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(Chest. 2005;127:1353-1357.)
© 2005 American College of Chest Physicians

Stable Patients Receiving Prolonged Mechanical Ventilation Have a High Alveolar Burden of Bacteria*

Daniel Baram, MD, FCCP; Geoffrey Hulse, MD and Lucy B. Palmer, MD, FCCP

* From the Division of Pulmonary/Critical Care Medicine, Stony Brook University, Stony Brook, NY.

Correspondence to: Daniel Baram, MD, FCCP, Assistant Professor of Medicine, Division of Pulmonary/Critical Care Medicine, T-17 Room 040 HSC, Stony Brook University, Stony Brook, NY 11794-8172; e-mail: dbaram{at}notes.cc.sunysb.edu


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 References
 
Introduction: In patients receiving prolonged mechanical ventilation (PMV), quantitative bronchoscopic culture has not been validated for the diagnosis of ventilator-associated pneumonia (VAP).

Objective: To measure the alveolar burden of bacteria in patients receiving PMV.

Setting: Respiratory care units of a university hospital and a long-term care facility.

Patients: Fourteen patients requiring PMV without clinical evidence of pneumonia.

Measurements: Quantitative culture of BAL from the right middle lobe and lingula.

Results: In 29 of 32 lobes, there was growth of at least one organism at > 104 cfu/mL. Most lobes had polymicrobial growth.

Conclusions: Stable patients receiving PMV without clinical pneumonia have a high alveolar burden of bacteria. The bacterial burden in most patients exceeds the commonly accepted threshold for diagnosing VAP. The utility of quantitative bronchoscopic culture in the diagnosis of VAP in this patient population requires further study.

Key Words: BAL • colony count • laboratory diagnosis • long-term care • mechanical ventilation • microbial pneumonia


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusions
 References
 
Ventilator-associated pneumonia (VAP) is the second most frequent nosocomial infection in the ICU and is associated with the highest morbidity and cost.1 Clinical criteria for diagnosing VAP are unreliable.2 Quantitative bronchoscopic culture is recommended as a tool for increasing diagnostic certainty, as the burden of bacteria in the distal airspaces correlates with histologic evidence of VAP.34 Further, use of an invasive diagnostic strategy has been shown to decrease mortality in patients with suspected VAP.5

In patients with acute respiratory failure, bacterial growth of > 104 cfu/mL on quantitative BAL is evidence for VAP.6 The sensitivity of quantitative BAL for the diagnosis of VAP ranges from 42 to 93% with a mean of 73%, and the specificity ranges from 45 to 100% with a mean of 82%.7 In patients receiving mechanical ventilation up to 60 days, the specificity of quantitative culture for VAP decreases with the duration of mechanical ventilation.68 The accuracy of BAL culture for diagnosing pneumonia in patients receiving mechanical ventilation for > 60 days is unknown. We performed quantitative BAL culture to determine the bacterial burden in the alveoli of patients receiving prolonged mechanical ventilation (PMV) without clinical evidence of pneumonia.


   Materials and Methods
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 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusions
 References
 
Patients for this study were recruited from the Respiratory Care Unit of University Hospital at Stony Brook and the Respiratory Care Unit of the Gurwin Geriatric Center, a long-term care facility (LTCF). Fourteen patients receiving PMV with no evidence of clinical pneumonia were identified. Each patient was afebrile, had a normal leukocyte count, had stable chest radiograph findings, and was receiving continual mechanical ventilation via a tracheostomy tube. No patient had received antibiotics for at least 7 days prior to bronchoscopy. Patients requiring clinical bronchoscopy were excluded. All patients in both facilities were screened during two periods separated by 10 months. Patients meeting criteria were approached for consent. Two patients in the LTCF met enrollment criteria in both screening periods and underwent a second bronchoscopy. The protocol was approved by the institutional review board of both facilities. Each patient or representative gave informed consent.

Demographic data were collected, including age, duration of ventilator dependence, and cause of respiratory failure. Patients were designated as having "no swallowing dysfunction" if they passed formal swallowing evaluation and were allowed oral feedings; patients were designated as having "swallowing dysfunction" if they failed formal swallowing testing and received nutrition via a gastrostomy tube or had refused gastrostomy tube feeding.

Quantitative BAL was performed of the right middle lobe (RML) and lingula using standard technique. The bronchoscope was rapidly positioned into the RML and tightly wedged in place. Sixty milliliters of sterile normal saline solution were instilled, and the aspirate was discarded. Without loss of the wedged position, another 60 mL were instilled, and the aspirated fluid was collected in a sterile container. The procedure was repeated in the lingula, and the sample was collected in a separate container. Samples obtained at the university hospital were immediately delivered to the microbiology laboratory for processing. Samples obtained at the LTCF were transported to the microbiology laboratory on ice.

