To print this page, select "Print" from the File menu of your browser salon.com > Health & Body June 11, 1999 URL: http://www.salon.com/health/feature/1999/06/11/antibiotics Scary as hell People are dying because antibiotics can't keep up with resistant bugs. - - - - - - - - - - - - By Arthur Allen Bacterial resistance threatens to disable our health-care system, but it still brings a glint of wonderment to J. Glenn Morris' eyes. "From a scientific standpoint, it is fascinating to watch," says Dr. Morris, chief epidemiologist at the University of Maryland Medical Center. "As a physician, it's scary as hell." Across the United States, and the world, bacteria and other microorganisms are challenging medical arsenals. A half century of antibiotic overuse -- in doctors' offices and hospitals, but also in livestock feed and antibacterial hand creams -- has provoked the opposite of its intent. Instead of a world safe from infectious bugs, we have a world where the most stubborn bugs survive. Already, drug-resistant bacteria are killing thousands of people each year. It's not too simplistic to say that we're racing the bugs to save such endeavors as neonatology, organ transplants and cancer chemotherapy, none of which could exist without effective antibiotics. "You don't know how the race is going to go," says Christopher Walsh, a Harvard Medical School professor of pharmacology and biochemistry. "You could be a strategic optimist and say the basic science is bound to save us in the nick of time. Or you could be a defensive pessimist and say we're going to be in a post-antibiotic era for a while." At the 750-bed downtown Baltimore hospital monitored by Morris, a bearded man with gentle blue eyes, the post-antibiotic era has, in a limited sense, already arrived. In 1992 the medical center had the dubious honor of becoming one of the first hospitals in America to detect colonies of vancomycin-resistant bacteria called enterococci. Vancomycin -- a drug known in intensive care units as "the Big Gun," or "The Mighty Vanc"-- is a powerful antibiotic. Doctors began flooding surgical patients with vancomycin in the 1980s when Staphylococcus aureus, the cause of "staph" infections, developed widespread resistance to an earlier miracle drug, methicillin. Today, methicillin-resistant staphylococcus and vancomycin-resistant enterococcus are endemic to Morris' hospital. Carriers are isolated in separate rooms where staff and visitors are ordered to wear gloves and gowns. But despite efforts to control their spread from patient to patient, the bugs "are here to stay," says Morris. Random samples show vancomycin-resistant enterococci in up to 25 percent of all patients at the hospital, Morris says. What this means is that vancomycin resistance isn't just in the hospital -- it's walking the red-brick streets of the city spread below Morris' ninth-floor window. And it kills, although Morris can't say how often. (At most hospitals, infection control officers won't even talk to reporters.) "No hospital will admit that people are dying of resistant bacteria they acquired in that hospital," says Morris. But they are dying. In 1997, 90,000 people died in U.S. hospitals while infected with hospital-acquired bacteria -- 70 percent of which were antibiotic-resistant strains, according to Dr. Stuart Levy of Tufts University in Massachusetts (although infection was not necessarily the major cause of all or even a majority of those deaths). Luckily for most of us, enterococci are dangerous only to patients with compromised immune systems. But enterococci will seem like mother's milk if and when vancomycin resistance becomes a factor in staph infections. Staphylococcus aureus "can cause havoc and death to even otherwise healthy people," says Levy. Staphylococcus, a bacteria that colonizes the noses of one in five people, has proven over the years to be among the most adaptable bacteria. Targeted with penicillin in 1942, by 1948 staph was largely resistant. Erythromycin was introduced in 1952 and quickly lost its bite, leading to raging hospital infections. Methicillin, introduced in 1960, was effective for longer -- until the mid-1980s. Now vancomycin is the magic bullet. It's not that bugs are "outsmarting" us; they're as dumb as they seem. As a class, though, they are certainly less individualistic than we are. Bacteria are indifferent to how they get their genes. They'll mutate, have sex with cousins and strange species or gobble up free-floating DNA. Sworn to the Hippocratic oath, doctors will throw everything in their arsenal at bacteria to save one patient. "A million bacteria get their heads blown off for every one that survives" an antibiotic, says Dr. Abigail Salyers of the University of Illinois. But a few do survive -- and each resistant survivor and its progenitors gain Lebensraum in the body each time the antibiotic is used again, killing off the bacteria that lack genes to adapt. In December 1996, epidemiologists at the Centers for Disease Control and Prevention got a long-anticipated but still chilling report. A child in Japan had contracted a staph aureus infection that appeared to thumb its nose at vancomycin. CDC officials have since confirmed four U.S. cases of near-resistant Staphylococcus -- in Michigan, New Jersey and New York, and last month in an undisclosed