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A second look at azithromycin
SAN DIEGO—Though azithromycin is commonly administered as a short-course antibiotic for infections such as strep throat and sinusitis—it is sold commercially as Zithromax Z-Pak and is the most often prescribed antibiotic in the U.S.—it has been disregarded as a candidate for treating multidrug- resistant bacterial infections, as previous testing in standard laboratory media demonstrated that azithromycin does not kill those bacteria. But a recent study by researchers at the University of California, San Diego (UCSD) School of Medicine has found that when tested under conditions that more closely resemble the human body, azithromycin kills many multidrug-resistant bacteria very effectively.
The bacteria focused on in the study, known as gram-negative rods due to their cell wall structure and their shape, included Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. All three are extremely antibiotic-resistant, and are leading culprits of hospital-acquired infections in patients recovering from trauma or surgery.
Senior author Dr. Victor Nizet, professor of pediatrics and pharmacy at the UCSD School of Medicine, and colleagues discovered that growing the gram-negative rod bacteria in mammalian tissue culture media as opposed to bacteriologic media dramatically affected the bacteria's sensitivity to azithromycin. Furthermore, the drug-resistant bacteria were totally eliminated when the team combined azithromycin with the antibiotic colistin or with antimicrobial peptides that are naturally produced by the body during infection.
The team then moved on to a mouse model of multidrug-resistant A. baumannii pneumonia, treating the mice with a single dose of azithromycin at a concentration similar to that given intravenously to human patients. One day after infection, the treated mice had 99 percent fewer bacteria in their lungs than untreated mice, effectiveness that was also seen in mouse models of multidrug-resistant P. aeruginosa and K. pneumoniae infections, in which a single dose of azithromycin led to a more than 10-fold reduction in bacterial counts.
“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 Nizet, senior author of the study, which appeared in EBioMedicine. “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.”
Both the U.S. Centers for Disease Control (CDC) and the World Health Organization cite P. aeruginosa, K. pneumoniae and A. baumannii as growing threats in terms of the spread of antibiotic resistance. The CDC ranks P. aeruginosa as a Serious Threat. This classification is for significant antibiotic-resistant threats that “are not considered urgent, but these threats will worsen and may become urgent without ongoing public health monitoring and prevention activities.”
According to the CDC, approximately 2 million people are infected with antibiotic-resistant bacteria in the United States each year, with at least 23,000 deaths as a result of such infections.