buenos Aires); O Yunk (Hospital Espan˜ol, Buenos Aires); G Zabert (Clı´nica Pasteur, Neuquen). BOLIVIA Coordinator: F Sandi Lora. L Moya (Hospital Juan XXIII, La Paz); E Salazar (Hospital Japone´s, Santa Cruz); JC Zapata (Hospital Obrero, La Paz). BRAZIL Coordinator: CM David. SM Ajeje Lobo (Hosp de Base de Sa˜o Jose´ do Rio Preto, Sa˜o Jose´ do Rio Preto); AB de Almeida (Hospital das Clı´nicas da Univers Federal, Uberlaˆndia); MA Braga (Hospital Biocor, Belo Horizonte); I Buselato Chen (Hospital Nossa Senhora das Grac¸as, Curitiba); M Chaves Craveiro de Melo (Hospital Sa˜o Lucas, Belo Horizonte); RN Darwich (Hospital Prontocor, Belo Horizonte); CM David (Hospital Clementino Fraga Filho, Rio de Janeiro); R Goldstein Alheira Rocha (Hospital Samaritano, Sa˜o Paulo); R de Macedo Bosco (Hospital Madre Teresa, Belo Horizonte); JM Nogueira (Hospital Universitario Sa˜o Jose´ Belo Horizonte); E Oliveira (Hospital Vera Cruz, Belo Horizonte); SF Pinto (Casa de Sau´de Sa˜o Jose´, Campo Grande); SF Pinto (Santa Casa de Campo Grande, Campo Grande); SF Pinto (Univ Fed Mato Grosso do Sul, Campo Grande); JL da Rocha Paranhos (Santa Casa de Misericordia, Sa˜o Joa˜o del Rei); LR de Siqueira Musolino (Irmandade da Santa Casa de Misericordia, Sa˜o Paulo). CANADA Coordinator: TE Stewart. R Fowler (Wellesley-Central Hospital, Toronto); J Granton (Toronto Hospital General Division, Toronto); J Granton (Toronto Hospital Western Division, Toronto); R Hodder (Ottawa Civic Hospital, Ottawa); B Kashin (Peel Memorial Hospital, Brampton-Ontario); S Lapinsky (Mount Sinai Hospital, Toronto); D Mazer (St Michael’s Hospital, Toronto); R McLean (Sunnybrook Health Sciences Centre, Toronto); T Rogovein (St Joeseph’s Health Centre, Toronto). CHILE Coordinator: L Soto. G Buguedo (Hospital Pontificia Universidad Cato´lica, Santiago); P Herna´ndez (Instituto Nacional del To´rax, Santiago); C Ortega (Hospital Regional Concepcio´n, Concepcio´n); L Soto (Hospital de Coquimbo, Coquimbo); L Schflz (Hospital de Osorno, Osorno). COLOMBIA Coordinator: M Gonza´lez. H Atehortua (Clı´nica Sta Marı´a Centro Cardiovascular, Medellı´n); C Cadavid (Hospital Pablo

E. Tejerina et al. Tobo´n Uribe, Medellı´n); D Camargo (Hospital Universitario, Barranquilla); C Duen˜as (Hospital Universitario, Cartagena); A Guerra (Hospital General, Medellı´n); M Granados (Fundacio´n Valle de Lilly, Cali); R Panesso (Clı´nica Las Ame´ricas, Medellı´n); MA Perafa´n (Clı´nica Shaio, Bogota´). ECUADOR Coordinator: J Raad. B Guevara (Hospital Carlos Andrade, Quito); J Molina (Hospital Militar, Quito); J Raad (Hospital Militar, Quito). FRANCE Coordinator: L Brochard. P Andrivet (Centre Me´dico-Chirurgical de Bligny, Bris-sous-Forges); D Annane (Hoˆpital Raymond Poincare´, Garches); C Arich (CHU de Nimes, Nimes); F Baud (Hoˆpital Lariboisie`re, Paris); F Bellenfant (Hoˆpital Cochin, Paris); R Boiteau (Hoˆpital Louise Michel, Evry); F Brivet (Hoˆpital A Be´cle`re, Clamart); M Canonne (CHG Les Feugrais, Elbeuf); JP Cardinaud (Hoˆpital Pellegrin-Tripode, Bourdeaux); E