Antibiotic resistance is sweeping the globe, with so-called “superbugs” sickening 2 million people and killing 20,000 in the U.S. alone each year. The problem is widespread enough that that World Health Organization is coordinating an international effort similar to a microbiological war on the proliferating germs.

But a key weapon might have been under everyone’s nose for years, according to a new study, which may prove to be controversial.

Three common drug-resistant superbugs were completely wiped out when fought with azithromycin, the common antibiotic which is often marketed as “Z-Pak,” according to the researchers from the University of California, San Diego School of Medicine, who published their study in EBioMedicine today.

The implications could be staggering – considering what could be gained, and what may have been lost, owing to the non-use of the common drug.

“If something this simple could be overlooked for so many year, what else might we be missing?” said Victor Nizet, M.D.,a professor of pediatrics and pharmacy at the school who is the lead author.

“(This is) probably just the tip of the iceberg,” Nizet told Drug Discovery and Development. “We anticipate many additional hidden activities will be revealed when antibiotic therapy is contextualized to physiologic conditions and in synergy with the innate immune system.”

Three bacterial strains known as Gram-negative rods are opportunistic infections which generally only strike immune-compromised patients in hospitals, or following traumatic wounds or surgery, according to the scientists. The three strains have been singled out as a danger by the Centers for Disease Control and Prevention, especially since there are no new antibiotic candidates currently in the pipeline to combat them.

Zirthromax, the “Z-Pak” common to doctors’ offices worldwide, has not been used to fight the superbugs. Traditional lab tests in standard bacteriologic media had shown the standard antibiotic to have no effect.

But the new study shows that growing the potentially-deadly bacteria in mammalian tissue culture media made a huge difference – and proves that in real hospital settings, the Zithromax could turn the tide against the spreading germs.

“Even more striking, the drug-resistant superbugs were completely wiped out when azithromycin was paired with the antibiotic colistin or with antimicrobial peptides produced natural by the human body during infection,” said the authors.

“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. “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 standard bacteria-testing media should not be attacked or ridiculed, he added. But testing for actual therapeutic value should also be considered, he said. For instance, the azithromycin tests were conceived when a hospice patient with an infected cardiac device couldn’t be injected with preferred antibiotics. Instead, that patient showed improvements with the basic oral antibiotic, Nizet said.

Superbugs have been considered a major international health concern. Independently of the WHO announcement last month, the White House announced its own initiative to combat the rise of the new strains of infectious germs earlier this year. Some drug makers have been developing some antibiotics to combat superbugs such as MRSA.