CHEST Original ResearchCRITICAL CARE

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Ventilator-associated pneumonia (VAP) is common in intubated patients and is associated with increased

morbidity, mortality, and health-care costs. 1,2 Ventilator-associated tracheobronchitis (VAT) has been pro-posed as an intermediate condition between simple colonization of the upper airways and VAP 3,4 and has

been reported to occur in 2.7% 5 to 10.6% 6 of intubated patients. Treatment of VAT with antibiotics has been proposed as a means to decrease subsequent progres-sion to VAP and to improve outcomes. 3 Two small

Background: Ventilator-associated tracheobronchitis (VAT) is considered an intermediate condi-tion between bacterial airway colonization and ventilator-associated pneumonia (VAP). The pur-pose of this prospective cohort study was to further characterize VAT in terms of incidence, etiology, and impact on patient outcomes. Methods: Patients intubated for . 48 h in the surgical and medical ICUs of Barnes-Jewish Hospital were screened daily for the development of VAT and VAP over 1 year. Patients were followed until hospital discharge or death, and patient demographics, causative pathogens, and clinical outcomes were recorded. Results: A total of 28 patients with VAT and 83 with VAP were identifi ed corresponding to fre-quencies of 1.4% and 4.0%, respectively. VAP was more common in surgical than medical ICU patients (5.3% vs 2.3%; P , .001), but the occurrence of VAT was similar between surgical and medical patients (1.3% vs 1.5%; P 5 .845). VAT progressed to VAP in nine patients (32.1%) despite antibiotic therapy. There was no signifi cant difference in hospital mortality between patients with VAP and VAT (19.3% vs 21.4%; P 5 .789). VAT was caused by a multidrug-resistant (MDR) patho-gen in nine cases (32.1%). Conclusion: VAT occurs less commonly than VAP but at a similar incidence in medical and surgical ICU patients. VAT frequently progressed to VAP, and patients diagnosed with VAT had similar outcomes to those diagnosed with VAP, suggesting that antimicrobial therapy is appropriate for VAT. VAT is also frequently caused by MDR organisms, and this should be taken into account when choosing antimicrobial therapy. CHEST 2011; 139(3):513–518

Abbreviations: APACHE 5 Acute Physiology and Chronic Health Evaluation; cfu 5 colony forming units; CPIS 5 Clinical Pulmonary Infection Score; ETA 5 endotracheal tube aspirate; MDR 5 multidrug resistant; VAP 5 ventilator-associated pneumonia; VAT 5 ventilator-associated tracheobronchitis

Ventilator-Associated Tracheobronchitis in a Mixed Surgical and Medical ICU Population John Dallas , MD ; Lee Skrupky , PharmD ; Nurelign Abebe , MD ; Walter A. Boyle III , MD ; and Marin H. Kollef , MD, FCCP

Manuscript received June 2, 2010; revision accepted July 27, 2010. Affi liations: From the Department of Pulmonary and Critical Care Medicine (Drs Dallas and Kollef ), and the Departments of Anesthesiology and Surgery (Dr Boyle), Washington University School of Medicine; the Department of Pharmacy (Dr Skrupky), Barnes-Jewish Hospital; and the Department of Internal Medicine (Dr Abebe), St. Luke’s Hospital, St. Louis, MO. Funding/Support: This study was supported in part by the Barnes-Jewish Hospital Foundation. Correspondence to: Marin H. Kollef, MD, FCCP, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8052, St. Louis, MO 63110; e-mail: mkollef@dom.wustl.edu

© 2011 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians ( http://www.chestpubs.org/site/misc/reprints.xhtml ). DOI: 10.1378/chest.10-1336

For editorial comment see page 485

randomized clinical trials 7,8 evaluating the effi cacy of such treatment showed positive effects, including lower rates of subsequent VAP and decreased dura-tion of mechanical ventilation. Unfortunately, few pro-spective studies have been published that directly

514 Original Research

96 h after initial diagnosis of VAT. In order to be included in this grouping, patients had to display continued evidence of ongoing infection as evidenced by temperature . 38.3°C, temperature , 36.0°C, or leukocyte count . 12,000/ m L. If a new organism associated with VAP was isolated from the respiratory cultures of a patient previously diagnosed with VAT, then they were judged not to have progressed from VAT to VAP. These patients were instead considered to have a new distinct episode of VAP, which was not included in the analysis. Subsequent distinct epi-sodes of VAT or VAP occurring more than 96 h following the initial episode of VAT or VAP were also not included in this analysis.

