Contrary to current medical dogma, researchers report that the common antibiotic azithromycin kills many multidrug-resistant bacteria very effectively - when tested under conditions that closely resemble the human body and its natural antimicrobial factors. The researchers believe the finding, published in the journal EBioMedicine, could prompt an immediate review of the current standard of care for patients with certain so-called "superbug" infections.
Azithromycin is the most often prescribed antibiotic in the United States, where short courses can cure common bacterial infections such as strep throat and sinusitis. But azithromycin, also sold commercially as Zithromax Z-Pak, 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.
"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 researchers said.
The bacteria at the center of this study are Gram-negative rods, so-called due to their cell wall structure (they appear "negative" in a classic typing test known as the Gram stain) and their shape. The researchers 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.
The researchers found that simply growing these Gram-negative rod bacteria in mammalian tissue culture media - the same stuff used to sustain human cells in the lab - 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, the 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 percent 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.
According to the authors, 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.
"If something this simple could be overlooked for so many years, what else might we be missing?" the researchers said.
Based on material originally posted by University of California - San Diego.