Breaking the Antibiotic Habit: A Parent's Guide to Coughs, Colds, Ear Infections, and Sore Throats

First Chapter

Paul A. Offit, M. D., Bonnie Fass-Offit, M. D., and Louis M. Bell, M. D
ISBN 0- 471- 31982-1

Chapter 1
The Promise and Problems of Antibiotics

Deadly Diseases Caused by Bacteria That Resist Antibiotics
Bacteria are now, more than ever before, resisting the killing effects of antibiotics. Bacteria that resist antibiotics (or "superbugs") are harmful to children for a number of reasons.

When a child is infected with a bacterium that resists some antibiotics, other antibiotics must be used to take their place. These other antibiotics are invariably more expensive and only a limited number are available. Sometimes these other antibiotics must be given intravenously in the hospital.

When a child is infected with a bacterium that resists all antibiotics, it may be impossible to treat the infection successfully.

In this chapter we will talk about the serious and some-times deadly infections caused by bacteria that resist antibiotics.

The Most Common Bacterial Infection of Children
One bacterium is the most common cause of bacterial infections in children. It is the most common cause of ear infections, the most common cause of sinus infections, the most common cause of bacterial pneumonia, and the most common cause of bacterial meningitis. The name of this bacterium is Streptococ-cus pneumoniae.
Over the past ten years Streptococcus pneumoniae has become progressively more resistant to antibiotics. Some children have died or been left permanently disabled by infections caused by resistant strains of this bacterium. The crisis of resistant Streptococcus pneumoniae has prompted both the American Academy of Pediatrics and the Centers for Disease Control and Prevention to launch a national campaign to educate parents and doctors about the problem. Infection caused by resistant Streptococcus pneumoniae is the reason we are writing this book.
Although the number of infections caused by resistant Streptococcus pneumoniae have increased dramatically over the past ten years, their emergence could have been predicted by something that happened about twenty-five years ago.

The Ghost of Bacteria Past
One bacterium used to cause two very severe infections in children- meningitis (an infection of the lining of the brain) and sepsis (an infection of the bloodstream). The name of the bacterium was Haemophilus influenza type b (Hib). Before 1990, Hib caused about 20,000 serious infections in children every year. Many children died or were left permanently disabled by infections with Hib. Permanent disabilities included blindness, deafness, mental retardation, and paralysis. Although a devastating and feared infection, Hib was, at one time, always sensitive to (meaning killed by) an antibiotic called ampicillin (an antibiotic almost identical to amoxicillin). Ampicillin, like amoxicillin today, was the most widely prescribed antibiotic for children.
In the 1960s and early 1970s all children admitted to the hospital with meningitis were treated with ampicillin. But in 1974 the first strains of Hib that resisted the killing effects of ampicillin were reported. Doctors found out about the existence of resistant Hib the hard way.

A one-year-old boy was admitted to a county hospital in Maryland on December fourteenth, 1973. He had been vomiting for about one day and had a fever of 104° F. When he was admitted to the hospital, the doctors took a sample of his blood to test for the presence of bacteria. The next day the bacterium Haemophilus influenzae type b (Hib) was found in the blood. The doctors also performed a spinal tap to see if the fluid that bathes the lining of the brain and spinal cord contained bacteria. They found that the spinal fluid contained pus as well as Hib. The boy was started on ampicillin intravenously. The doctors chose ampicillin because before 1973 all Hib bacteria were killed by ampicillin. But the following day the doctors received bad news. The strain of Hib that was infecting this patient was resistant to ampicillin. Quickly they stopped the ampicillin and began treatment with another antibiotic, chloramphenicol. Unfortunately, it was too late. The boy began to have seizures and he soon died. The delay in treatment with effective antibiotics had allowed the bacteria to grow unchecked.

In 1973 children with bacterial infections such as ear infections, sinus infections, or pneumonia were usually treated with ampicillin. Ampicillin was used because it was effective at killing the most common cause of these infections, Streptococ-cus pneumoniae. Hib was not a common cause of any of these infections. But the widespread use of ampicillin in many children caused the emergence of strains of Hib that were resistant to ampicillin. When doctors read about this little boy in the Journal of the American Medical Association, they changed the way that they treated bacterial meningitis, and used the antibiotic chloramphenicol.
By the early 1980s several strains of Hib were discovered that were resistant to both ampicillin and chloramphenicol. So doctors again changed the way that they treated children with meningitis. Now these children were given one of a different group of antibiotics (called cephalosporins) instead of ampicillin or chloramphenicol. Although Hib was becoming progressively more difficult to treat, there were still several other effective drugs available.
The story of Hib changed dramatically in 1990 with the development of a successful Hib vaccine. Six years after the Hib vaccine was first given to children in this country, the number of children with Hib meningitis and sepsis decreased from 20,000 cases each year to less than 100. However, with Strep-tococcus pneumoniae, we may not be as fortunate.