Defi nitions of VAT and VAP

VAT was defi ned as the presence of all of the following in a patient endotracheally intubated and receiving mechanical venti-lation for . 48 h: body temperature . 38.3°C or , 36.0°C, new or increased purulent tracheal secretions, positive culture of tracheal secretions at a concentration of � 10 5 cfu/mL, and no new or pro-gressive infi ltrate on portable chest radiograph. VAP was defi ned as the presence of a new or progressive pulmonary infi ltrate and two of the following: temperature . 38.3°C or , 36.0°C, leukocyte count . 12,000/ m L or , 4,000/ m L, or purulent tracheal secretions. The diagnosis of VAP was considered to be microbio-logically confi rmed if either BAL or ETA cultures had signifi cant growth. The presence or absence of a new or progressive radio-graphic infi ltrate was based on the interpretation of the chest radiograph by board-certifi ed radiologists who were blinded to the study. All classifi cations, including the radiographs and labo-ratory data used in their determinations, were prospectively reviewed by one of the investigators (J. D.) and confi rmed by a second investigator (M. H. K.). Culture-negative cases of VAP were defi ned as cases meeting all the clinical criteria for VAP but with nonsignifi cant ETA or BAL cultures in the presence of newly started antibiotics within 48 h of culture sampling.

Microbiology Methods

ETAs were only obtained when there was suspicion of either VAT or VAP. Specimens were obtained by respiratory therapist or nurses using a deep tracheal suctioning technique to obtain a specimen for culture. All ETAs and BAL cultures were processed using quantitative methods as previously described. 14 The tubes containing the respiratory specimens were fi rst vortexed for 15 s. A 0.01-mL calibrated loop was placed into the respective speci-mens and then onto the center of three media plates (blood agar, chocolate agar, and MacConkey agar). The media plates were then streaked using the pinwheel streak method and incubated in CO 2 at 35°C. Bacterial culture growth was quantitated accord-ing to the number of colonies observed per plate: , 10 colonies per plate represented , 10 3 cfu/mL; 10 to 100 colonies per plate represented 10 3 to 10 4 cfu/mL; 100 to 1,000 colonies per plate represented 10 4 to 10 5 cfu/mL; and . 1,000 colonies per plate represented . 10 5 cfu/mL. All identifi ed microorganisms were reported with their antibiotic sensitivities.

Statistical Analysis

All comparisons were unpaired, and all tests of signifi cance were two-tailed. Continuous variables were compared using the Student t test for normally distributed variables and the Mann-Whitney U test for nonnormally distributed variables. The x 2 or Fisher exact tests were used to compare categorical variables. For all analyses, a two-tailed P value , .05 was considered statisti-cally signifi cant. Statistical analyses were performed using SPSS, Version 11.0 for Windows (SPSS, Inc; Chicago, Illinois).

evaluate VAT and controversies concerning diagnostic criteria and true distinction from VAP exist. 3,9 The contention that VAT is associated with adverse out-comes, such as increased lengths of stay, has been refuted by some studies, 10 and increased mortality with the diagnosis has not been established. 11 Therefore, given the paucity of North American data concerning VAT, we set out to perform a prospective cohort study of VAT in ICU patients to determine its incidence and infl uence on patient outcomes compared with VAP.

Materials and Methods

Study Population and Data Collection

The study was conducted in the surgical (24 beds) and medical (19 beds) ICUs of Barnes-Jewish Hospital, a 1,200-bed urban teach-ing hospital in St. Louis, Missouri. During the course of 365 days, beginning on January 19, 2009, the ICU patient rosters were screened daily. Patients mechanically ventilated for . 48 h were monitored daily for the development of either VAT or VAP. The Washington University Human Research Protection Offi ce reviewed and approved the research protocol (HRPO number 08-1233).

