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Respiratory infections: what to expect from molecular tools?

The INHALE trial: designing a prescribing algorithm to aid antibiotic choices for the BIOFIRE® FILMARRAY® Pneumonia plus (PNplus) Panel

April 21 • P4394

D. Zaneeta1, V. I. Enne1, V. Gant2, D. M. Livermore3

1) University College London, London, United Kingdom
2) University College Hospital, London, United Kingdom
3) University of East Anglia, Norwich, United Kingdom

Background: The NIHR-funded INHALE Programme aims to improve antimicrobial stewardship through molecular diagnostics for HAP/VAP in ICUs.  Its first phase selected the BIOFIRE® FILMARRAY® Pneumonia plus Panel as the best-performing relevant test, and this is now deployed at point of care (POC) in 12 UK ICUs, with patients randomized to FilmArray-guided or Standard antimicrobials.  The test seeks 34 organism and gene targets, providing results in 1.5h. The results’ complexity, combined with rapid round-the-clock availability, prompted us to design an antimicrobial prescribing algorithm to support clinicians at the point of decision.  To our knowledge, this is the first instance of prescribing advice being directly linked to a rapid PCR test.

Materials/methods: We designed the algorithm based on (i) organism and resistance gene targets detected alone or in combination, (ii) national resistance surveillance data and (iii) patient’s allergy status. Narrow spectrum agents were preferred, and good antimicrobial stewardship encouraged. Site microbiologists, ICU pharmacists, and ICU clinicians were consulted and local adaptation allowed. 

Results: Where single organisms are found the algorithm favours, e.g. temocillin vs. Enterobacterales, flucloxacillin vs. MSSA and co-amoxiclav vs. Haemophilus influenzae; discontinuation is advised if no organism is found and the patient lacks convincing evidence of infection; broader spectrum agents are favoured for combinations of organisms. Among 10 adult sites, 4 adopted thealgorithm essentially unaltered and 2 with minor variation only. Common concerns were: unwillingness to adopt: (i) temocillin for Enterobacterales; (ii) ceftazidime vs. Pseudomonas; or (iii) cephalosporins for patients with mild ß-lactam allergy. There was considerable debate apropos infection control implications of ICU-based (rather than laboratory-based) detection of carbapenemase producers. Substantial variation was needed at 2 paediatric ICUs, principally because temocillin lacks a paediatric licence.

Conclusions: Prescribing algorithms such as this will ensure that potential benefits of rapid syndromic tests are realised at POC. Whilst it was not possible to impose a single algorithm at all hospitals, core elements and principles were retained. An early audit of RCT results indicates that most test-arm treatments are being guided by the algorithm, as sought. The sites’ willingness to adopt this approach illustrates the potential for a major shift to molecular-guided chemotherapy.

filmarray

Pneumonia Panel

Paper poster