All patients were followed up for 2 weeks for the development of VAP based on the following clinical criteria: (1) onset of fever, (2) leukocytosis, (3) change in the character or purulence of the sputum, and/or (4) change on radiograph. Patients in the LTCF continued to be followed up for the development of symptomatic respiratory infection, as defined by receiving antibiotics or requiring admission to an acute care hospital. Symptomatic respiratory infections were designated as tracheobronchitis if the patient was systemically well, had no significant change on chest radiography, but had symptoms such as increased need for suctioning or desaturation related to secretions and responded to oral or aerosolized antibiotics. Symptomatic respiratory infections were designated VAP if the patient was febrile, had new infiltrates, and/or required IV antibiotics. Bronchoscopic culture specimens were not obtained during episodes of respiratory infection, and the distinction between tracheobronchitis and VAP was determined by the treating clinician. Data are presented as mean ± SD.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusions
 References
 
Patient demographics and the primary cause of respiratory failure are listed in Table 1 . Mean patient age was 62 ± 13 years. The duration of mechanical ventilation at the time of enrollment into the study was 33 ± 45 months, with a median duration of 20 months. No patients had complications from the procedure. Microbiologic data are presented in Table 2 . Of the 32 BAL cultures sent, 29 cultures (91%) had bacterial growth > 104 cfu/mL. The lobes had 1.8 ± 1.0 bacterial species with > 104 cfu/mL of growth.


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  		Table 1.. Demographics*

 

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  		Table 2.. Microbiologic Result

 
Table 3 presents the clinical outcomes of the patients. Only one patient acquired clinical VAP or received antibiotics in the 2-week follow-up period. Of the patients in the LTCF, three died and the nine remaining patients continue to require ventilatory support. In 183 ventilator-months of follow-up, there were 16 bouts of respiratory infection: 9 infections were clinical VAP and 7 were clinically diagnosed as tracheobronchitis. No patients required admission to an acute care hospital for VAP, and each bout of VAP was treated with IV antibiotics. Three of the seven tracheobronchitis cases were treated with aerosolized antibiotics; four patients received oral antibiotics. There were nine episodes of VAP per 5,490 ventilator-days, for an incidence of 0.002 per ventilator-day. In patients with symptomatic infection, the time from bronchoscopy to the first bout of respiratory infection was 5.5 ± 4.8 months.


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  		Table 3.. Clinical Outcome

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusions
 References
 
Patients receiving PMV for chronic respiratory failure were found to have a high burden of bacteria within the distal airspaces at a time when there was no clinical evidence of VAP. Despite this high burden of bacteria, VAP developed in only one patient within 2 weeks of bronchoscopy. In patients who did have clinical respiratory infection during prolonged follow-up, treatment was not required for 5.5 ± 4.8 months.

This study adds to our understanding of airway colonization in patients with a tracheostomy. Colonization of the bronchial tree occurs early in the course of mechanical ventilation; by the seventh day, most patients have colonization.9 Sterilization of the bronchial secretions is unlikely as long as the trachea remains cannulated. In 39 patients with tracheostomy living at home, of whom only 1 required mechanical ventilation, the tracheal colonization rate was 83%, and 30% of protected specimen brush culture results were positive. Overall, 46% of patients received antibiotics for respiratory tract infection. There were five bouts of pneumonia reported, as defined by the criteria of "signs and symptoms of LRTI [lower respiratory tract infection] and a new infiltrate on chest radiograph," yielding a pneumonia rate of 10 per 100 person-years.10 In a study of 14 hospitalized patients11 with a tracheostomy for > 3 months, of whom 12 patients required PMV, quantitative tracheal secretion culture had a mean of 106.9 cfu/mL. Distal airway sampling was not performed.

To our knowledge, ours is the first study of distal airway cultures in patients with tracheostomy requiring PMV. Our data suggest that patients with tracheostomy requiring PMV have a higher bacterial burden and a higher rate of VAP than patients with tracheostomy living at home.

There were > 11,000 patients receiving PMV in the United States in 1990.12 Many of these patients have purulent secretions and persistent radiographic abnormalities making the diagnosis of VAP difficult. In our study, despite a low daily incidence of 0.002 VAP per ventilator-day, 43% of patients acquired VAP from 1 to 11 months after the BAL. In a series13 of 199 patients in a long-term acute care hospital, 50% died in the facility and 19% required readmission to an acute-care hospital. The attributable morbidity and mortality of VAP was not reported. One study14 found VAP to be a major cause of mortality in this patient population, and another study15 reported the incidence of VAP as being 50 to 66%.

The pathogenesis of VAP is not fully understood. VAP usually occurs after bacterial colonization of the trachea. The incidence of VAP is highest in the first 2 weeks of ventilation.161718 In one large study,16 VAP had a peak daily incidence of 3% on day 5; VAP rates then decreased to a mean daily incidence of 1% by day 15. The daily incidence of VAP in this study is considerably lower than that reported in patients with acute respiratory failure.

A high bacterial burden in distal airspaces correlates with the presence of VAP in autopsy tissue in studies3419 of patients with acute respiratory failure. Interestingly, in patients with left-sided infiltrates, nondirected sampling of distal airways also correlates with the presence of VAP.20 This suggests that a high alveolar bacterial burden is a marker for VAP, not that more bacteria are present in pneumonic lobes or that lobes containing a high burden of bacteria have pneumonia.

The bacterial species causing VAP varies among hospitals and likely depends on patient factors, endemic flora, and antibiotic utilization.21 The high prevalence of methicillin-resistant Staphylococcus aureus and Pseudomonas in this study is in keeping with the endemic flora of our institutions.

Corynebacterium and non-ß-hemolytic Streptococcus, so-called oropharyngeal or cutaneous commensal microorganisms (OCC), accounted for 20% (11 of 54) of the isolates in this study. Interestingly, all patients with OCC had swallowing dysfunction. In a large retrospective study,22 patients with significant quantitative growth of OCC followed a clinical course typical of VAP, and it was recommended that OCC should be considered pathogenic. In that study, 10% of VAP were caused by OCC.

In this study, 63% of the cultures had polymicrobial growth. In one retrospective study,23 48% of VAP cases were polymicrobial, and the overall outcome and epidemiology of polymicrobial VAP did not differ from patients with monomicrobial VAP.

Quantitative distal culture as a means of differentiating airway colonization and pneumonia has been best validated in patients with acute respiratory failure and in patients experiencing their first pulmonary infection. In one study,6 patients receiving mechanical ventilation for > 14 days were more likely to have discrepant results between BAL culture and the clinical diagnosis of pneumonia than those receiving mechanical ventilation for < 14 days. Discrepant results were also more common in subsequent pneumonias than during the first bout of pneumonia. In another study,8 patients with a longer duration of ventilation were more likely to have nonsterile protected specimen brush cultures than patients with shorter ventilation. Patients in this study were receiving mechanical ventilation considerably longer than patients reported in these studies, and likely experienced multiple bouts of prior pneumonia.

Our study shows that patients receiving PMV have a low daily incidence of VAP despite a high burden of pathogenic bacteria. Patients with chronic respiratory failure appear better able to control a high alveolar burden of bacteria and acquire VAP less commonly than do acutely ill patients with respiratory failure. It has been suggested that patients surviving to require PMV may be a select group able to resist the development and impact of VAP.15 The mechanism of controlling the high bacterial burden is unknown and worthy of further study. Despite this low daily incidence, patients receiving PMV have multiple bouts of symptomatic respiratory infection over the course of their illness.

This study has clinical import. If one of our patients receiving PMV were to become septic and undergo diagnostic bronchoscopy, quantitative BAL culture would likely demonstrate bacterial growth at > 104 cfu/mL and VAP would be considered microbiologically proven. Other sources of infection might be overlooked.

The 104 cfu/mL cutoff for the diagnosis of VAP appears unreliable in patients requiring PMV, as the majority of BAL cultures in our study exceeded this level of growth in the absence of clinical infection and most patients followed a benign clinical course for several months without treatment. The distinction between colonization, tracheobronchitis, and VAP is difficult in these patients. Further study is required to determine if quantitative culture has any role in the diagnosis of VAP in this population.


   Conclusions
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
References
 
Patients requiring PMV have a large burden of bacteria in their distal airspaces, frequently exceeding the levels diagnostic for VAP in patients with acute respiratory failure. Despite the high burden of bacteria, these patients have a low daily incidence of VAP. Further study is needed to determine the pathogenesis and incidence of VAP in patients with chronic respiratory failure and to determine if quantitative bronchoscopic culture has a role in the diagnosis of VAP in these patients.


   Footnotes
 
Abbreviations: LTCF = long-term care facility; OCC = oropharyngeal or cutaneous commensal microorganisms; PMV = prolonged mechanical ventilation; RML = right middle lobe; VAP = ventilator-associated pneumonia

Received for publication January 14, 2004. Accepted for publication October 6, 2004.


   References
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 References
 

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