Patients who met the prospectively defi ned defi nitions of VAP and VAT during the study period were included in the analysis unless they met one of the following exclusion criteria: presence of another ongoing nosocomial infection requiring antimicrobial treatment, presence of a tracheostomy at the time of VAT or VAP suspicion, signifi cant immune suppression defi ned as prolonged neutropenia ( . 1 week), HIV-positive with an absolute CD4 cell count , 50/ m L during the preceding 6 months, or chronic steroid therapy at a dosage � 40 mg of prednisolone daily for a duration of . 4 weeks.

The following baseline characteristics were recorded at the time of VAT or VAP diagnosis: age, sex, race, height, weight, maxi-mum body temperature in the previous 24 h, leukocyte count, quantity and character of pulmonary secretions, presence of comorbid conditions, modified Clinical Pulmonary Infection Score (CPIS), 12 APACHE (Acute Physiology and Chronic Health Evaluation) II 13 score at ICU admission, ratio of Pa o 2 to F io 2 , and the causative organism(s) associated with VAT and VAP. Respira-tory secretions were sent for microbiologic analysis only at times of suspected infection, and there was no routine surveillance of respiratory cultures performed during the study period.

Endotracheal tube aspirates (ETAs) were considered positive if � 10 5 colony-forming units (cfu)/mL were identifi ed. BAL sam-ples were considered positive at � 10 4 cfu/mL. Causative patho-gens were considered multidrug resistant (MDR) if they were resistant to two or more of the primary antibiotics used to treat nosocomial pneumonia at our hospital (cefepime, piperacillin-tazobactam, meropenem).

Secretion volume and character are routinely recorded every 8 h by nurses and respiratory therapists caring for intubated patients. Secretion volume is graded on the following scale: none, scant, small ( , 30 mL/d), moderate (30-100 mL/d), or large ( . 100 mL/d). Patients who were diagnosed with VAT or VAP were followed until hospital discharge or death and the following parameters were recorded: duration of mechanical ventilation, duration of ICU stay, duration of hospitalization, requirement for tracheostomy, total days of antibiotic usage in the ICU, and days of antibiotics used for treatment of the episode of VAT or VAP that led to study enrollment.

Some patients were judged to progress from VAT to VAP based on development of a new or progressive infi ltrate in the

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qualifying for the diagnosis of VAP as determined by the investigators. There was no statistically signifi -cant difference in baseline medical comorbidities or APACHE II scores between the VAT and VAP groups. The CPIS score was signifi cantly greater in the VAP group compared with patients with VAT at the time of infection diagnosis. The distribution of VAT and VAP relative to intubation and the start of mechani-cal ventilation is shown in Figure 1 . The mean onset of VAT was 8.3 6 4.8 days (median 7.5 days; inter-quartile range, 5.25-10.0 days), and the mean onset of VAP was 6.7 6 4.1 days ( P 5 .052) (median 5.0 days; interquartile range, 4.0-8.0 days).

Incidence of VAT and VAP

The incidences of VAT and VAP are shown in Table 2 . Among patients intubated for . 48 h, the overall inci-dence of VAT was 1.4%, and the overall incidence of VAP was 4.0%. This corresponds to a rate of 3.2 cases of VAT per 1,000 mechanical ventilator days and a rate of 9.4 cases of VAP per 1,000 mechanical ventil-ator days. The incidence of VAP was signifi cantly greater than the incidence of VAT ( P , .001). There was no statistically significant difference in the incidence of VAT in medical ICU patients (1.5%) when compared with the incidence of VAT in surgical ICU patients (1.3%). VAP occurred at a greater inci-dence in surgical ICU patients (5.3%) than in medical ICU patients (2.3%), P , .001.