Midwestern hospital. The appearance of the bug in scattered hospitals suggests that, like a series of supercomputers seeking answers to a complicated equation, staphylococci around the world are on the verge of cracking the vancomycin code. "It's evolution in parallel," says Morris. "There are all sorts of fairly nasty scenarios that you could dream up." The mutant bugs could be controlled if surveillance was vigorous enough. But many managed-care companies now limit expensive lab cultures, and there is no national reporting requirement for staph infections. The CDC is relying on a fairly new network of monitoring sites to detect and study the organisms. To control vancomycin resistance, the worst thing hospitals can do is to throw more vancomycin at staph. But they often have no alternative. Morris and his colleagues spend a certain amount of time balancing their commitment to patients and the tragedy of the commons -- the idea that pursuing individual benefit can ruin collective resources. And although vancomycin use is being reined in, what's best for the individual is always the last word. "The clinician says, 'I've got a patient who is dying and I think I can keep them alive and, well, to hell with the guy in the corner who's saying don't use vancomycin,'" says Morris. "You can get into some pretty heavy philosophy -- to put it mildly." Perhaps the spookiest aspect of this looming threat is that, as in a Gabriel García Márquez story, it has been foretold. "Public officials have become complacent about the staph problem. Young doctors have never witnessed babies dying of staph pneumonia," wrote a Kentucky pediatrician named Warren Wheeler upon his retirement in 1972. "It would amaze me if in the future some new strains don't develop which will smoulder without recognition for a while, passing from one human to another, juicing up their virulence as they do until they add the property of methicillin resistance and explode." Within a decade, as Wheeler anticipated, methicillin-resistant staph was widespread. Vancomycin, isolated from organisms that a missionary gathered on a jungle path in Borneo, stepped into the breech. Should vancomycin fail there is no new magic bullet to replace it -- for now, at least. The FDA is poised to approve a new drug, Synercid, that can kill staphylococcus and a range of other bacteria. It is said to have serious side affects, though, and even more troubling news emerged at a conference of microbiologists in Chicago last week. There, it was revealed that 1 percent of human enterococci are already resistant to Synercid. How did this happen? A similar antibiotic has been fed to livestock since 1974, creating resistant enterococci in chickens. Scientists hypothesize that the chicken bacteria passed their resistance genes to human enterococci after their hosts became food. "Bacteria from livestock and hospitals communicate," says the German microbiologist Wolfgang Witte. "They communicate via meat." Several drug companies are working on new antibiotics; Pharmacia & Upjohn says that Zyvox, from a new class of antibiotics called oxazolidinones, should be on hospital pharmacy shelves next year. Many bacteria have been genetically decoded, giving scientists plentiful targets for new drugs -- although identifying gene targets is only the first step in a process that takes a decade or more. In addition, "resistance to new drugs is a cyclical process," says Harvard's Walsh. "Every time we introduce a drug and use it widely we guarantee resistance. It's only a question of how long. There is no one-time solution, but continual cycles of discovery." Most promising, in the long run, are vaccines, which prepare our immune systems to deactivate bugs without the help of antibiotics. Vaccines have worked wonders in the recent past. In the 1970s and early 1980s, drug-resistant Haemophilus influenza type B bacteria killed or disabled thousands of children every year. The so-called Hib vaccine was introduced in 1985; in 1997 there were fewer than 300 serious Hib-related cases. The most promising new vaccine target is Streptococcus pneumoniae, which leads to nearly 40,000 deaths, 500,000 cases of pneumonia and 7 million ear infections every year. Over-prescription of antibiotics has created nasty new strains of pneumococcus, but it's hoped that a childhood pneumococcus vaccine, which has performed well in large trials, could work as well as the Hib shots have. An experimental vaccine against Staphylococcus aureus showed promise in mice, according to research published in Science last month. But vaccines take even longer than drugs to develop, and "the reason we don't have a staphylococcus vaccine has nothing to do with people not having tried," says Paul H. Axelsen, a professor of pharmacy at the University of Pennsylvania. In any case, antimicrobial resistance is a moving target -- no one knows which bugs will be the biggest threats in 15 years, when the current crop of new drugs and vaccines hits the market. Pessimism is the default setting in the field. "I doubt we'll get a crisis or a plague," says Salyers. "More like the gradual erosion of our ability to control human diseases." Adds Morris, "We're starting to see the closing of the window, of the antibiotic era. The question is how fast it closes." salon.com | June 11, 1999