The Centers for Disease Control and Prevention said these numbers are only a conservative estimate. Among other reasons, they come only from infections reported in hospitals and do not address ones that occur in nursing homes and other health care facilities.
The numbers underline the importance of not overusing antibiotics.
In as many as half of the cases studied, antibiotic use was not necessary or was even inappropriate, such as in viral infections, for instance, the researchers said.
The report also warns against the danger of running short on effective treatments against infection while the number of new antibiotics being developed fails to meet short-term needs.
"If we're not careful, we will soon be in a post antibiotic era," CDC director Tom Frieden said.
"And, in fact, for some patients and some microbes, we are already there. Losing effective treatment will not only undermine our ability to fight routine infections, but also have serious complications, serious implications, for people who have other medical problems," he said.
Most of the 18 microbes included in the study are common, and were divided into three categories depending on their degree of risk: urgent, concerning and important.
Within the urgent group, there are three of particular interest: they are called carbapenem-resistant enterobacteriaceae, C. difficile, and drug-resistant gonorrhea, he said.
The first of those is a "nightmare bacteria" that can essentially resist all antibiotics and kill people who get it in their blood.
C. difficile is a life-threatening infection associated with 14,000 deaths and a quarter of a million hospitalizations per year.
As for gonorrhea, there are more than 800,000 infections in the United States each year, with a growing proportion resistant to all available medication.
The way to fight all this is to prevent infection and the spread of resistance, through immunization, safe food preparation and hand washing, the CDC said.