INHALE: the impact of using FilmArray Pneumonia Panel molecular diagnostics for hospital-acquired and ventilator-associated pneumonia on antimicrobial stewardship and patient outcomes in UK Critical Care—study protocol for a multicentre randomised controlled trial

Abstract

Background Hospital-acquired and ventilator-associated pneumonias (HAP and VAP) are common in critical care and can be life-threatening. Rapid microbiological diagnostics, linked to an algorithm to translate their results into antibiotic choices, could simultaneously improve patient outcomes and antimicrobial stewardship. Methods The INHALE Randomised Controlled Trial is a multi-centre, parallel study exploring the potential of the BioFire FilmArray molecular diagnostic to guide antibiotic treatment of HAP/VAP in intensive care units (ICU); it identifies pathogens and key antibiotic resistance in around 90 min. The comparator is standard care whereby the patient receives empirical antibiotics until microbiological culture results become available, typically after 48–72 h. Adult and paediatric ICU patients are eligible if they are about to receive antibiotics for a suspected lower respiratory infection (including HAP/VAP) for the first time or a change in antibiotic because of a deteriorating clinical condition. Breathing spontaneously or intubated, they must have been hospitalised for 48 h or more. Patients are randomised 1:1 to receive either antibiotics guided by the FilmArray molecular diagnostic and its trial-based prescribing algorithm or standard care, meaning empirical antibiotics based on local policy, adapted subsequently based upon local microbiology culture results. Co-primary outcomes are (i) non-inferiority in clinical cure of pneumonia at 14 days post-randomisation and (ii) superiority in antimicrobial stewardship at 24 h post-randomisation (defined as % of patients on active and proportionate antibiotics). Secondary outcomes include further stewardship reviews; length of ICU stay; co-morbidity indicators, including septic shock, change in sequential organ failure assessment scores, and secondary pneumonias; ventilator-free days; adverse events over 21 days; all-cause mortality; and total antibiotic usage. Both cost-effectiveness of the molecular diagnostic-guided therapy and behavioural aspects determining antibiotic prescribing are being explored. A sample size of 552 will be required to detect clinically significant results with 90% power and 5% significance for the co-primary outcomes. Discussion This trial will test whether the potential merits of rapid molecular diagnostics for pathogen and resistance detection in HAP/VAP are realised in patient outcomes and/or improved antibiotic stewardship. Trial registration ISRCTN Registry ISRCTN16483855. Retrospectively registered on 15 July 2019

Multicentre evaluation of two multiplex PCR platforms for the rapid microbiological investigation of nosocomial pneumonia in UK ICUs: the INHALE WP1 study

“…This is now underway (Trial ID: ISRCTN16483855). 17 Note that this study and RCT are distinct from a recently published trial for nebulised amikacin with the same name 18…”

Infection Point of Care Tests (POCT) in simulated vignettes can improve the education of Antibiotic Stewardship Programmes. An observational comparative study of Clinicians vs Medical Students

“…These factors limit the generalisability of the results. Present ndings would bene t from replication in more complex vignettes that provide the option to de/escalate and in real-time clinical settings, both of which are currently underway 47,48 .…”

Combination of a multiplex pneumonia panel and Gram staining for antimicrobial selection to treat lower respiratory tract infection

“…Early identification of the causative organism by the pneumonia panel and detection of drug-resistance genes within hours may facilitate early administration of effective antimicrobial agents, thus improving the outcomes of pneumonia treatment. The benefits of pneumonia panels have already been reported [ 1 – 7 ] and a randomized controlled trial comparing pneumonia panels with standard diagnostic protocols is currently underway [ 8 ]. Sputum quality, which is one of the most important factors influencing the results of pneumonia panels, can be evaluated using Gram staining.…”