Dilution Factor of Quantitative Bacterial Cultures Obtained by Bronchoalveolar Lavage in Patients with Ventilator-Associated Bacterial Pneumonia

Abstract

Ventilator-associated bacterial pneumonia (VABP) is a difficult therapeutic problem. Considerable controversy exists regarding the optimal chemotherapy for this entity. The recent guidelines of the Infectious Diseases Society of America and the American Thoracic Society recommend a 7-day therapeutic course for VABP based on the balance of no negative impact on all-cause mortality, less resistance emergence, and fewer antibiotic treatment days, counterbalanced with a higher relapse rate for patients whose pathogen is a nonfermenter. The bacterial burden causing an infection has a substantial impact on treatment outcome and resistance selection. We describe the baseline bronchoalveolar lavage (BAL) fluid burden of organisms in suspected VABP patients screened for inclusion in a clinical trial. We measured the urea concentrations in plasma and BAL fluid to provide an index of the dilution of the bacterial and drug concentrations in the lung epithelial lining fluid introduced by the BAL procedure. We were then able to calculate the true bacterial burden as the diluted colony count times the dilution factor. The median dilution factor was 28.7, with the interquartile range (IQR) being 11.9 to 53.2. Median dilution factor-corrected colony counts were 6.18 log10(CFU/ml) [IQR, 5.43 to 6.46 log10(CFU/ml)]. In a subset of patients, repeat BAL on day 5 showed a good stability of the dilution factor. We previously showed that large bacterial burdens reduce or stop bacterial killing by granulocytes. (This study has been registered at ClinicalTrials.gov under registration no. NCT01570192.).

Keywords: bacterial burden; bronchoalveolar lavage; ventilator-associated bacterial pneumonia.

Copyright © 2017 American Society for Microbiology.

Figures

FIG 1

Regression between day 1 (D1) and day 5 (D5) dilution factors caused by BAL (n = 20). The lower and upper 95% confidence interval about the regression line and the 95% prediction interval (which refers to the observations) are indicated. The regression line was log(day 5 dilution factor) = 0.851 × log(day 1 dilution factor) + 0.299 (r2 = 0.714; P = 0.000003).

FIG 2

Demonstration of bacterial clearance attributable to granulocytes after adequate chemotherapy results in the decline of the bacterial burden to a point that returns the antimicrobial capability of the granulocytes. Blue lines, the bacterial burdens at hours 26 and 50. The difference between the lines is due to bacterial cell kill by granulocytes alone. Error bars represent standard deviations. Modified from the Journal of Infectious Diseases (4) with permission of the publisher.