VAT progressed to VAP in nine patients (32.1%) despite concurrent therapy with appropriate anti-biotics that were predicted to be effective based on in vitro susceptibility testing of the VAT causative organ-isms in all nine patients. There was no statistical dif-ference in the overall rate of appropriate initial antibiotic therapy in the VAT group (71.4%) as com-pared with the VAP group (71.1%).

Microbiology

Causative pathogens of VAT and VAP are shown in Table 3 . VAT was caused by an MDR pathogen in nine (32.1%) patients and was polymicrobial in seven (25.0%) patients. VAP was caused by an MDR pathogen in 31 (37.3%) patients and was polymicro-bial in 16 (19.3%) patients. Gram-positive organisms accounted for 37.5% of the pathogens isolated in patients with VAT and 27.8% of the pathogens iso-lated in patients with VAP. Overall, there was no sig-nifi cant difference among the individual causative bacterial pathogens for patients with VAT compared with patients with VAP. However, Enterobacteriaceae were more commonly associated with VAP compared with VAT (31 of 90 [34.4%] vs 4 of 32 [12.5%]; P 5 .022).

Results

Patient Characteristics

During the course of 1 year, 2,060 patients admitted to the medical and surgical ICUs required mechanical ventilation for . 48 h. Among these patients, 111 patients (5.4%) were identifi ed as having either VAT or VAP. The baseline characteristics of the patients are shown in Table 1 . There were 28 (25.2%) patients with VAT and 83 (74.8%) patients with VAP. Twenty-two (78.6%) of the patients with VAT had moderate or large secretion volume, whereas six (21.4%) had small secretion volume recorded during the 24-h period when the diagnosis of VAT occurred. Either ETA or BAL fl uid was culture positive in 73/83 (88.0%) of the VAP cases (39 with BAL and 34 with ETAs). In the 10 (12.0%) patients with culture-negative VAP, all 10 received new antibiotics within 48 h of having respi-ratory samples obtained for culture.

Among patients with VAP, 41 (49.4%) had radio-graphic infi ltrates present prior to the diagnosis of VAP attributed to ARDS, pulmonary edema, atelectasis, or aspiration. All 41 of these patients had new infi l-trates or progression of their preexisting infi ltrates

Table 1— Patient Characteristics

Characteristic VAT (n 5 28 ) VAP (n 5 83) P Value

Age, y 56.1 6 15.6 50.4 6 17.2 .145Male sex 14 (50.0) 48 (57.8) .471Race White 20 (71.4) 41 (49.4) .043 Black 8 (28.6) 42 (50.6) .043ICU type Medical 13 (46.4) 20 (24.1) .025 Surgical 15 (53.6) 63 (75.9) .025BMI, kg/m 2 33.4 6 15.6 29.8 6 8.5 .566APACHE II at ICU admission

25.0 6 7.9 23.4 6 8.2 .271

CPIS at diagnosis of VAT/VAP

5.0 6 2.1 6.6 6 1.6 , .001

Prior antibiotic therapy 17 (60.7) 44 (53.0) .479Postoperative 11 (39.3) 45 (54.2) .172Trauma 5 (17.9) 27 (32.5) .138Appropriate antibiotic therapy a

20 (71.4) 59 (71.1) .584

Medical comorbidities COPD 7 (25.0) 10 (12.0) .100 Congestive heart failure 4 (14.3) 9 (10.8) .624 Diabetes 4 (14.3) 25 (30.1) .099 End-stage renal disease 3 (10.7) 6 (7.2) .559 Cirrhosis 1 (3.6) 3 (3.6) .992 Active malignancy 4 (14.3) 13 (15.6) .861 Morbid obesity b 5 (17.9) 6 (7.2) .104

Values expressed as mean 6 SD or No. (%). APACHE 5 Acute Phys-iology and Chronic Health Evaluation; CPIS 5 Clinical Pulmonary Infection Score; VAP 5 ventilator-associated pneumonia; VAT 5 ventilator-associated tracheobronchitis. a Defi ned as an initial antibiotic regimen with in vitro activity demon-strated against the causative pathogens. b Defi ned as a BMI . 40 kg/m 2 .