Cle´menti (Centre Hosp Dept, La Roche/Yon); P Charbonneau (CHU Coˆte de Nacre, Caen); J Chastre (Hoˆpital Bichat, Paris); R Chauveau (CH Andre´ Gre´goire, Montreuil-Ss-Bois); C Chopin (CHRU-Hoˆpital B, Lille); JM Descamps (Centre Hospitalier de Niort, Niort); D Dreyfuss (Hoˆpital Louis Mourier, Colombes); JP Faller (C Hosp de Belfort, Belfort); F Fraisse (Hoˆpital Delafontaine, Saint-Denis); C Girault (Hoˆpital Charles Nicolle, Rouen); C Gue´rin (Hoˆpital Croix Rousse, Lyon); E Guerot (Hoˆpital Boucicaut, Paris); F Hilpert (Hoˆ pital Ballanger, Aulnay-sous-Bois); L Holzapfel (Centre Hospitalier, Bourg-en-Bresse); F Jardin (Hoˆpital Ambroise Pare´ , Boulogne Vignancourt); O Jonquet (Hoˆ pital Gui de Chauliac, Montpellier); E L’Her (CHU de la Cavale Blanche, Brest); Y Lefort (Hoˆpital Henri Mondor, Creteil); O Leroy (Centre Hospitalier, Tourcoing); Y Le Tulzo (CHU Pontchaillon, Rennes); Ch Mayaud (Hoˆpital Tenon, Paris); H Mentec (Hoˆpital Victor Dupouy, Argenteuil); A Mercat Hoˆpital Bice´tre, Kremlin-Bicetre); B Misset (Hoˆpital Saint-Joseph, Paris); P Moine (Hoˆpital Biceˆtre, Bicetre); G Nitemberg (IGR, Villejuif); L Papazian (Hoˆpital Sainte Marguerite, Marseille); A Rabbat (Hoˆpital Hoˆtel-Dieu, Paris); T Similowski (Hoˆpital Pitie´ Salpe´trie`re, Paris); L Soufir (Hoˆpital Saint-Louis, Paris); D Tardy (Hoˆpital Saint-Camille, Bry-surMarne); F Thaler (CM Chirurgical Foch, Suresnes); B Vallet (Centre Hospitalier Univ, Lille); D Villers (CHU Nantes, Nantes); M Wysocki (Institut Mutualiste Montsouris, Paris); JF Zazzo (Hoˆpital A Be´cle`re, Clamart). GREECE Coordinator: D Matamis. D Georgopoulus (Heraklion University Hospital, Heraklion); M Gianakou (Ahepa University Hospital, Thessaloniki); D Lagonidis (Papanikolaou Hospital, Thessaloniki); G Nakos (Ioanina University Hospital, Ioanina); K Stavrakaki (Evangelismos Hospital, Athens); G Thomopoulus (Laikon Hospital, Athens). IRELAND Coordinator: G Fitzpatrick. M Donnelly (Adelaide and Meath Hospital, Dublin); J Moriarty (St James Hospital, Dublin); B O’Sullivan (Waterford Regional Hospital, Waterford); G Shorten (Cork University Hospital, Cork). ITALY Coordinator: P Pelosi. Cositi (Pol Umberto I, Roma); G Iapichino (Hospital S Paolo, Milan); P Pelosi (Policlı´nico, Milan); A Pesenti (Dsp S Gerardo, Monza). MEXICO Coordinator: J Elizalde. F Aguilera Almaza´n (Hospital General Regional No 1, Chihuahua); M Benitez Cortazar (Hospital

Incidence, risk factors, and outcome of ventilator-associated pneumonia Universitario de Puebla, Puebla); R Carrillo Speare (Hospital PEMEX Sur, Me´xico DF); R Castan˜o (Hospital de Cardiologı´a del CMN, Me´xico DF); R Corral (Hospital Excel Tijuana, Baja California); DM D’Ector Lira (Hospital Metropolitano, Me´xico DF); G Dı´az Polanco (Hospital de Traumatologı´a Magdalena de las Salinas, Me´xico DF); JJ Elizalde (Hospital ABC, Me´xico DF); R Envila Fisher (Hospital Morelos, Chihuahua); R Envila Fisher (Hospital Clı´nica del Parque, Chihuahua); G Franco G (Hospital General de Me´xico, Me´xico