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Photomontage by Flint Born

Imagine a world without antibiotics, a world stripped of treatment for simple bacterial infections like strep throat, pneumonia, meningitis, or even ear infections. People born in the early 1930s may remember that such a world existed before sulfa drugs, the first widely used antibiotics, were discovered in mold. Because of those drugs and their successors, infections like meningitis and streptococcus that once sent millions to their graves now send hundreds of millions to the pharmacist for a few days' worth of medication.

There's a tendency to feel a bit smug about our conquest of bacteria. Well, it's true that bacteria have lost this battle, but they have not conceded the war. Mainly because of their ability to acquire new DNA from outside sources, divergent strains of bacteria appear continuously. Some varieties resist many widely used antibiotics, and others resist practically all microbicides, even new and expensive ones.

"It may be just a little to start off with," says associate professor of medicine Thomas O'Brien, M.D. '54, medical director of the microbiology laboratory at Brigham and Women's Hospital. "One bacterium will have a feature that gets in the antibiotic's way, slows it down just a little. The cell does something to protect itself, and it gradually begins to flourish. And then the game begins."

The "game" is natural selection, the process by which creatures find and exploit their niches in their environment. Antibiotic resistance is like a stronger beak that allows a finch to crack open a harder seed. Bacteria grow faster in the presence of drugs to which they're resistant because all the nonresistant bacteria they had fought with over food and resources suddenly die.

Whether we're working, eating, sleeping, or breathing, more bacteria live on each of us than people on planet Earth. We support civilizations of bacteria; each time we shake hands or jostle a fellow straphanger, cultures collide. Bacteria "mobilize," as O'Brien puts it, hopping from host to host, often without causing illness or even encountering antibiotic treatment. But as soon as the right antibiotic comes into play, all competition falls away, and the antibiotic-resistant bacteria bloom. Lately, such blooms have become increasingly troublesome for infectious-disease specialists.

"When you look at the percentages of bacteria that are resistant, you can see that they're progressive," says Robert Moellering, M.D. '62, Shields Warren-Mallinckrodt professor of medical research. "In 1940, all pneumococci were susceptible to penicillin treatment. In the United States today, 25 to 30 percent of all strains of pneumococci are resistant to penicillin. You can go class by bacterial class, antibiotic by antibiotic, and see similar trends of increasing resistance."

In addition to causing pneumonia, pneumococci also cause the majority of this country's cases of meningitis, making this potentially fatal disease increasingly difficult to treat as well. One of the few antibiotics that still kills drug-resistant pneumococci is vancomycin; however, the drug cannot effectively penetrate tissues in the spinal-cord lining, making it difficult to treat the most severe meningitis cases. Even when high doses of vancomycin are used, Moellering says, the treatment situation is still "borderline."

In addition, there's already been a disturbing emergence of vancomycin resistance in some bacteria. Because the drug attacks a fundamental point in the bacteria's cell-wall construction, experts had predicted that resistance to this antimicrobial might never materialize. As it happened, however, some types of bacteria have acquired a set of genes that eliminate and replace the portion of cell wall to which vancomycin normally binds.

Plasmids--packages of genes--frequently pass back and forth between different kinds of bacteria. Some plasmids are like resistance toolkits; each one may simultaneously contain resistance genes for several types of antibiotics. Moellering is concerned that such resistance genes could be acquired by Staphylococcus aureus, bacteria that cause virulent infections in the heart and in wounds. Strains of "staph aureus" are already resistant to most conventional antibiotics. Additional resistance genes could make this microbe almost impossible to treat.

"Another example right now is gonorrhea," Moellering says. "For many years, it was treatable with penicillin--pennies a day. We now have so much penicillin-resistant gonorrhea in this country that the Centers for Disease Control recommends using ceftriaxone, a much more expensive drug that must be given by injection. First-line therapy now costs several dollars a day."

The problem is that we have a tendency to look at antibiotics in the same erroneous way we see vitamins--there's nothing to lose, so why not take them? If a friend has a nagging cough, we'll dose her with an old antibiotic out of the medicine chest. If a child starts scratching an ear, we give him some of the antibiotic left over from the last visit to the pharmacy. Probably the least supervised use of antibiotics occurs in livestock farms all over the country, where antibiotics are routinely used to increase weight gain in cattle and pigs.

But, whether we realize it or not, there is a price to pay for all this medication. The more frequently microbes encounter antibiotics, the more likely they are to develop resistance. Right now, the number one reason for antibiotic use in this country is otitis media, inflammation of the middle ear. Doctors write more than 23 million antibiotic prescriptions each year for kids with earaches. As expected, Moellering has begun hearing reports of antibiotic-resistant otitis media infections, particularly in Texas, Kentucky, and Tennessee. These infections are caused by pneumococci that resist not just penicillin, but tetracycline, erythromycin, and a host of other oral agents that could be used as alternative therapy for otitis media.

"They're turning to new agents already," Moellering says. "There are now trials in children of a class of oral antibiotics called quinolones. Quinolones had never been tested before in children, because it was suspected these drugs might cause developmental problems. Now the FDA has decided that it's worthwhile to see whether we can use them to treat otitis media in children."

Ironically, most ear infections probably don't even require treatment, according to Moellering. Nor do the vast majority of upper respiratory infections, he says; colds, flus, bronchitis, and sinusitis are almost always caused by viruses, which are indifferent to antibiotics. And yet 17 million antibiotic prescriptions are written each year for people with these ailments.

Why do doctors give drugs to patients who don't need them? Physicians say patients feel slighted when they come away from an office visit without a prescription, and tend to keep looking until they find someone who will write one. Some surveys do indicate that patients will accept the doctor's decision to eschew antibiotic treatment--if they receive a good explanation. The problem, as Moellering points out, is that "it takes less time to hand out a prescription than to explain why one isn't needed. There's a big educational campaign still needed for doctors and patients."

"Even in situations where there's a minimal chance that they'll help, patients, just like doctors, are tempted to use antibiotics," he says. "They seem to be harmless, and they might do some good, right? But there's much more to it than that. Parents should know that every time we needlessly take antibiotics, we add to the overall pressure that leads to antibiotic resistance. This is particularly important in situations like day care, where kids are in close proximity, sharing a lot of secretions and bacteria.This is where you'll find resistant organisms, and where they can be much more difficult to treat."

The problem of resistance is further compounded by a dearth of new drugs. Two years ago, Moellering was in his last year as editor-in-chief of the journal Antimicrobial Agents and Chemotherapy. Normally, the journal published a review of all the new antibiotics that had come to market during the year. In 1994, there was nothing to say: no new antibacterial agents had been introduced--for the first time in Moellering's 10 years as editor.

"Clearly, we're in danger of entering the twenty-first century with a diminished armamentarium for treating infectious disease," he says. "We're not in danger of having everyone in the world overwhelmed by antibiotic-resistant organisms, but if we continue on the course that we're on, we'll be at the point where we'll see more infections that are very difficult to treat.

"Now, I'm relatively confident that we'll find new drugs to fight bacteria. But we've got to educate people in how to use antibiotics, and slow the spread of resistance, or we'll lose all the advantages that we've gained in treating bacterial infections. People are working hard on this, but if we don't get solutions there's real potential for disaster."

Antibiotic resistance is a complex, global problem, but there are at least some situations where individuals can make a difference. While we were at my sister's house recently, my son was crying and pulling at his ear. "How about a slug of amoxycillin?" my sister offered. "We've got some in the refrigerator."

"No, thanks," I said. "Why don't we save it for a time when we're sure we need it?"

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