516 Original Research

Nseir et al 6 published the only study that prospec-tively evaluated the incidence of VAT based on the criteria that are most accepted currently. This inves-tigation was performed in a French teaching hospital, included medical and surgical ICU patients, and reported an overall incidence of VAT of 10.6%. Surgical patients were more likely than medical patients to develop VAT (15.3% vs 9.9%). In our study a signifi cantly lower overall incidence of VAT (1.4%) was noted and the incidence of VAT was similar in surgical and medical ICU patients.

Several potential factors may have contributed to the lower incidence of VAT reported in our study compared with the French study. Nseir et al 6 reported a high incidence of COPD (58%) in their population compared with our study (15%). Patients with COPD might be diagnosed more frequently with VAT as they are more likely to produce larger quantities of puru-lent secretions and may be more likely to have bacte-rial colonization of their upper airways. Additionally, endotracheal aspirates were only sent for culture in our study when there was a clinical suspicion for the presence of VAT or VAP. Nseir et al 6 reported that aspirates were routinely sent on admission and weekly thereafter in addition to at times of suspicion of infec-tion. The presence of more positive cultures might lead to an increased incidence of VAT in equivocal cases.

In our study, 32.1% of patients initially diagnosed with VAT evolved to fulfi ll VAP criteria. This per-centage is higher than that reported by Nseir et al 6 (9.0% of patients). However, in the subsequent ran-domized trial 8 of antibiotic therapy for VAT per-formed by these same investigators, 34% of patients with VAT developed subsequent VAP, but only three of 22 (13.6%) of these cases occurred in the group of patients who received antibiotics. These data suggest that the administration of antimicrobial therapy to patients with VAT may be an important factor infl u-encing whether VAT progresses to VAP. However, our study suggests that such progression can still occur in some patients despite the presence of appro-priate initial antimicrobial therapy for VAT.

VAT is believed to be a precursor or intermediate condition progressing to VAP. 3 The lower incidence of VAT compared with VAP and the more delayed onset of VAT compared with VAP that we observed are at odds with this hypothesis and suggest that VAT is not necessarily a precursor of VAP. One potential explanation for this deviation from the hypothesis that VAT should precede VAP is the difference in diagnostic criteria used to defi ne these infections. The diagnosis of VAT required a quantitative culture, whereas the diagnosis of VAP did not. Thus, intu-bated patients with purulent secretions that are cul-ture negative would be excluded from the VAT group.

Patient Outcomes

Outcomes of patients diagnosed with VAT and VAP are depicted in Table 4 . There was no signifi cant dif-ference in ICU or hospital length of stay, duration of mechanical ventilation, hospital mortality, tracheos-tomy, or antibiotic use between the VAT and VAP groups. When the nine patients with VAT who subse-quently developed VAP are removed from the analy-sis, there still are no signifi cant differences between the VAT and VAP groups for any of the outcomes measured.

Discussion

To our knowledge, this is the fi rst and largest pro-spective study of VAT from North America. A recent meta-analysis 11 reviewing VAT identifi ed only fi ve reports 6,10,15-17 deemed eligible for determining the incidence of VAT. The overall frequency of VAT was 11.5% based on these reports. However, most of these studies are limited by not being prospectively designed to evaluate VAT, 10,15-17 not using the standard defi nition of VAT, 10,15-17 and being conducted in very limited patient populations (head injury, 16 post car-diac surgery, 10 tertiary peritonitis 15 ).

Figure 1. Occurrence of ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) relative to the onset of tracheal intubation and mechanical ventilation. The days postintubation represent the number of calendar days following intubation that the patient developed either VAP or VAT.

Table 2— Incidence of VAT and VAP

Incidence VAT (n 5 28) VAP (n 5 83) P Value

Overall 3.2 9.4 , .001Medical ICU 3.1 4.8 .289Surgical ICU 3.2 13.6 , .001

Values expressed as incidence per 1,000 mechanical ventilator days. See Table 1 for expansion of abbreviations.

