Infection control
comparable to what you’d find in a real-world setting. The biofilms were also extremely thick, consistent with previous studies that have examined the tubes extubated from patients. Up to 84% of these tubes are completely covered in biofilm, increasing the likelihood of VAP. On a more encouraging note, the researchers found that combining antibiotics with ‘matrix degrading enzymes’ represented a promising treatment strategy. These enzymes, which break down the biofilm’s
VAP recurrences are common, and bacterial biofilms often persist on the ventilator tubes.
they were able to learn more about the behaviour of the underlying pathogens. They were also able to run experiments, discovering which treatment strategies might work best.
“Companies could use this model to help find new drugs and new tube coatings to prevent VAP,” comments Harrison. “I like the idea of making something that allows us to study microbiology in a new way but might also produce something useful.”
Stubborn infections
Unlike typical lab models, which are not particularly accurate, the researchers’ new model provides a good simulation of what happens within the ventilated patient’s airways. They used the same type of tubes that are deployed in real-world settings, along with a ‘synthetic ventilated airway mucus’. This is a strategy that has been deployed for cystic fibrosis previously, but never for VAP. “We were aware of studies where people had taken real endotracheal tubes, and put them in a microbiological growth medium,” says Harrison. “But that was a standard lab medium that doesn’t actually mimic the chemistry inside an infected host. We were able to review the literature, come up with a current best guess of how we could make synthetic ventilated airway mucus, and then combine that with sections of tube to see how bacteria and fungi grew on them.” VAP, she notes, is fundamentally a biofilm infection. Invading bacteria – which may come from the patient’s own body or from the healthcare environment – form tight-knit communities on the surface of the tube, encased in a slimy matrix. The researchers wanted to see if they could grow biofilms on the tubes, akin to the ones that occur in patients. They found that they could. What’s more, the biofilms in question were strikingly hard to eradicate. In contrast to typical lab models, in which antimicrobial treatments are quite effective, these bacterial and fungal species were stubbornly averse to treatment. High concentrations of antimicrobials were required to have any effect –
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protective slime layer, made the bacteria more vulnerable to attack and allowed the researchers to halve the concentration of antibiotics needed. “The problem with VAP is that if you start to break down a biofilm, it’s got nowhere to go except the lungs,” points out Harrison. “We’d have to be very, very careful that we weren’t just moving the bacteria. So how useful it would be, I don’t know. But it is a proof of principle that if you can combine something that breaks down that biofilm matrix with an antimicrobial, you can improve treatment.”
Searching for answers
Harrison sees her work more as a starting point for fellow researchers, who might be interested in finding new drug targets and working out what kind of drugs are most appropriate. Ultimately, she would like to develop two versions of the model – an open-access version for those conducting fundamental research, and another for commercial purposes. Recently, her team received a grant from the National Biofilms Innovation Centre to work with a local robotics and 3D printing specialist. Together, they are looking to design a 3D printed bivalve ventilator, with a view to improving their model of the patient’s body. The attraction of these kinds of models, she says, is not just that they’re more naturalistic; they could also help eradicate animal research. “The animal model of VAP is really horrible – if you’re having to ventilate a mouse or a pig, it’s a really invasive procedure,” says Harrison. “It’s one of those areas where, if we can replace animal use, it’ll have a massive ethical impact, as well as potentially being more informative.” Although VAP is a stubborn problem, which continues to fox healthcare systems across the world, Harrison is confident that there will be ways to improve on the standard of care. “My personal gut feeling is you’re going to have to have a combination of a new kind of tube with an antimicrobial treatment,” she says. “I don’t think we’re going to find a magic tube that prevents any host tissue or bacteria from sticking to it, but we might be able to find something that’s a bit better than what we’ve got.”
Practical Patient Care /
www.practical-patient-care.com
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Shutterstock.com
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