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Antibiotic First Discovered Decades Ago May Stop Resistant Superbugs

Superbugs resistant to colistin – a last-resort antibiotic – may have a new foe in octapeptins, antibiotics discovered decades ago that recently have been found to be effective against multidrug-resistant gram-negative bacteria.

With bacterial pathogens growing increasingly resistant to available drugs and few new antibiotics in the pipeline, a new study on an antibiotic not used since its discovery more than 4 decades ago offers hope in the fight against superbugs.

Since antibiotics first came into use more than 70 years ago, many of the bacteria these drugs are designed to target have developed antibiotic resistance, leading to an increasing number of hard-to-treat infections. The Centers for Disease Control and Prevention (CDC) notes that there are 2 million antibiotic-resistant infections resulting in 23,000 deaths in the United States each year due to these superbugs. Today, about 1 out of every 3 antibiotic prescriptions given to patients are inappropriately prescribed for viral or other infections, and a study published in 2016 by the CDC and Pew Charitable Trusts found that doctors are too often prescribing the wrong antibiotic. That study concluded that only 52% of the 44 million antibiotic prescriptions given for sinus infections, middle ear infections, and pharyngitis were for the first-line drugs recommended based on established guidelines.

In 2017, the World Health Organization (WHO) released a report suggesting that there is a serious lack of new antibiotics in development, underscoring that antibiotic resistance is a global health emergency set to undermine decades of progress in modern medicine. The problem of colistin resistance has contributed to more multidrug-resistant (MDR) and even extensively drug-resistant (XDR) bacteria no longer treatable with what is considered a last-resort antibiotic. Now, a new study published in the journal Cell Chemical Biology is adding evidence to suggest that octapeptins, not used since their discovery decades ago, are effective against XDR pathogens no longer susceptible to colistin.

The rediscovered antibiotics are a class of lipopeptides structurally related to colistin, the authors, researchers from the University of Queensland, University of Melbourne, and Monash University in Australia write.

“Octapeptins were discovered in the late 1970s but were not selected for development at the time, as there was an abundance of new antibiotics with thousands of people working in antibiotic research and development,” said study author Matthew A. Cooper in a recent press release. “Given the very few researchers left in this field now, and the sparse pipeline for new antibiotics, we’ve used modern drug discovery procedures to re-evaluate its effectiveness against superbugs.”

The research team synthesized octapeptin to produce an antibiotic called octapeptin C4, finding that it was more active in vitro than colistin against MDR strains of gram-negative bacteria. Such bacteria increasingly exhibit resistance to multiple antibiotics and are of concern in health care settings where they cause pneumonia, bloodstream infections, wound or surgical site infections, and meningitis.

“Gram-negative bacteria are harder to kill as disease organisms because they have an extra membrane to penetrate that is often hidden by a capsule or slime layer which acts to camouflage them from drugs and our immune system,” Dr. Cooper is quoted to have said in the press release. “Octapeptin showed superior antimicrobial activity to colistin against extensively resistant gram-negative bacteria in early pre-clinical testing. In addition, octapeptin was shown to be potentially less toxic to the kidneys than colistin.”

With these findings, the research team posits that octapeptins may be key to the development of a new generation of antibiotics to fight superbugs.