Researchers’ hopes are raised after a trial using monoclonal antibodies to prevent pneumonia in ventilated intensive care patients gets good results
Researchers recently showed that an injection of monoclonal antibodies can be used to decrease the virulence of Staphylococcus aureus bacteria in patients who are hooked up to breathing machines in hospital. The phase II trial was carried out by the IMI project COMBACTE-NET, as part of the SAATELLITE study, using a monoclonal antibody developed by AstraZeneca called Suvratoxumab.
Patients in intensive care units (ICUs) who are breathing with the help of ventilating machines are at high risk of contracting pneumonia. The “superbug” Staphylococcus aureus bacteria make their way into healthy lungs by attaching to the medical tubing that connects to the outside world. S. aureus is extremely virulent and increasingly resistant to antibiotics.
Not killing, just taming
The objective of the trial was to see if patients whose lungs are already colonised by S. aureus could avoid pneumonia by being dosed with a one-off shot that would block the bacteria’s virulence, i.e. the potential for infection.
The results were promising. The researchers enrolled about 200 ventilated ICU patients in a double blind placebo controlled trial. The percentage of people in the placebo arm that contracted pneumonia was 26%, while those who had received the monoclonal antibodies injection was 18%. This is a relative reduction of 31%. Dr Bruno François from the University Hospital of Limoges, who was involved in the SAATELLITE study, calls this “huge”.
"...maybe in ten or 20 years from now we will use antibiotics much less and monoclonal antibodies much more.”
“This was the first trial with this type of drug to be used as a preventative,” says Dr François. He is cautiously optimistic about the results. “This could represent a true opportunity to decrease the number of pneumonia infections in the ICU without needing any antibiotics. Of course it’s only a phase two so you would need a confirmatory trial, but it’s completely innovative.”
“There are many examples of very promising drugs in phase two and that fail in phase three so you always have to be careful, but maybe in ten or 20 years from now we will use antibiotics much less and monoclonal antibodies much more.”
Dr François emphasises the difference between monoclonal antibodies and vaccines: “It’s not really vaccination, because your own body is not creating antibodies against the pathogen. We used antibodies that are already available. It’s more like we’re pre-empting infection – but we’re not trying to kill them, we are blocking their virulence factor.” This means that this drug isn’t affected by bacteria’s evolving protection. “There is no mechanism of resistance with this type of drug – it doesn’t exist.”
Video: IMI has invested heavily in antimicrobial resistance (AMR) research
Not completely new, but completely innovative
Monoclonal antibodies (mAbs) are proteins that your body produces to neutralise bacteria or viruses. Suvratoxumab works by targeting a very specific toxin generated by S. aureus. Ever since antibodies were discovered in the 19th century, scientists have dreamed of harnessing this specificity to fight off all types of infectious diseases and cancer. Ironically, the idea was overtaken with the advent of antibiotics, whose ability to kill infections made them the favoured mode of treatment for decades, until selection pressure made them increasingly resistant.
IMI’s COMBACTE projects feature a number of consortia trying out other new and innovative ways to combat antimicrobial resistance. Dr François’ team is involved in a sister consortium, called COMBACTE-MAGNET, which is currently running a similar trial using monoclonal antibodies against Pseudomonas aeruginosa. Another COMBACTE consortium is trying to new ways to prevent Clostridium difficile, while others work on innovative antibiotics.
Dr Bruno François is Management Board member of COMBACTE-NET, and work package lead of COMBACTE-NET’s SAATELLITE study. He is Specialist in Intensive Care Medicine and Anesthesiology and Head of the Clinical Investigation Center at University Hospital of Limoges.