Antibiotic Exposure Does not Affect Clearance of Alveolar Pathogens

Author(s):
Richard Betzold; Bradley Dennis; Wonder Drake; Judith Jenkins; Daryl Patton; Christopher Fonnesbeck; Addison May

Background:

Ventilator-associated pneumonia (VAP) is a common but poorly understood condition in the trauma population.  We have previously shown that mechanically ventilated trauma patients can develop high pulmonary bacterial burden without developing clinical symptoms of VAP. Factors associated with pathogen clearance versus subsequent development of VAP are unknown. 

Hypothesis:

We hypothesized that antibiotic exposure is associated with increased pathogen clearance in surveillance mBAL.

Methods:

Critically injured adults ventilated for > 2 days were enrolled. Patients underwent daily surveillance mini-bronchoscopic alveolar lavage (mBAL) while ventilated for 14 days or until extubation. Standard semi-quantitative cultures were performed and results were blinded from clinical use. Standard patient management was performed by the clinical team. Patients suspected of VAP underwent bronchoscopic-BAL (bBAL) and semi-quantitative culture, with VAP defined as clinical symptoms plus > 10⁴ CFU bacteria. All mBAL with >10⁴ CFU were assessed for antibiotic exposure with a spectrum covering the isolated bacteria and bacterial burden was assessed in the following 24 hours.

Results:

60 patients enrolled were ventilated a median of 9 days.

37 patients had clinical suspicion for VAP and had a bBAL. 26 had confirmatory growth on bBAL. On surveillance mBAL, 20 had bacterial burden < 10⁴ CFU. 13 had mBAL > 10⁴ CFU without suspicion of VAP, all of whom had culture clearance. 56 patients had antibiotic exposure, and 31 were treated for VAP. 4 patients had no exposure, and none developed VAP.

There were 75 positive surveillance mBAL specimens. 46 mBAL samples had 10⁴ CFU growth and were not exposed to any antibiotic on the sample day. Of these, 12/46 had either stable or increased growth in 24 hours. Thus, 74% (34/46) had either clearance or a decrease in CFU without any antibiotic exposure. 29 mBAL samples had 10⁴ CFU growth and were exposed to antibiotic therapy on the sample day. 19 had antibiotic exposure that covered the pathogen. Of these, 3/19 had either stable or increased growth in 24 hours. Thus, 84% (16/19) had either clearance or decreased pathogen growth. 10 had antibiotic exposure that did not have activity against the specific bacterial growth. 1/10 had increased bacterial growth and the remaining 9/10 had either clearance or a decrease in CFU. The three groups were not statistically different on chi-squared analysis.

Conclusions:

Contrary to our hypothesis, clearance of pathogenic bacteria on surveillance mBAL was not affected by antibiotic exposure, whether or not the antibiotic had activity against the pathogen.