DF); P Garcı´a Balbuena (Hospital General bFernando Quiroz,Q Me´ xico DF); O Gayoso Cruz (Hospital Regional bAdolfo Lo´pez Mateos,Q Me´xico DF); L Green (Instituto Nacional de Cancerologı´a, Me´xico DF); JO Herrera Hoyos (Centro Me´dico Las Ame´ricas, Me´rida); J Hinojosa (Hospital Angel Lean˜o, Guadalajara); J Huerta (Clı´nica Londres, Me´xico DF); VA Jua´rez (Hospital Santelena, Me´xico DF); M Loera (Hospital General Durango, Durango); C Lo´pez Alzate (Clı´nica del Mar, Mazatla´n); E Lo´pez Mora (Instituto Nacional de Cardiologı´a, Me´xico DF); S Martı´nez Cano (Hospital Hidalgo Aguascalientes, Aguascalientes); R Mendez Reyes (Hospital Regional 18 de Octubre, Me´xico DF); M Mendoza (Hospital General de la Villa, Me´xico DF); O Narva´ez Porras (Instituto Nacional de Enfermedades Respiratorias, Me´xico DF); E Ortiz (Hospital General Irapuata, Guanajuato); A Padua (Hospital General Torreo´n, Coahuila); M Poblano (Hospital Jua´rez, Me´xico DF); V Pureco Reyes (Hospital Regional b20 de Noviembre,Q Me´xico DF); W Querevalum (Hospital Central Cruz Mexicana, Me´xico DF); A Quesada (Hospital Ntra Sra de la Salud, San Luis Potosı´); A Ramı´rez Rivera (Hospital de Enfermedades Cardiovasculares y del To´rax IMSS, Monterrey); A Tamariz (Hospital Clı´nica del Centro, Chihuahua); A Tamariz (Hospital Central Universitario, Chihuahua); A Vargas (Hospital General de Pachuca, Pachuca); C Va´zquez (Hospital General Celaya, Guanajuato). PERU Coordinator: AM Montan˜ez. M Contardo (Edgardo Rebagliati Martins-UCI 78B, Lima); E Durand (Guillermo Almenara IrigoyenIPPS, Lima); M Manrique (Hospital bJose Casimiro Ulloa,Q Lima); JC Meza (Centro Me´ dico Naval, Lima); J Mun˜oz (Edgardo Rebagliati Martins—UCI 28C, Lima); J Pacheco (Hospital del Apoyo bMarı´a Auxiliadora,Q Lima); C Salcedo (Hosp Nacional bDaniel Alcides Carrio´n,Q Lima); J Silva (Hospital Central FAP, Lima); C Torres (Hospital Nacional bArzobispo Loayza,Q Lima). PORTUGAL Coordinator: J Pimentel. P Amaro (Centro Hospitalario de Gaia, Gaia); F Faria (Instituto Portugue´s de Oncologı´a, Porto); P Freitas (Hospital Fernando da Fonseca, Amadora-Sintra); P Martins (Hospital Universidade, Coimbra); E Sabino (Hospital Garcı´a de Orta, Almada); J Salcher (Hospital de San Jose´ UUM, Lisboa); E Silva (Hospital Senhora do Desterro, Lisboa). SPAIN Coordinators: A Esteban, F Frutos-Vivar. JM Allegre (Hospital Nuestra Sen˜ora del Rosell, Cartagena); S Alonso (Hospital Joan XXIII, Tarragona); A Alvarez Ruiz (Hospital General Rio Carrio´n, Palencia); B Alvarez Sa´nchez (Hospital General, Alicante); MT Antuna (Hospital de Cabuen˜es, Gijo´n); JM An˜o´n (Hospital Virgen de la Luz, Cuenca); P Arribas (Hospital 12 de Octubre, Madrid); A Ayensa (Hospital Virgen de la Salud, Toledo); A Azca´rate (Hospital Nuestra Sen˜ora de Aranzazu, Donostia); J Blanco (Hospital del Rı´o Hortega, Valladolid); GM Besso (Hospital Carlos Haya, Ma´laga); L Cabre´ (Hospital de Barcelona, Barcelona); F Carrizosa (Hospital General, Je´rez de la Frontera); J Castan˜eda (Hospital Clı´nico, Valladolid); R de Celis (Hospital de Galdakao,

