Physician William Osler is famously quoted as saying: “Humanity has but three great enemies: fever, famine and war; of these by far the greatest, by far the most terrible, is fever.”

Osler, who was among the founders of Johns Hopkins Hospital, apparently was an incorrigible wit and prankster. But in this case, he wasn’t kidding.

In the mid- and late 19th century, when Osler was practicing, infectious diseases were the main human killers everywhere.

Even as late as 1900, the leading causes of death in the United States were influenza and pneumonia, tuberculosis and gastrointestinal infections, according to the U.S. Centers for Disease Control and Prevention.

Osler’s strong, emphatic words must have been inspired by the helplessness he and other physicians felt seeing otherwise healthy people felled by microscopic foes, against which few weapons existed.

Many aspects of social progress, including vaccines and improved hygiene, helped to change the causes of our deaths, but among the greatest was the widespread use of antibiotics, beginning with penicillin in the mid-1940s.

End of an age?

By 1950, Americans were dying mostly of heart disease and cancer, according to the CDC. Other worries already had replaced the tiny microbes that had caused so much death in the past.

Recently, however, some of the world’s most respected health care organizations have been using strong, emphatic words of warning about a growing threat from new versions of those old human enemies.

In September, while releasing a report on drug-resistant pathogens, CDC Director Dr. Tom Frieden told reporters: “If we’re not careful, we will soon be in a post-antibiotic era. And, in fact, for some patients and some microbes, we are already there.”  

On Jan. 8, Professor Jeremy Farrar, director of the Wellcome Trust, one the largest funders of medical research in the United Kingdom, told the BBC there was reason to worry that the “golden age” of antibiotics was coming to an end.  

“We’ve been through a wonderful era that goes back to the 1940s with the development of antibiotics,” Farrar said. “And we are coming to the end of that era, if we are not careful.”

The warnings are driven by increasing presence of microorganisms such as bacteria and fungi that cause human illnesses and have developed resistance to drugs, typically antibiotics, used to kill them. Health officials around the world also are warning about drug-resistant viruses such as HIV and influenza, and parasites such as those that cause malaria, but the CDC report didn’t detail those fears.

Much at stake

At least 2 million people a year get seriously ill from antibiotic resistant bacteria; at least 23,000 people die as a direct result of those infections, according to the CDC report released in September. The increasing prevalence of drug-resistant bacteria also is costing U.S. health-care system anywhere from $20 billion to more than $35 billion a year, according to the study.

Most troubling, perhaps, is the prospect of losing one of the most important tools in medical history.

Infections are still the leading cause of death in the word, responsible for about one-third of all deaths, but mainly because of disease in developing countries. In this country, infection has not made death’s top-five list in decades, but there’s some evidence of a new trend.

Between 1980 and 1992, mortality from infections increased by 58 percent and age-adjusted death rates increased by 39 percent, according to the CDC. Taken as a group, infectious diseases have become the third leading cause of death, according to the CDC.

“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,” Frieden said.  

“For example, things like joint replacements and organ transplants, cancer chemotherapy and diabetes treatment, treatment of rheumatoid arthritis. All of these are dependent on our ability to fight infections that may be exacerbated by the treatments of these conditions. And if we lose our antibiotics, we’ll lose the ability to do that effectively.”

Too much good

Among the culprits driving the rise of drug-resistant pathogens is the overuse of antibiotics, often in response to demand from uninformed patients, for treatment of illnesses against which they have no good effect, such as viral infections responsible for the flu and the common cold.

The situation is similar to other situations humanity faces in the postmodern world. Antibiotics, like pesticides and herbicides, for example, worked well and their use provided clear benefits, at least in the short term. And so they were used without too much thought about long-term effects. And like the debates about the costs and benefits of using chemicals in agriculture, there’s some argument that the dire warnings about drug resistance are overblown.

But Dr. A. Clinton White Jr., a physician and professor who heads the Division of Infectious Diseases at the University of Texas Medical Branch, doesn’t think they are.

“The reality of the situation is really quite disturbing,” White said. “I think that for a long period of time the benefits of antibiotics were so obvious that we ignored the down side.”

Simple evolution

Anywhere from a third to half of outpatients treated with antibiotics have illnesses that antibiotics won’t help, and the numbers are only a little better in hospitals, White said.

And while overuse of antibiotics is exacerbating the problem, any use of antibiotics promotes the rise of drug-resistant microbes, both White and the CDC report warn.    

“Some resistance is almost inevitable,” White said. “So we really have to stop and think that every time we use a dose of antibiotic, that’s one less dose we’ll have in the future.”

In the past, as one type of antibiotic lost its effect, doctors would begin using a new type. That’s becoming less of an option, however, because pharmaceutical companies are less interested in developing new antibiotic drugs.    

Farrar told the BBC that 20 years ago 18 companies around the world were producing new antibiotics; in 2013, there were four.

Almost 20 new antibiotics were developed and approved between 1980 and 1984, but less than 10 were between 2000 and 2012, according to the CDC report.

“It’s a real problem, and we have not quite figured out how to solve it,” White said. “Part of the solution is not using them when we don’t need to, and not using them for too long when we do need to.”

Some good news

The good news is that both physicians and the public have gotten wiser about antibiotic use, said Dr. Oscar Brown, an associate professor of pediatrics at the medical branch and director of Bay Colony Pediatric Center.

“We have made great strides over the past 15 years in reducing the amount of antibiotics we use,” Brown said.

For example, Brown said he sees fewer mothers these days who demand antibiotics for sick children when there’s a good chance they are suffering from a viral infection that antibiotics won’t help.

“We’ve effected a pretty good culture change and numbers indicate a fairly good drop in antibiotic use from about the late ’90s,” he said. “I’m not saying we have cured the problem, but we have done a better job of educating the public and doctors as well.”

Contact Associate Editor Michael A. Smith at 409-683-5206 or michael.smith@galvnews.com.

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