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that we observed and could potentially explain the onset of VAT at a later time point. Additionally, VAT and VAP could be mutually exclusive, rather than steps in the progression of a single infection, when alveolar host defenses are adequate at a time when airway defenses are overwhelmed.

Several important limitations of our study should be noted. First, there was potential for substantial overlap between patients with VAT and those with VAP based on the defi nitions we used. The absence of new or progressive infi ltrates observed on portable chest radiographs was the main differentiator between VAT and VAP. Given the nonspecifi city of radio-graphic fi ndings for VAP, 9 as well as the lack of sensi-tivity for portable chest radiographs to identify new infi ltrates, we cannot be certain that all our patients with VAP actually had pneumonia or that some of our patients with VAT did not actually have VAP. The overall similarity in median time to onset of VAT and VAP also suggests that there is considerable overlap between these two infections. Additionally, we required the same organism to be present in patients with VAT who progressed to VAP. Because we used quantita-tive culture methods, it is possible that we may have missed pathogens in low quantities that were present at the time of VAT and subsequently not associated with VAP. The second major limitation of our study is that we only examined patients with active infections, comparing those with VAT to those with VAP. There-fore, we cannot estimate the attributable mortality from VAT in our population. However, the lack of outcome differences between patients with VAT and those with VAP suggests that the attributable outcomes associated with VAT are similar to those of VAP. Third, as noted above, we cannot with certainty exclude the possibility that some of our patients with VAT were misclassifi ed because we did not routinely perform CT scans searching for occult infi ltrates. Fourth, we only obtained respiratory samples for culture when patients fulfi lled the clinical criteria suggesting the presence of either VAT or VAP. This may have resulted in an underestimation of the occurrence of VAT.

Another limitation of our study is that we measured CPIS scores in all patients, although the CPIS was originally developed for use in patients with VAP. 12 Although the CPIS scores were signifi cantly greater in patients with VAP compared with patients with VAT, there was overlap in the scores between them. This suggests that CPIS may be a poor diagnostic tool for VAP or that some of the patients with VAT may have actually had VAP. Similarly, 41 patients with VAP had infi ltrates present prior to establishing the diagnosis of VAP. Therefore, it is possible that some of these patients developed VAT and not VAP given the prior presence of infi ltrates. We also observed that the duration of antibiotic therapy for VAT was similar

This did not appear to be the case in our study, as we did not identify any patients with culture-negative purulent respiratory secretions who otherwise met the clinical criteria for VAT. An alternative explana-tion for the observed deviation is that VAT is not a precursor of VAP but that these are two distinct enti-ties that can arise from the noninfected state and can either coexist or exist separately. Such a model could account for the higher incidence of VAP over VAT

Table 3— Microbiology

OrganismVAT Pathogens

(n 5 32)VAP Pathogens

(n 5 90)

MDR pathogen 9 (28.1) 31 (34.4)Gram positive 12 (37.5) 25 (27.8) MRSA 6 (18.8) 10 (11.1) MSSA 4 (12.5) 9 (10.0) Streptococcus pneumoniae 2 (6.3) 5 (5.6) “Non-pneumococcal” Streptococci

2 (6.3) 7 (7.8)

Corynebacterium striatum 1 (3.1) 0 (0.0)Gram negative 16 (50.0) 58 (64.4) Acinetobacter baumannii 5 (15.6) 10 (11.1) Pseudomonas aeruginosa 3 (9.4) 11 (12.2) Haemophilus infl uenza 3 (9.4) 3 (3.3) Stenotrophomonas maltophilia 2 (6.3) 2 (2.2) Klebsiella pneumonia 1 (3.1) 6 (6.7) Enterobacter aerogenes 1 (3.1) 6 (6.7) Proteus mirabilis 1 (3.1) 3 (3.3) Serratia odoriferae 1 (3.1) 0 (0.0) Haemophilus parainfl uenza 0 (0.0) 1 (1.1) Enterobacter cloacae 0 (0.0) 6 (6.7) Citrobacter freundii 0 (0.0) 1 (1.1) Citrobacter koseri 0 (0.0) 2 (2.2) Escherichia coli 0 (0.0) 3 (3.3) Serratia marcescens 0 (0.0) 4 (4.4) Moraxella catarrhalis 0 (0.0) 1 (1.1) Polymicrobial infections a 7 (25.0) 16 (19.3)

Values expressed as No. (%). P . .05 for all comparisons. Among the nine patients with VAT that progressed to VAP, five were caused by MRSA, three by Pseudomonas aeruginosa , and one by Klebsiella pneumonia. MDR 5 multidrug resistant; MRSA 5 methicillin-resistant Staphylococcus aureus ; MSSA 5 methicillin-sensitive Staphylococcus aureus . See Table 1 for expansion of other abbreviations. a Based on actual number of patients with VAT and VAP.

Table 4— Outcomes Associated With the Diagnosis of VAT and VAP

Outcome VAT (n 5 28) VAP (n 5 83) P Value

ICU days 17.3 6 11.0 17.5 6 10.1 .711Hospital days 26.6 6 16.7 26.6 6 17.3 .919Mechanical ventilator days 16.5 6 13.3 15.1 6 10.0 .886Survive to discharge 22 (78.6) 67 (80.7) .789Required tracheostomy 13 (46.4) 46 (55.4) .512Total ICU antibiotic days 17.1 6 10.0 19.6 6 14.2 .699Antibiotic days for VAP

and VAT14.0 6 8.2 15.0 6 7.9 .719

Values expressed as mean 6 SD or No. (%). See Table 1 for expansion of abbreviations.

518 Original Research

companies/organizations whose products or services may be dis-cussed in this article.

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to that for patients with VAP. This also supports the possibility that the patients with VAT may actually have had VAP that was not clinically identifi ed. We also did not perform any sensitivity analyses for our defi nition of VAT. For example, if we eliminated the requirement for either hyperthermia or hypothermia then a larger group of patients would have met the criteria for VAT. This could have increased the likeli-hood of identifying patients with VAT that preceded VAP. However, we did not identify any patient who was treated with antibiotics for VAT without the temperature criteria or the purulent secretion crite-ria. Additionally, loosening the diagnostic criteria for VAT, without demonstrating any outcome benefi t in doing so, has the potential to increase antibiotic use, which could further drive increases in antimicrobial resistance. Finally, cultures for nonbacterial patho-gens, such as viruses and fungi, were not routinely performed on the ETA or BAL samples. Therefore, other potential pathogens may have been present, accounting for the fi ndings in some patients.

In conclusion, we demonstrated a signifi cantly lower rate of VAT than previously reported. 6 How-ever, we identifi ed patients with VAT that did prog-ress to VAP, and patients diagnosed with VAT had similar outcomes to those with VAP. VAT does not appear to be a necessary precursor for VAP. This does not negate the role of upper airway colonization in the pathogenesis of VAP. Indeed, local and systemic host factors, bacterial virulence properties, and ther-apeutic interventions may infl uence whether upper airway colonization progresses to clinically recog-nizable VAP. Further studies are needed to identify patients with VAT who would benefi t the most from antimicrobial therapy and those who could safely have antimicrobial therapy withheld or limited. Addi-tionally, the optimal duration of antimicrobial therapy and route of therapy (parenteral, aerosolized) needs to be determined for VAT.

Acknowledgments Author contributions : Drs Dallas and Kollef had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Dr Dallas: contributed to the study concept and design, statistical analysis, and the drafting of the manuscript. Dr Skrupky: contributed to the study concept and design, the analysis and interpretation of data, and the drafting of the manu-script and critical revision for important intellectual content. Dr Abebe: contributed to the study concept and design, formation of the study database, and critical revision of the manuscript for important intellectual content. Dr Boyle: contributed to the study concept and design, the analysis and interpretation of data, and critical revision of the manuscript for important intellectual content. Dr Kollef: contributed to the study concept and design and manu-script review. Financial/nonfi nancial disclosures: The authors have reported to CHEST that no potential confl icts of interest exist with any