A laboratory approach to testing antibiotic efficacy that uses tissue culture instead of less natural lab media suggests that a medical dogma, that azithromycin should not be used against highly antibiotic-resistant superbugs, could be overturned.
“Unquestioning adherence to a single standardized lab practice may be keeping doctors from considering potentially lifesaving antibiotics – therapies that are proven safe and readily available in any hospital or pharmacy,” says senior author Dr. Victor Nizet.
Years of testing azithromycin in standard laboratory media with nutrient broth has concluded that the drug does not kill the most nefarious multidrug-resistant bacterial infections, say the researchers publishing a study in EBioMedicine.
This research has found, however, that in conditions more closely mimicking bodily infections, the drug could actually have a role.
Dr. Nizet, a professor of pediatrics and pharmacy at the University of California-San Diego School of Medicine, says:
“While bacterial agars and testing media are useful in providing consistency for hospital laboratories around the world, 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.”
Dr. Nizet says, talking about a “complacency” in the approaches to drug evaluation in the decades since the discovery of penicillin, there needs to be a more holistic focus on the wider immune system interactions with antibiotic effects, adding:
“If something this simple could be overlooked for so many years, what else might we be missing?”
The researchers collaborated with the Skaggs School of Pharmacy and Pharmaceutical Sciences. They outline azithromycin (sold under the brand names Zithromax and Zmax) as the most commonly prescribed antibiotic in the US.
The superbugs of most concern to the authors – because of an “ever-worsening antibiotic resistance crisis” and a lack of drug candidates in the development pipeline – are Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii.
These opportunistic infections strike debilitated patients in hospitals rather than healthy hosts. At sometimes deadly risk from these pathogens are patients with weakened immune systems, or those coming through trauma or surgery.
In the study, simply growing these gram-negative rod bacteria in mammalian tissue culture media instead of standard laboratory media made a big difference in their azithromycin sensitivity.
“Even more striking,” say the researchers, the drug-resistant superbugs were “completely wiped out” when azithromycin was paired with the antibiotic colistin or with antimicrobial peptides produced naturally by the human body during infection.
The research team took these promising results and tested azithromycin in a live infection environment – in a mouse model of multidrug-resistance in pneumonia caused by A. baumannii.
Dr. Nizet and team found that 24 hours after a human IV dose-equivalent injection of azithromycin, the treated mice had 99% fewer bacteria in their lungs than untreated mice.
Similarly, in mouse models of multidrug-resistant P. aeruginosa and K. pneumoniae infections, a single dose of azithromycin reduced bacterial counts by more than 10-fold.
The potential importance of such findings is illustrated by the authors’ introduction, which cites that, in the US alone, half of hospital-acquired (nosocomial) infections are by drug-resistant bacteria, leading to about 99,000 deaths every year. What is more, drug-resistant bacteria increase health care costs by $5 to $10 billion annually.