63

Galdakao); JA Conesa (Hospital Clı´nico Universitario San Carlos, Madrid); J Diarte (Complejo Hospitalario, Ciudad Real); A Dı´az Lamas (Complejo Hospitalario Cristal Pin˜or, Orense); R Ferna´ndez (Consorci Hospitalari del Parc Taulı´, Sabadell); M Ferrer (Hospital Clinic i Provincial, Barcelona); D Fontaneda (Hospital Virgen Blanca, Leo´n); P Galdo´s (Hospital General, Mo´stoles); A Garcı´a Jime´nez (Hospital Arquitecto Marcide, El Ferrol); J Garcı´a Pardo (Hospital Juan Canalejo, La Corun˜a); J Gener (Hospital Germans Trias i Pujol, Badalona); JA Go´mez Rubı´ (Hospital Virgen de la Arrixaca, Murcia); G Gonza´lez Dı´az (Hospital Morales Meseguer, Murcia); S Gonza´lez Prado (Hospital Josep Trueta, Girona); C Homs (Hospital General San Jorge, Huesca); J Iban˜ez (Hospital Son Dureta, Palma de Mallorca); F Jara (Hospital Mutua, Terrassa); M Leo´n (Hospital Arnau de Vilanova, Lleida); A Lloria (Complejo Hospitalario Rebullo´n, Pontevedra); J Lo´pez Dı´az (Hospital La Paz, Madrid); MaR Lorenzo (Complejo Hospitalario Materno-Infantil, Las Palmas de Gran Canaria); S Macı´as (Hospital General, Segovia); JA Maldonado (Hospital de la Serranı´a, Ronda); J Maynar (Hospital Santiago Apostol, Vitoria); A Moreno (Complejo Hospitalario de San Milla´n-San Pedro, Logron˜o); A Mota (Hospital General Universitario, Elche); T Mut (Hospital General, Castello´n); M Nolla (Hospital General de Catalun˜a, Sant Cugat del Valle´s); F Ortega (Hospital Universitario de Valme, Sevilla); R de Pablo (Hospital Prı´ncipe de Asturias, Alcala´ de Henares); E Palazo´n (Hospital General Universitario, Murcia); V Parra (Hospital de Sagunto, Sagunto); A Peral (Hospital Gregorio Maran˜o´n, Madrid); JC Portela (Complejo Hospitalario XeralCalde, Lugo); A Ramı´rez (Hospital Nuestra Sen˜ora de Sonsoles, Avila); JA Ramos (Hospital de Poniente, El Ejido); P Revuelta (Hospital Universitario de Canarias, La Laguna); M Rey (Complejo Hospitalario, Santiago de Compostela); JJ Rodrigo (Hospital Nuestra Sen˜ora del Pino, Las Palmas de Gran Canaria); JC Rodrı´guez Borregan (Hospital Marque´s de Valdecilla, Santander); JA Rodrı´guez Sarria (Hospital General, Elda); A Rubio (Hospital Ramo´n y Cajal, Madrid); S Ruiz Navarro (Hospital General Ciudad de Jaen, Jaen); V Sagredo (Hospital Virgen de la Vega, Salamanca); P Saura (Centre Hospitalari, Manresa); MJ Serralta (Hospital Universitario de San Juan, Alicante); JF Solsona (Hospital del Mar, Barcelona); F Sua´rez Sipmann (Fundacio´n Jime´nez Dı´az, Madrid); F Taboada (Hospital General de Asturias, Oviedo); S Temprano (Hospital Severo Ochoa, Legane´s); JP Tirapu (Hospital de Navarra, Pamplona); MaV de la Torre (Hospital Universitario Virgen de la Victoria, Ma´laga); P Ugarte (Hospital Marque´s de Valdecilla, Santander); M Valledor (Hospital de San Agustı´n, Avile´s); I Vallverdu´ (Hospital de la Santa Creu i Sant Pau, Barcelona); C Vaquerizo (Hospital 12 de Octubre, Madrid); A Vin˜uales (Hospital Lluis Alcanyis, Xa´tiva). TUNISIA