A Trojan Horse Antibiotic Could Help Fight Antibiotic Resistant Bacteria

Researchers have developed a new “Trojan horse” antibiotic that could slip past the defense systems of drugs that have resistances to common antibiotics. These new Trojan horse antibiotics have been used in early clinical trials and proved promising, working as effectively as the best current treatments.

The drug is cefiderocol, and trials of the antibiotic were done on 448 patients with either urinary tract infections or kidney infections. According to the study recently published in the journal Lancet Infectious Diseases, the trials of the drug found that they were at least as effective as current treatments.

Smuggling In Antibiotics With Iron Covers

The Trojan horse metaphor comes from the fact that the antibiotics, like the Trojan horse of legend, disguise themselves in a package that let the drugs slip past the defense systems of the bacteria. The antibiotics camouflage themselves in iron molecules that the bacteria need to survive, when the iron molecules are absorbed by the bacteria the antibiotics are ingested as well.

Bacteria have two outer membranes that defend them from harmful chemicals, so antibiotics must find ways to damage this membrane or bypass it. The porin channels that make up the membrane are capable of changing/adapting to prevent entry of antibiotics, and bacteria also have a system of pumps that can expel drugs out of the cell.

A researcher from the drug Company Shinogi Inc., Dr. Simon Portsmouth, explained to Telegraph that one of the immune responses of the human body is to create an environment within the body that is iron-poor. This means that the bacteria respond by increasing their own iron intake to compensate. Cefiderocol functions by latching onto the iron molecules and getting transported through the defensive outer layer of the bacteria along with the iron. Once the drug has managed to penetrate the defenses of the bacteria, it kills it much like regular antibiotics do. Portsmouth explained to Telegraph:

“Cefiderocol was found to be both safe and tolerable in a population of older patients who were very ill with complex comorbid conditions and a wide range of multidrug-resistant pathogens. Our results support cefiderocol as a novel approach that might be used to overcome Gram-negative resistance”.

An Effective New Treatment For Hard To Treat Diseases?

The findings of the trials show that cefiderocol is a possible counter to gram-negative bacteria, including carbapenem-resistant strains of bacteria. Carbapenem is one of the most effective antibiotics out there, and its use is usually reserved for only cases of bacteria that are high-risk and resistant to other forms of antibiotics. This means that carbapenem-resistant bacteria are some of the most dangerous and most difficult to treat infections and that there are currently no effective alternative antibiotics that don’t have serious side effects/consequences.

Illustration of how drug-resistant bacteria multiply. Photo: By NIAID – NIH – , Public Domain, https://commons.wikimedia.org/w/index.php?curid=41858152

According to ScienceDaily, the study examined 448 adults who had either a UTI or a bacterial kidney infection, giving them three daily infusions of either cefiderocol or another antibiotic called imipenem-cilastatin. Cefiderocol was reportedly at least as effective as imipenem-cilastatin, cefiderocol had an efficacy rate of around 73% while imipenem-cilastatin had an efficacy rate of around 55%.

However, while early clinical trials are encouraging, larger and more comprehensive trials of the drug will be needed to ensure that it is effective and ready for use in the medical field as a whole. Portsmouth explained that there are currently trials of the drug being done on cases of pneumonia, including ventilator-associated pneumonia and pneumonia acquired in hospitals. Also occurring are studies in patients with carbapenem-resistant infections.

An Urgent Need For New Treatments

Antibiotic-resistant bacteria is one of the biggest concerns in the medical research field, and the cefiderocol study comes just as a report released by Public Health England (PHE) stated that the number of bloodstream infections caused by antibiotic-resistant bacteria increased by around 35% in the four years between 2013 to 2017. As reported by the Telegraph, if the current rate of antibiotic resistance stays level, it is suspected that by the year 2050 around 10 million people could die a year due to antibiotic resistance.

As reported by The Guardian, England’s chief medical officer, Dame Sally Davies, said that we could be facing a “return to the dark ages” of surgery, with surgery becoming life-threatening once more if antibiotics resistance continues to go unchecked. Davie’s remarks coincide with the report by Public Health England which finds that 3 million different surgical procedures, from hip replacements to cesarean sections, could potentially become life-threatening due to hospital-acquired infections being impossible to treat with current antibiotics.

Photo: Brett_Hondow via Pixabay, CC0

The PHE report urged moderation in the use of antibiotics, stressing that antibiotics should not be overused as they currently are. It is estimated that one in every three patients are provided with antibiotics when they are recovering or before they are even operated on. Overuse of antibiotics also include cases where antibiotics are prescribed for minor problems like sore throats and coughs, which are frequently caused by viral infections and therefore not even affected by antibiotics. According to the PHE, around four-tenths of people still expect that they will receive an antibiotic during walk-in visits for symptoms relating to throat, ear, sinus or chest colds.

While researchers are hard at work at developing new treatments for antibiotic resistant diseases, the PHE is launching a new campaign that stresses people should accept the advice of their doctor regarding when antibiotics are needed, and that doctors be more discerning with prescribing antibiotics. Paul Cosford, PHE’s medical director, explained to The Guardian that there is an urgent need that society preserves the power of antibiotics for when they are really needed, and that although taking antibiotics just in case may seem harmless it can actually have devastating consequences for the future of people’s health.

Recent efforts to reduce the overuse of antibiotics can boast a little success, with the rate of antibiotic use falling by around 6.1% in the years between 2014 to 2017 within England. Meanwhile, data on antibiotic usage in the US suggests there is a slight decrease in outpatient prescribing since 2014. Despite this, usage rates in the US remain high by international standards.

It is also important that people take their antibiotics exactly as prescribed by their doctor, and not cease use of the antibiotic before their doctor tells them to. As Davies says, the issue of antibiotic resistance is “not just an issue for doctors and nurses; the public have a huge role to play.”