Biomarker-guided exclusion of ventilator-associated pneumonia (VAP) was not associated with a reduction in antibiotic use, according to study results published in Lancet Respiratory Medicine.

Antibiotic use remains high among patients with suspected VAP, contributing to antibiotic resistance increasingly observed in these patients. Researchers sought to determine whether measurement of bronchoalveolar lavage could effectively and safely improve antibiotic stewardship in patients with suspected VAP.

Therefore, the researchers conducted VAPrapid2 (Biomarker-Based Exclusion of VAP for Improved Antibiotic Stewardship; Identifier: NCT01972425), a randomized controlled trial that screened 360 patients from 24 intensive care units from 17 National Health Services hospital trusts in England, Scotland, and Northern Ireland. To qualify for enrollment, patients must have been intubated and received mechanical ventilation for ≥48 hours and had suspected VAP, as evidenced by several different criteria. Confirmed VAP was defined as growth of a potentially pathogenic organism of ≥104 colony forming units per mL of bronchoalveolar lavage fluid.

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Patients were randomly assigned to either biomarker-guided recommendation on antibiotics (n=104) or a control group consisting of routine antibiotics (n=106). All clinicians were masked to intervention assignments until biomarker test results were made available. The distribution of antibiotic-free days in the 7 days after bronchoalveolar lavage was the primary outcome.

In the intention-to-treat analysis, no difference was observed between the 2 groups in terms of the primary outcome (P =.58). There was also no difference in the primary outcome of the distribution of antibiotic-free days in the 7 days after bronchoalveolar lavage in the per-protocol analysis (P =.28). A small, transient increase in oxygen requirements was associated with bronchoalveolar lavage.

At Day 7, the median number of antibiotic days in both groups was 6 (hazard ratio [HR], 0.84; 95% CI, 0.63-1.12). There were no between-group differences at 14 or 28 days in terms of antibiotic-free days. Factors associated with impaired trial processes included established prescribing practices, reluctance for bronchoalveolar lavage testing, and dependence on a “chain” of trial-related protocols and procedures.

Limitations of the study included the high number of assay failures in the early phase of the trial as well as the lack of a dedicated investigator responsible for suggesting antibiotic discontinuation.

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The researchers wrote that “lack of adoption of the technology and clinician behavior had a greater influence on trial outcomes than did test performance” and “future trials of diagnostic tests for [VAP] should incorporate detailed implementation strategies informed by prior characterization of factors that influence prescribing and diagnostic decision making” in VAP.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Hellyer TP, McAuley DF, Walsh TS, et al. Biomarker-guided antibiotic stewardship in suspected ventilator-associated pneumonia (VAPrapid2): a randomised controlled trial and process evaluation [published online December 3, 2019]. Lancet Respir Med. doi:10.1016/S2213-2600(19)30367-4