Long ignored as a treatment option for certain serious bacterial infections, azithromycin proves strikingly effective in new lab and animal tests
Contrary to current medical dogma, researchers at University of California, San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences 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 June 10 by 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.
"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," said senior author Victor Nizet, MD, professor of pediatrics and pharmacy. "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 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. 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.
In this study, Nizet's team 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, 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 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?" Nizet said.
Co-authors of this study (DOI 10.1016/j.ebiom.2015.05.021) also include Leo Lin, Poochit Nonejuie, Jason Munguia, Andrew Hollands, Joshua Olson, Quang Dam, Monika Kumaraswamy, Heriberto Rivera, Ross Corriden, Mary E. Hensler, Michael D. Burkart, Joe Pogliano, and George Sakoulas, UC San Diego; and Manfred Rohde, Helmhotz Centre for Infection Research, Germany.
This research was funded, in part, by the National Institutes of Health (grants HD071600, AI057153 AI052453, AR052728 and GM073898).
Heather Buschman | EurekAlert!
Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences
What does congenital Zika syndrome look like?
24.03.2017 | University of California - San Diego
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy