Ventilator-Associated Pneumonia Therapy: Protected Specimen Brushing Versus Tracheal Aspirate Data

 

Curtis Peery, MD

Akella Chendrasekhar, MD

Donald W. Moorman, MD

Gregory A Timberlake, MD

 

Departments of Surgery Education and Trauma

Iowa Methodist Medical Center

Des Moines, IA

 

KEY WORDS: ventilator associated pneumonia, therapy, protected specimen brush

 

ABSTRACT

Study Objectives: Several studies on ventilator-associated pneumonia (VAP) have shown improved accuracy of diagnosis using quantitative deep tissue cultures verses nonquantitative tracheal aspirate (TA) cultures. We examined the clinical efficacy of treatment based on a more accurate diagnostic approach.

Design/Setting: Prospective randomized trial at a level 1 trauma center.

Patients: Surgical and trauma intensive care unit (ICU) patients mechanically ventilated for more than 48 hours and suspected by clinical parameters to have VAP since December 1, 1997.

Interventions: Upon entry into study, patients had protected specimen brush (PSB) and TA cultures taken and were then randomized to treatment based on results of PSB or TA cultures.

Results: Thirty patients were treated per PSB data, and 28 were treated by TA data. APACHE-II scores at entry into study were well matched. Antibiotic treatment days were significantly lower for the PSB-based therapy group compared with the TA-based therapy. Additional outcome measures included ICU and hospital length of stay. Rate of subsequent pneumonia and survival were significantly decreased in the PSB-based therapy group.

Conclusion: This study confirms the superiority with regards to efficacy and therapy for VAP based on a more accurate diagnostic approach compared with the previous standard of clinical diagnosis and TA data.

 

INTRODUCTION

Ventilator associated pneumonia (VAP) is defined as occurring 48 hours after intubation when new and persistent infiltrates and grossly purulent tracheobronchial secretions are present. This diagnosis may be further supported by fever (>38.3°), leukocytosis, and deterioration of gas exhange.^{1, 2} The clinical importance of VAP is well documented, occurring in approximately 20% of all ventilated patients,^2,3 24% to 44% in polytrauma patients, and frequently as high as 70% in patients with acute respiratory distress syndrome (ARDS).^2-9 The mortality of VAP, most of which can be attributed to the pneumonia itself, may be as high as 50%.^2,12

            The clinical diagnosis of VAP, especially in trauma patients, has been problematic. The diagnostic accuracy of portable chest roentgenograms in intensive care unit (ICU) patients for the diagnosis of pneumonia has been very low.^13-17 Colonization of the endotracheal tube has been recognized to occur very quickly and this reduces the diagnostic accuracy of tracheal aspirate to 50%.^18-20 Bronchoscopy by itself aids little in the diagnosis because the ports become contaminated by the upper airway flora upon insertion into the endotracheal tube.^21-23 The protected specimen brush (PSB) was introduced in 1979 to address this problem.⁹ When used with quantitative culture techniques, its efficacy has been repeatedly verified in numerous studies.^2,9,12 Over the past decade, bronchoscopic PSB and bronchoalveolar lavage (BAL) with quantitative cultures have become the gold standard with regard to diagnostic accuracy for VAP.

            We have previously shown that two nonbronchoscopic techniques, PSB and BAL, have a high degree of diagnostic concordance with bronchoscopic PSB in trauma patients with multiple injuries.² However, despite the diagnostic accuracy of these quantitative approaches, clinical improvement related to improved diagnostic accuracy has not been demonstrated. This study examines the clinical outcomes of therapy based on nonbronchoscopic PSB with quantitative cultures compared with tracheal aspirate with qualitative cultures in surgical ICU patients.

 

METHODS

This clinical study was approved by the institutional review board at our hospital. Patients were selected if they had been ventilated for more than 48 hours and were considered by the attending physician to have a VAP on clinical grounds (ie, fever, leukocytosis, change in the character of the sputum, and a new infiltrate seen on chest roentgenogram) with no previous pneumonia during this hospitalization. Under current standards at our institution's surgical ICU, these patients, if not enrolled in the study, would have undergone nonbronchoscopic PSB for quantitative analysis and tracheal aspirate analysis for the diagnosis of pneumonia. After obtaining informed consent, 58 ventilated adult patients in our surgical ICU were prospectively enrolled in the study.

            The procedures listed below were performed on all patients within 2 hours of enrollment in the study. All patients underwent nonbronchoscopic PSB first. Using a microbiology specimen brush (Microvasive cat no. 1650, Boston Scientific Corporation, Watertown, Mass, Figure 1), the catheter was inserted through the endotracheal tube to approximately 35 cm or until resistance was met (Figure 2). A specimen was obtained by expressing and retracting the inner catheter and brush in the standard fashion. The brush tip was then cut using a sterile wire cutter (Figure 3) and placed in one mL of nonbacteriostatic saline processed by our laboratory for quantitative culture within 2 hours. PSB culture was considered positive and reported only if 1000 CFU/ml were isolated in the specimen. A tracheal aspirate specimen was also obtained in standard fashion and processed by our laboratory for culture (nonquantitative) and sensitivities.

            Each patient was then randomly selected by closed-envelope draw to have therapy for VAP based on the PSB quantitative culture or tracheal aspirate culture. Therapy was initiated based on these data only (ie, earliest antibiotic initiation time was 24 hours after study entry). The clinical team caring for the patient was given only one culture result (either PSB or tracheal aspirate). They were intentionally blinded to the other result. Antibiotic selection was left to the discretion of the clinician. No empiric therapy was undertaken on study patients. Demographic data (age, gender, APACHE-II score at study entry, ventilator days at study entry) was obtained at study entry. Outcome data, which included PSB culture results, tracheal aspirate culture results, ICU length of stay, hospital length of stay, antibiotic days (number of antibiotics times the number of days on antibiotics), antibiotic patient charge, subsequent diagnosis of pneumonia during this hospitalization (including the culture result of the subsequent pneumonia), and survival to hospital discharge, were collected and tabulated on all patients. After the results were tabulated, a comparison of outcome data between patients treated based on PSB data versus tracheal aspirate data was performed using one-way analysis of variance (ANOVA). Statistical significance threshold was P. 05.

 

RESULTS

We enrolled 23 women and 35 men in our protocol (Table). The average age of the patients was 42.5 years. PSB was positive in 37/58 patients (66%). Tracheal aspirate culture was positive in all patients (100%). The number of organisms isolated per PSB culture was 0.77 versus 1.93 for the tracheal aspirate group, which had 28 patients. The averaged APACHE-II scores at study entry were 22.6 ± 2.6 versus 22.7 ± 2.8 for the PSB-treated group and the tracheal aspirate-treated groups, respectively (P = not significant). The antibiotic treatment days (ie, the number of antibiotics used each day times the number of days of therapy) were significantly lower for the PSB-treated group (4.4 ± 3.7 days) than for the tracheal aspirate-treated group (29.8 ± 9.5 days; P < .0001). Consequently, the antibiotic patient charge was significantly lower for the PSB-treated group ($557 ± $545 versus $4089 ± $1817; P < .0001). The numbers of ICU days were also reduced for the PSB group compared with the tracheal aspirate-treated group (11.5 ± 5.8 versus 23.0 ± 9.2 days; P < .0001). Subsequent pneumonia based on clinical and PSB data later during the course of this same hospitalization tended to be more frequent in the tracheal aspirate group (71% incidence versus 13% incidence; P < .0001). Figures 4 and 5 show the details of the patients' courses during the study. Overall survival was improved in the group of patients treated based on the more accurate PSB data (90% versus 68%; P = .038).

