Common Antibiotic Wrongfully Ignored as Option to Fight Superbugs

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Evidence proves that a commonly prescribed drug is able to wipe out multiple potentially deadly antibiotic-resistant infections.

Evidence proves that a commonly prescribed drug is able to wipe out multiple potentially deadly antibiotic-resistant infections.

Azithromycin, commercially called Zithromax Z-Pak, is often prescribed to combat bacterial infections that can be treated in short courses — such as strep throat and sinusitis. Although this medication is the most commonly prescribed drug for those types of ailments, it is not given to patients with the more serious multidrug-resistant bacterial infections. Senior author Victor Nizet, MD, and colleagues from the University of California, San Diego School of Medicine (UCSD) and Skaggs School of Pharmacy and Pharmaceutical Sciences have demonstrated that this long-overlooked drug can be a powerful treatment option.

“Unquestioning adherence to a single standardized lab practice may be keeping doctors from considering potentially life-saving antibiotics — therapies that are proven safe and readily available in any hospital or pharmacy,” Nizet, professor of pediatrics and pharmacy at UCSD, said in a news release.

How is it that this commonly prescribed antibiotic has been overlooked as an option for more stubborn infections?

Previous testing showed that azithromycin did not kill any of the bacteria so it was never used to treat antibiotic-resistant illnesses. In this latest report, the researchers tested the medication on extremely antibiotic-resistant strains of 3 different Gram-negative rods — Pseudomonas aeruginosa, Klebsiellapneumoniae, and Acinetobacterbaumannii. These strains often infect people who have a compromised immune system or experienced a trauma or surgery.

“While bacterial agars and testing media are useful in providing consistency for hospital laboratories around the world,” Nizet explained. “The actual infection is taking place in the blood and tissues of the patient, and we know the action and potency of drugs can change quite dramatically in different surroundings.”

According to the study published in EBioMedicine, the key component was growing the bacteria in mammalian tissue culture media as opposed to standard bacteriologic media. The mammalian tissue is the same material that is used to sustain human cells in the lab, so the sensitivity to azithromycin is different.

“This pharmaceutical activity is associated with enhanced [azithromycin] cell penetration in eukaryotic tissue culture media and striking multi-log-fold synergies with host cathelicidin antimicrobial peptide LL-37 or the last line antibiotic colistin,” the authors wrote.

Furthermore, the process was moved to a mouse model in order to verify the results in a live infection system. The mice were infected with multidrug-resistant A. baumannii pneumonia, given a single dose of azithromycin, and just 24 hours later had a 99% reduction in bacteria in the lungs when compared to the control mice. Comparable results — a reduction in bacteria by more than 10-fold – were seen in mouse models with P. aeruginosa and K. pneumoniae.

The experiment ultimately revealed that when used in combination with colistin or the body’s naturally produced antimicrobial peptides, azithromycin can eliminate the antibiotic resistant superbugs.

“If something this simple could be overlooked for so many years, what else might we be missing?” Nizet concluded.

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Elizabeth Cerceo, MD | Credit: ACP
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