Coordinator: F Abroug. A Bchiz (Hospital F Bached, Sousse); J Ben Khelil (Hospital A Mami, Ariana); S Bern Lakhal (Hospital Rabta, Tunis); B Bouhaja (Hospital Mongi Slim, La Marsa); H Chelly (Hospital Fattouma Bourguiba, Sfax); S El Atrous (Hospital Fattouma Bourguiba, Monastir); S Ghedira (Hospital Charles Nicolle, Tunis); H Thabet (CAMUR Tunis). UNITED KINGDOM Coordinator: P Nightingale. O Akinpelu (Chorley and District Hospital, Chorley); D Bardgett (Macclesfield District General Hospital, Macclesfield); A Batchelor (Royal Victoria Infirmary, Newcastle upon Tyne); R Beale (Guy’s Hospital, London); K Burchett (Queen Elizabeth Hospital, King’s Lynn); N Coleman (North Staffordshire Royal Infirmary, Stoke on Trent); A Conn

64 (Wansbeck General Hospital, Ashington); D Edbrooke (Royal Hallamshire Hospital, Sheffield); N Fergusson (Countess of Chester Hospital, Chester); I Grant (Rotherham District Hospital, Rotherham); K Gunning (Addenbrooke’s Hospital, Cambridge); J Harper (Royal Liverpool University Hospital, Liverpool); D Higgins (Southend Hospital, Westcliffe-on-Sea); D Jayson (Southport and Formby General Hospital, Southport); R Loveland (Wexham Park Hospital, Slough); L Lynch (Birmingham Heartlands Hospital, Birmingham); I Macartney (North Manchester General Hospital, Manchester); E Major (Morriston Hospital, Swansea); S Mousdale (Blackbum Royal Infimary, Blackburn); N Soni (Chelsea and Westminster Hospital, London); D Watson (Walsgrave Hospital, Walsgrave). URUGUAY Coordinator: C Rodrigo. H Bagnulo (Maciel, Montevideo); C Rodrigo (Asociacio´n Espan˜ola Primera, Montevideo); M Rodrı´guez (Hospital de Paysandu´, Montevideo). USA Coordinator: A Anzueto. SM Aguayo (Atlanta VA Medical Center, Decatur); R Alagar (Allegheny General Hospital, Pittsburgh); RK Albert (Denver Health Medical Center, Denver); TK Aldrich (Montefiore Hospital and Medical Center, Bronx); K Amoosa (Medical College of Wisconsin, Milwaukee); N Anandarao (New York Methodist Hospital, Brooklyn); DC Angus (University of Pittsburg, Pittsburgh); AC Arroliga (Cleveland Clinic Foundation, Cleveland); MF Azrieli (Jacobu Medical Center, Bronx); RA Balk (Medical Center—203 Jelke, Chicago); PW Bates (Maine Medical Center, Porthland); JF Beamis, Jr (Lahey Hitchcock Medical Center, Burlington); PE Bellamis (Chs Dept of Medicine, Los Angeles); DJ Bower (Atlanta VA Medical Center, Decatur); JP Bradley (William Beaumont Medical Center, El Paso); RP Byrd, Jr (University of East Tennese, Jonesboro); VJ Cardenas, Jr (University of Texas Medical Branch, Galveston); LJ Caruso (University of Florida, Gainesville); BR Celli (St Elizabeths Medical Center, Boston); G Clermon (University of Pittsburg, Pittsburgh); SJ Coole (Carl T Hayden VA Medical Center, Phoenix); TA Dillard (Commander MCHJ-MPU, Tacoma); LE Efferen (SUNY Health Science Center, Brooklyn); EW Ely, Jr (Vanderbilt Lung Transplant Program Newline, Nashville); P Factor (Michael Reese Hospital and Medical Center, Chicago); TM Fitzpatrick (Walter Reed Army