 

DISCUSSION

The diagnosis and therapy of VAP has been difficult both for the trauma surgeon and the intensivist. The lack of specificity of the clinical examination and the lack of specificity of tracheal aspirate has rendered them both of little value in diagnosing VAP.^5-8 The diagnostic accuracy of PSB, both by bronchoscopic and nonbronchoscopic approaches, has been validated.^18-23 However, the question of therapeutic efficacy has not been addressed until now. Our study is the first prospective randomized one to look at the efficacy of treating VAP by a more accurate nonbronchoscopic approach. Our study has shown patient outcome improvement not just from a resource utilization standpoint but survival as well. This study also addresses the lack of utility of tracheal aspirate cultures. The specificity of tracheal aspirate cultures was poor (in the range of 60% to 65%) compared with the PSB data, correlating well to the literature.^6,9,10,12 In the recent consensus statement of the American Thoracic Society, the diagnostic accuracy of tracheal aspirate (nonquantitative) with regard to diagnosing VAP was rated poor at best.²⁴ In reviewing Figures 4 and 5, which detail the patients' courses during the study, several very important findings can be noted:

1. Treatment with antibiotics when PSB culture is negative appears harmful.

Seven patients in the tracheal aspirate treated-group had negative PSB cultures

   and yet received antibiotic therapy. Of these patients, 5 developed a second pneumonia and 3 of the 7 patients died (43% mortality). However, in the PSB group, where the PSB was negative and thus the patients did not receive antibiotics, none of the 12 patients developed a second pneumonia or died.

2. Treatment with multiple antibiotics based on tracheal aspirate culture when PSB culture is positive (but has defined fewer bacteria as pathogens) promotes an increased incidence of subsequent bacterial pneumonia. The mortality rate of a second VAP seems relatively constant (between 25% and 30%), which correlates with published literature.^3-6 Patients with both positive PSB and tracheal aspirate cultures in the PSB group had fewer second pneumonias (4/18 patients [22% incidence] than patients in the tracheal aspirate group (15/21 patients [71% incidence]). A plausible explanation is that the tracheal aspirate-treated group was treated with multiple antibiotics whereas the PSB-treated group was treated with a single antibiotic, resulting in greater morbidity.

3. Although the numbers are small, treatment with multiple antibiotics in the tracheal aspirate group when the PSB culture was positive was associated with a higher mortality even when the patients did not develop a second pneumonia. Stated differently, if we look at mortality in patients that were treated when the PSB culture was positive, either with multiple antibiotics in the tracheal aspirate group or a single antibiotic in the PSB group, the mortality rate of patients that did not develop a second pneumonia was higher in the tracheal aspirate group (2/6 patients [33%] versus 2/14 patients [14%]; P < .001).

 

CONCLUSION

Based on these findings, the following recommendations can be made with regard to therapy of VAP in trauma/surgical ICU patients. First, in ventilated patients, PSB- or BAL-based cultures should be the diagnostic tests of choice. Bronchoscopy is not required to obtain these specimens. Subsequent antibiotic therapy should be based on these culture results. Therapy based on tracheal aspirate data is harmful when the PSB is positive or negative. As the PSB is much more specific and limits antibiotic use, the risk of developing of a second bacterial pneumonia is lessened and associated morbidity is decreased.

         This study does not address the utility of empiric antibiotic therapy as all patients received therapy after the culture results were obtained. This study also may have a bias factor built in. Duration of antibiotic therapy was defined by clinician evaluation. If the clinicians were treating for longer duration because of lack of comfort with the accuracy of tracheal aspirate cultures, perhaps this adversely affected the outcome of this study. It was a point of significant discussion prior to the initiation of the study. However, we felt that despite the potential introduction of this selection bias, the clinician caring for the patient was in the best position to assess therapeutic efficacy of an antibiotic regimen.

         The American Thoracic Society in its consensus statement on VAP²⁴ asked for a prospective randomized study to help clarify the question of "Does a more accurate approach to diagnosis necessarily yield improved outcome?" Our study begins to answer this question at least with regard to trauma patients. Studies evaluating the role of empiric therapy are underway and should further clarify issues regarding VAP.

 

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Table. Outcome Measures

Figure 4. Patient course for the PSB-treated group.

Figure 5. Patient course for the tracheal aspirate-treated group.