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Essential Science: Breakthrough for patients with pneumonia

By Tim Sandle     May 6, 2019 in Science
New research, published in The Lancet Infectious Diseases, presents the first clinical results with CAL02 in patients suffering from severe pneumonia, the first cause of infectious mortality in the world.
The findings are of significance for pharmaceutical companies and the medical sector. This is in the context of a time of great struggle for antibiotic companies given the increase in instances of antibiotic resistant bacteria. What is of particular global concern is the acceleration of resistance. U.S. Centers for Disease Control and Prevention (CDC) data finds that many high-income countries are entering a “post antibiotic era.”
READ MORE: Genetic test for antimicrobial resistance
Based on the study findings, CAL02 might well bring a total revolution in the treatment of severe infections. CAL02 is a universal, simple, and highly efficient non-antibiotic drug capable of neutralizing the bacterial toxins known to cause severe, and sometimes deadly, complications. CAL02 aims at becoming the first drug patients with a severe infection receive and will transform medical care.
The breakthrough comes from Combioxin SA, which is a Swiss-based clinical-stage biotechnology company founded in 2015.
The crystal structure of adenylosuccinate lyase (ASL) from Thermatoga maritima.
The crystal structure of adenylosuccinate lyase (ASL) from Thermatoga maritima.
UCLA-DOE Institute for Genomics and Proteomics via Microbe Wiki
CAL02 offers a new solution for medical professionals, in the form of a medication intended to be simple, affordable and highly efficient. The reason why there is considerable interest in CAL02 is because it does not induce resistance, overcoming the issues limiting antibiotics in terms of bacteria undergoing gene transfer in order to confer resistance to a given antimicrobial compound. A further advantage with CAL02 is that it can be administered by a medical professional before pathogen identification.
CAL02 is composed of liposomes engineered to entrap and neutralize a large panel of bacterial toxins, particularly those medically identified as causing severe complications. A liposome is a spherical vesicle having at least one lipid bilayer. In medical research, liposomes are considered one of the most versatile and promising drug-carrier devices.
The conceptual difference with CAL02 is that unlike antimicrobials which seek to kill viable bacteria, ‘antivirulence approaches’ like CAL02 have been tailored not to kill but instead to disarm bacteria by targeting their virulence factors.
The application of CAL02 is focused on neutralizing bacteria’s most deadly weapons - the toxins which promote colonization and bacterial growth, disrupt tissue barriers, and facilitate invasiveness. According to the Antimicrobial Resistance Industry Alliance, such toxins can also impede the host’s immune defense against the pathogen, and create favorable conditions for the growth and dissemination of opportunistic bacteria.
Microbes: Staphylococcus is a common bacteria which can cause anything from a simple boil to horribl...
Microbes: Staphylococcus is a common bacteria which can cause anything from a simple boil to horrible flesh-eating infections
Vano Shlamov, AFP/File
Based on clinical trial results, which were designed to assess the safety and efficacy of CAL02, carried out at an intensive-care-unit with patients with severe community-acquired pneumococcal pneumonia, the results obtained are encouraging.
Pneumococcal pneumonia is a form of bacterial pneumonia triggered by the bacterium Streptococcus pneumoniae (or ‘pneumococcus’). This is a common type of community-acquired pneumonia. Initial symptoms include severe chill, later including a severe fever, cough, shortness of breath, rapid breathing, and chest pains.
This new study was a human trial conducted as a randomized, double-blind, placebo-controlled trial, using a patient population where 58 percent of those involved were in septic shock and 42 percent were under invasive mechanical ventilation at the time of treatment.
The test subjects received two intravenous administrations of CAL02 or, alternatively, they were administered a placebo. The patients were then tracked over the course of 29 days. The results showed that CAL02 was as safe as the placebo. The data further showed that those who were treated with CAL02 showed a faster clinical improvement. This included a faster resolution of organ dysfunctions. There was also a reduction in the time that those on mechanical ventilation needed to continue using this equipment.
Going forward this alternative approach to combating infections could provide a significant improvement in terms of the survival rates in terms of the infections which pose the greatest threat, like hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia, sepsis, endocarditis, or osteomyelitis.
The Lancet has published an editorial comment along with the research paper. The research paper is entitled “One step closer to precision medicine for infectious diseases”, ranking “this study a medical breakthrough”.
Essential Science
This undated photo released on April 20  2016 by XL Catlin Seaview Survey shows a diver checking the...
This undated photo released on April 20, 2016 by XL Catlin Seaview Survey shows a diver checking the bleached coral at Heron Island on the Great Barrier Reef
This article is part of Digital Journal's regular Essential Science columns. Each week Tim Sandle explores a topical and important scientific issue. Last week we considered how the health of corals is important for ensuring the biodiversity of the oceans. The health of corals provides a key performance indicator of the health of the planet, especially in relation to climate change. A new digital mosaic map illustrates this importance.
The week before, we looked at how, in some circumstances, an imbalance of bacteria in the mouth has an association with the development of neurodegenerative diseases, such as Alzheimer's.
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