Medical Ctr, Whashington); R Fowler (Wellesley-Central, Toronto); GN Giacooppe, Jr (MCHJMPU, Tacoma); KK Guntupalli (Texas Med Ctr—Ben Taub Gen Hospital, Houston); JB Hall (University of Chicago, Chicago); ME Hanley (Denver Medical Center, Denver); MT Haupt (Oregon Health Science University, Portland); GB Hayes (St Elizabeths Medical Center, Boston); DE Heiselman (Akron General Medical Center, Akron); FC Hiller (University of Arkansas Med Science, Little Rock); JD Hinze (The Univesity of Texas Health Science Center at San Antonio, San Antonio); RD Hite (Bowman Gray School of Medicine, Winston-Salem); RC Hyzy (Henry Ford Hospital, Detroit); A Jubran (Edward Hines VA Hospital, Hines); CA Kaplan (University of Missouri Columbia, Columbia); MS Karetzky (Newark Beth Israel Med Ctr, Newark); SA Kurenhy (Truman Medical Center, Kansas); KV Leeper, Jr (Emory University School of Medicine, Atlanta); H Levy (University of New Mexico, Alburquerque); T Lo (Loma Linda University, Loma Linda); MJ Mador (Buffalo VA Medical Center, Bu´falo); GP Marelich (University of California Davis Med Ctr, Sacramento); MA Matthay (University of California, San Francisco); NR McIntyre (Duke University Medical Center, Durham); SA Metter

E. Tejerina et al. (Maine Medical Center, Portland); MS Niederman (Winthrop Univesity Hospital, Mineola); JR Norman (Univesity of Mississippi Medical Center, Jackson); DR Oullette (Brooke Army Medical Center, Fort Sam Houston); P Parsons (Denver Medical Cente, rDenver); RG Patel (VA Medical Center, Jackson); RC Perkins II (University of Texas Health Center at Tyler, Tyler); ME Petrini (University of Miississippi Medical Center, Jackson); MR Pinsky (University of Pittsburg, Pittsburgh); A Pohlman (Edward Hines VA Hospital, Hines); KW Presberg (Medical College of Wisconsin, Milwaukee); MP Rocha (Carl T Hayden VA Medical Center, Phoenix); W Rodrı´guez Cintron (San Juan VA Medical Center, San Juan); MJ Rosen (Beth Israel Medical Center, New York); TM Roy (James Quillen College of Medicine, Mountain Home); G Rudelfeld (Harborview Medical Center, Seattle); MJ Rumbak (University Florida, Tampa); SJ Ruoss (Stanford University Medical Center, Stanford); GA Schmidt (University of Chicago, Chicago); RF Schneider (Beth Israel Medical Center, New York); CN Sessler (Medical College of Virginia, Richmond); CS Shim (Jacobi Medical Center, Bronx); L Smith (RushPresbyterian-St Lukes Medical Center, Chicago); C Strange (MUSC 96 Jonathan Lucas St, Charleston); JI Sznajder (Michel Reese Hospital and Medical Center, Chicago); S Tessler (Maimonides Medical Center, Brooklyn); V Whyte (Loma Linda University, Loma Linda); L Wilkelmeyer (Loma Linda University Medical Center MC 1521, Loma Linda); RG Wundering (501 Crews Wing, Memphis); MH Zaman (The Brookdale Hosp Med Ctr, Brooklyn); LH Zimmerman (San Francisco VA Medical Center, San Francisco). VENEZUELA Coordinator: GDEmpaire. J Espan˜a (Hospital Universitario, Caracas); F Pe´rez (Hospital de Clı´nicas, Caracas); R Zerpa (Hospital Militar, Caracas).

