Antibiotic Gentamicin Can Be Effective Without Causing Deafness, Study Finds

Antibiotic Gentamicin Can Be Effective Without Causing Deafness, Study Finds
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Scientists discovered the subtypes of gentamicin — a broad-spectrum antibiotic often used to treat bacterial infections in people with cystic fibrosis (CF) — that are more likely to cause deafness, and created a new formulation that is as effective at eliminating bacteria but much safer for patients.

“We’ve developed a simple method of reformulating the drug that should be put to use as soon as possible,” Anthony Ricci, PhD, professor of otolaryngology at the Stanford School of Medicine, and the study’s senior author, said in a press release.

Ricci and his colleagues are planning to write to the U.S. Food and Drug Administration (FDA), recommending the agency to change its requirements on the way gentamicin is manufactured, as current instructions “are making people go deaf,” Ricci said.

The findings were reported in the study, “Dissociating antibacterial from ototoxic effects of gentamicin C-subtypes,” published in the journal PNAS.

Gentamicin is a popular and inexpensive broad-spectrum antibiotic that belongs to a class of compounds called aminoglycosides, which have been in use since the 1950s and favored for their high potency and low storage costs. The antibiotic is used in hospitals to treat a wide variety of bacterial infections in susceptible patients, including newborns and those with chronic diseases like CF.

Despite its popularity and widespread use, statistics indicate that up to 20% of gentamicin-treated patients will have some degree of irreversible hearing loss. According to Alan Cheng, MD, a professor of otolaryngology (diseases of the ears and throat) at Stanford and the study’s co-senior author, this is especially problematic for young children, “as they rely on hearing to acquire speech.”

“What this study shows is that the formulation that is currently in a hospital bottle of gentamicin is not optimized,” Ricci said, referring to the fact that sisomicin, the most toxic gentamicin subtype, is currently required by federal and international law to be part of its composition.

“If we just use the subtype that’s less toxic or change the formulation of this bottle, we can make the drug much less ototoxic,” Ricci said.

Since all gentamicin subtypes are approved for use by the FDA, it is likely that less toxic formulations would not have to be retested, allowing them to be quickly brought into clinical practice.

“Both individual and reformulated mixtures of C-subtypes demonstrated decreased ototoxicity while maintaining antimicrobial activity, thereby serving as a proof-of-concept of drug reformulation to minimizing ototoxicity of gentamicin in patients,” the researchers wrote.

The team also noted that the ototoxic properties of each gentamicin subtype seemed to be associated with the way each of them interacted with specific channels within the inner ear. More specifically, they discovered that the antibiotic subtypes that bound most strongly to these channels tended to be the least toxic.

Researchers are now planning to create a new aminoglycoside that could further lower the risk of deafness.

“This discovery lays the groundwork for the discovery of safer antibiotic alternatives and future drug development,” Ricci said.

Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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