Azithromycin proves strikingly effective against drug-resistant superbugs

Multi-drug resistant Gram-negative rod bacteria Acinetobacter baumannii is being killed by the common antibiotic azithromycin (green) in the presence of a human antimicrobial peptide naturally present at infection sites. CREDIT: UC San Diego School of Medicine

Researchers have found that the common antibiotic azithromycin kills many multidrug-resistant bacteria very effectively.

Multi-drug resistant Gram-negative rod bacteria Acinetobacter baumannii is being killed by the common antibiotic azithromycin (green) in the presence of a human antimicrobial peptide naturally present at infection sites. CREDIT: UC San Diego School of Medicine

Their findings could prompt an immediate review of the current standard of care for patients with ‘superbug’ infections.

Short courses of azithromycin are often prescribed to cure common bacterial infections. But azithromycin is never given to patients with some of the most nefarious multidrug-resistant bacterial infections. That’s because years of testing in standard laboratory media — the nutrient broth that helps bacteria grow — concluded that azithromycin doesn’t kill these types of bacteria.

“Unquestioning adherence to a single standardised 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,” said Victor Nizet, MD, professor of paediatrics and pharmacy, University of California, San Diego School of Medicine. “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.”

The bacteria at the centre of this study are Gram-negative rods. Nizet’s team studied extremely antibiotic-resistant strains of three medically important Gram-negative rods: Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. These opportunistic pathogens rarely infect healthy people but instead strike debilitated patients in hospitals, such as those with weakened immune systems, or following trauma or surgery, sometimes with deadly consequences. The Centers for Disease Control and World Health Organization have warned that resistance is rapidly spreading in these species, and no new antibiotic candidates are on the horizon.

Superbugs were completely wiped out when azithromycin was paired with colistin

In this study, Nizet’s team found that simply growing these Gram-negative rod bacteria in mammalian tissue culture media instead of standard bacteriologic media made a huge difference in their sensitivity to azithromycin. Even more striking, 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.

To test these promising laboratory results in a live infection system, Nizet and team moved the experiment into a mouse model of multidrug-resistant A. baumannii pneumonia. They treated the mice with a single injected dose of azithromycin at a concentration that mimics the amount typically given by IV to human patients. Twenty-four hours after infection, azithromycin-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 study suggests that the general effectiveness of antibiotics in the decades since the discovery of penicillin has led to complacency in our approach to antibiotic evaluation. In the current era of ever-increasing antibiotic resistance, they recommend a more holistic approach that considers both the bug and the patient’s immune system.

The study findings are published in the journal EBioMedicine.