The Ghost of Bacteria Present
In varied and frightening ways the story of Streptococcus pneumonia is different from Hib.
In 1942, when penicillin was first used in the United States, every strain of Streptococcus pneumoniae found to cause disease was killed by penicillin. By the early 1960s, infrequent strains of Streptococcus pneumoniae that resisted the killing effects of penicillin were found. At the time this was not a cause for much concern. These strains were uncommon and rarely caused disease. And soon another class of antibiotics was discovered that effectively killed this bacterium- the cephalosporins.
By the mid-1980s, strains of Streptococcus pneumoniae were found that also resisted killing by the cephalosporins. The emergence of strains that were resistant to penicillins and cephalo-sporins changed the way that doctors treated these infections. From that point onward almost all children with meningitis were treated with an antibiotic called vancomycin. The frightening difference between Hib and Streptococcus pneumoniae is that, al-though there were several antibiotics available to treat highly resistant Hib, vancomycin may be the only available antibiotic to treat strains of Streptococcus pneumoniae that are highly resistant.
Another important difference between Hib and Strepto-coccus pneumoniae is that researchers were able to develop a vaccine to effectively prevent Hib infections, but haven't yet been able to develop a vaccine as effective to prevent infections with Streptococcus pneumoniae. It is easier to make a Hib vaccine because only one type of Hib commonly caused disease in children (type b), but at least ninety types of Streptococcus pneumoniae cause disease. Currently researchers have included as many as eleven of the ninety types in a vaccine. Al-though developing a successful vaccine to prevent Streptococ-cus pneumoniae infections will be difficult, recent studies show promise. An effective vaccine may provide some relief from infections caused by resistant strains of this bacterium.
Now doctors are forced to consider the use of vancomycin on all children with meningitis- so, many children are now receiving vancomycin. Widespread vancomycin use in hospitals poses an enormous risk that Streptococcus pneumoniae will be-come resistant to this drug. As of the writing of this book this hasn't happened. However, there is good reason to believe that it will.
What would happen if Streptococcus pneumoniae became resistant to vancomycin? The first strains of Streptococcus pneumoniae found to resist all antibiotics would appear in hospitals. Next the bacteria would spread from hospitals to surrounding communities. This sequence of events has happened with practically every other strain of bacteria found to resist antibiotics during the past fifty years (see chapter three for more details). Should strains of resistant Streptococcus pneumoniae spread in the community the results could be devastating. Based on the current incidence of diseases caused by Strepto-coccus pneumoniae, each year approximately 7,000 children could die and 1,000 children could be left permanently dam-aged by meningitis, 3,000 children could die from sepsis, and 5,000 children could die from pneumonia.
The prospect of strains of Streptococcus pneumoniae that resist all antibiotics is frightening. But before we devise ways to avoid this crisis, we must first figure out which children are at greatest risk of infection by strains of Streptococcus pneumoniae that are resistant to some antibiotics. Several studies found that there are six common characteristics of children most likely to be infected by resistant Streptococcus pneumoniae. These characteristics would probably surprise many parents:

Race: White
Age: Less than six years
History: Received an antibiotic within the past 3 months
Attends child-care
Lives in the suburbs
Parents with high incomes

The reason these children are at greater risk is that they are more likely to visit a doctor when they are sick. Normally we think of that as a good thing, but every time a child visits a doctor there is a chance of receiving an antibiotic.
In Part II of this book, we will show how curbing antibiotic overuse can dramatically decrease the number of children infected by bacteria that resist antibiotics.

The Ghost of Bacteria Future
A disaster that occurred in Central Africa in November of 1979 was a warning of a future without effective antibiotics. The bacterium that caused this event was named Shigella dysenteriae. Shigella infects the intestine and can cause high fever and diarrhea. However, unlike most other causes of diarrhea, shigella is so harmful to the intestines that the diarrhea is often very bloody. At least 20,000 cases of shigella infection occur in the United States every year. The infection is rarely fatal. People in the United States don't die from shigella infection be-cause a number of antibiotics effectively kill the bacteria (such as ampicillin, chloramphenicol, and sulfonamides).
In November of 1979 an outbreak of shigella occurred in Zaire and spread rapidly from village to village. The bacteria that caused this outbreak were resistant to ampicillin, chloramphenicol, sulfonamides, and tetracycline. Fortunately, the bacteria were sensitive to two other antibiotics (trimethoprim and nalidixic acid). Health officials quickly began treatment with trimethoprim, but by 1981 the bacteria were resistant to that agent, too. By the end of 1981 the epidemic had spread about 200 miles south toward the border between Zaire and Uganda and by then only one effective antibiotic was available- nalidixic acid. So doctors began using nalidixic acid to treat their patients. In 1982 the first strains of bacteria that were resistant to nalidixic acid were found, and by 1985, 35 percent of all shigella strains were resistant to all known antibiotics. The outbreak was brought under control, in large part, by quarantining and other infection control measures. When the outbreak was finally under control, hundreds of thousands of people had been infected with highly resistant shigella, and thousands of children had died.

Could What Happened in Africa Happen Here?
Bacteria that are resistant to antibiotics are actually very common in developing countries. This is because, unlike in the United States, antibiotics can be purchased in developing countries without a prescription. But recently there has been a dramatic increase in the number of bacteria that are resistant to antibiotics in the United States. This increase has occurred for the same reason that explains the high frequency of resistant bacteria in developing countries- antibiotics are overused. Over the past decade there has been almost a 30 percent increase in the number of antibiotic prescriptions written by doctors. It would be interesting to determine how many parents who re-quest an antibiotic actually get one, whether the child really needs it or not. We suspect that the number would be alarmingly high (see chapters eleven and twelve for more details).
In a sense, antibiotics in the United States, as in developing countries, are available upon request.