References [1] Vincent JL, Bihari DJ, Suter PM, et al. The prevalence of nosocomial infection in intensive care units in Europe. Results of the European prevalence of infection in intensive care (EPIC) study. EPIC International Advisory Committee. JAMA 1995;274:639 - 644. [2] Torres A, Aznar R, Gatell JM, et al. Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am Rev Respir Dis 1990;142:523 - 8. [3] Rello J, Quintana E, Ausina V, et al. Incidence, etiology, and outcome of nosocomial pneumonia in mechanically ventilated patients. Chest 1991;100:439 - 44. [4] Kappstein I, Schulgen G, Beyer U, Geiger K, Schumacher M, Daschner FD. Prolongation of hospital stay and extra costs due to ventilator-associated pneumonia in an intensive care unit. Eur J Clin Microbiol Infect Dis 1992;11:504 - 8. [5] Fagon JY, Chastre J, Hance AJ, Montravers P, Novara A, Gibert C. Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay. Am J Med 1993;94:281 - 8. [6] Chevret S, Hemmer M, Carlet J, Langer M. Incidence and risk factors of pneumonia acquired in intensive care units. Results from a multicenter prospective study on 996 patients. Intensive Care Med 1993;19:256 - 64. [7] Fagon JY, Chastre J, Vuagnat A, Trouillet JL, Novara A, Gibert C. Nosocomial pneumonia and mortality among patients in intensive care units. JAMA 1996;275:866 - 9. [8] Baker AM, Meredith JW, Haponik EF. Pneumonia in intubated trauma patients. Microbiology and outcomes. Am J Respir Crit Care Med 1996;153:343 - 9.

Incidence, risk factors, and outcome of ventilator-associated pneumonia [9] Cunnion KM, Weber DJ, Broadhead WE, Hanson LC, Pieper CF, Rutala WA. Risk factors for nosocomial pneumonia comparing adult critical-care populations. Am J Respir Crit Care Med 1996;153: 158 - 62. [10] Papazian L, Bregeon F, Thirion X, et al. Effect of ventilator-associated pneumonia on mortality and morbidity. Am J Respir Crit Care Med 1996;154:91 - 7. [11] Heyland DK, Cook DJ, Griffith L, Keenan SP, Brun-Buisson C. The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient. Am J Respir Crit Care Med 1999;158:1249 - 56. [12] Bercault N, Boulain T. Mortality rate attributable to ventilatorassociated nosocomial pneumonia in an adult intensive care unit: a prospective case-control study. Crit Care Med 2001;29:2303 - 9. [13] Rello J, Ollendorf DA, Oster G, et al. Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest 2002;122:2115 - 21. [14] CDC definitions for nosocomial infections, 1988. Am Rev Respir Dis 1989;139:1058 - 9. [15] American Thoracic Society. Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventive strategies. Am J Respir Crit Care Med 1996;153: 1711 - 25. [16] Esteban A, Anzueto A, Frutos F, et al. Characteristics and outcomes in adult patients receiving mechanical ventilation. A 28-day international study. JAMA 2002;287:345 - 55.

65

[17] Fabregas N, Ewig S, Torres A, et al. Clinical diagnosis of ventilator associated pneumonia revisited: comparative validation using immediate post-mortem lung biopsies. Thorax 1999;54:867 - 73. [18] Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med 2002;165:867 - 903. [19] Cook DJ, Walter SD, Cook RJ, et al. Incidence and risk factors for ventilator-associated pneumonia in critically ill patients. Ann Intern Med 1998;129:433 - 40. [20] Garibaldi RA, Britt MR, Coleman ML, Reading JC, Pace NL. Risk factors for postoperative pneumonia. Am J Med 1981;70:677 - 80. [21] Ibrahim EH, Ward S, Sherman G, Kollef MH. A comparative analysis of patients with early-onset vs. late-onset nosocomial pneumonia in the ICU setting. Chest 2000;117:1434 - 42. [22] Moine P, Timsit JF, de Lassence A, et al. Mortality-associated with late-onset pneumonia in the intensive care unit: results of a multicenter cohort study. Intensive Care Med 2002;28:154 - 63. [23] Celis R, Torres A, Gatell JM, Almela M, Rodriguez-Roisin R, AgustiVidal A. Nosocomial pneumonia. A multivariate analysis of risk and prognosis. Chest 1988;93:318 - 24. [24] Torres A, Aznar R, Gatell JM, et al. Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am Rev Respir Dis 1990;142:523 - 8. [25] Luna CM, Blanzaco D, Niederman MS, et al. Resolution of ventilatorassociated pneumonia: prospective evaluation of the clinical pulmonary infection score as an early clinical predictor of outcome. Crit Care Med 2003;31:676 - 82.