Pneumonia is one of the main symptoms of severe COVID-19 disease and, because many critically ill COVID-19 patients can no longer breathe by themselves they are put onto mechanical ventilators. These pump air through a tube into the lungs, helping the patient to survive. However, unfortunately the ventilation also increases the risk of bacteria entering the lungs, establishing a further infection known as ‘secondary pneumonia’.

INHALE study Investigator, Dr Vicky Enne, Senior Research Fellow in the Division of Infection & Immunity, said: “Bacterial pneumonias need urgent antibiotic treatment and left untreated can cause death: administering the right antibiotics as quickly as possible at diagnosis is therefore critical to survival.

“Unfortunately it takes 2 to 3 days to grow the bacteria in the laboratory, so it’s conventional to start with broad-spectrum antibiotics, active against many types of bacteria, then to refine treatment once the lab results come through.

“To significantly reduce this delay our study aims to accurately identify the bacteria in under an hour, thereby allowing doctors to pinpoint the best antibiotic in quick time.”

The INHALE trial, conducted by UCL, University of East Anglia and Norwich Clinical Trials Unit, is evaluating cutting-edge ‘molecular diagnostics’ to identify bacteria directly from pneumonia patients’ sputum (fluid produced in lungs), without the need for lab culture. The test, developed by biotech company bioMerieux BioFire, can pinpoint 26 pneumonia pathogens and can detect whether these have critical antibiotic resistances.

A test result is obtained in around one hour and the information aims to give the clinician early guidance on which antibiotics to use – meaning ones likely to be active against the bacteria detected. It also discourages the use of unnecessary antibiotics, which can contribute to the development of further antibiotic resistance.

INHALE has been evaluating this approach in ‘run of the mill’ ventilator pneumonia patients at 12 ICUs in England for the past six months. Now, in the present pandemic, INHALE is being temporarily refocused to investigate the secondary bacterial pneumonias that COVID-19 patients get, and to guide their treatment. It has already been used in over 50 patients at hospitals including University College London Hospitals (UCLH), the Royal Free, Watford General, Chelsea and Westminster and Liverpool University Hospitals. 

Dr Enne added: “Antibiotic resistance is as much of a threat during the pandemic as it was before COVID-19. The BioFire test allows doctors to give the right antibiotics to those that need them and prevents their unnecessary use, thus ensuring we are doing everything we can to spare these valuable drugs.”

Dr David Brealey, ICU Consultant at UCLH and Senior Lecturer at UCL Medicine, said: “Having the BioFire to help identify pneumonia has been invaluable in managing COVID-19 patients on the ICU at UCLH. These patients are so sick, we cannot wait days to get a result back from the lab, and this machine gives the result direct to the treating clinician within the hour. Real, actionable intelligence is making a difference to the way we treat our patients.”

Study Chief Investigator, Dr Vanya Gant, Consultant Microbiologist at UCLH and Honorary Senior Lecturer in the Division of Infection & Immunity, said: “The INHALE team are very proud to have been able to so rapidly adapt the paused INHALE clinical trial to deliver vital clinical results to frontline ICU clinicians in an hour by repurposing our testing equipment and infrastructures - with UCLH’s doctors in particular taking the lead in a record time to implementation. And what's more - we've put in analyses that will tell us what this might mean in terms of patient benefit.”

The study’s Co-Chief Investigator, Professor David Livermore from the University of East Anglia, said: "COVID came suddenly and changed everything. It disrupted INHALE's original plan. But it has also created a vital medical need: to test if real time information on secondary bacterial pneumonias improves treatment of the sickest, ventilated Covid-19 patients. And we've quickly refocused INHALE to do exactly that."

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  • Clouded areas in X-ray of lungs depict pneumonia infection. Credit: Dr Vicky Enne

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