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HIGHLIGHTS: According to a Cedars-Sinai Medical Center scientist, controlling antibiotic usage in an outpatient setting to prevent further increases in the rate of antibiotic resistance is now a national priority. Streptococcus pneumoniae, bacteria that can cause life-threatening infections in adults and especially children, are rapidly becoming resistant to the most widely used antibiotics currently available to treat bacterial infections, says Moshe Arditi, M.D.. Dr. Arditi is the author of an article in the November issue of Pediatrics and director of Cedars-Sinai Medical Center's Division of Pediatric Infectious Diseases.

AVAILABLE FOR INTERVIEWS: Moshe Arditi, M.D., Director, Cedars-Sinai Medical Center Division of Pediatric Infectious Diseases

BACTERIA BECOMING INCREASINGLY RESISTANT TO ANTIBIOTICS, BUT NEW VACCINES ARE ON THE HORIZON

LOS ANGELES (January 11, 1998) -- Streptococcus pneumoniae, bacteria that can cause life-threatening infections in adults and especially children, are rapidly becoming resistant to penicillin and cephalosporins such as ceftriaxone, the most widely used antibiotics currently available to treat bacterial infections, according to Moshe Arditi, M.D., author of an article in the November issue of Pediatrics and director of Cedars-Sinai Medical Center's Division of Pediatric Infectious Diseases.

Dr. Arditi said that while the bacteria are becoming resistant to antibiotics at "an astonishing rate," the penicillin-resistant strains of Streptococcus pneumoniae, or pneumococci, obtained from children with meningitis do not appear to be more virulent, or severe, than those that are susceptible to penicillin -- at least for now.

The Pediatrics article describes a three-year study of children suffering from pneumococcal meningitis. Researchers reviewed the charts of 180 children who were admitted to eight different children's hospitals between September 1, 1993 and August 31, 1996. Because one child had two episodes of infection, 181 episodes were documented in the findings. Dr. Arditi said the study looked at the clinical presentation, hospital course and outcome, taking into consideration the antibiotic resistance patterns of the pneumococci causing the infection. Researchers then determined whether there was a difference in outcome if the infecting organism was an antibiotic-resistant strain of pneumococcus.

"If you look at each year of the three-year study and look at the percentages, you see a dramatic increase in antibiotic resistance between the second year, for example, and the third year," said Dr. Arditi. "In the second year, the penicillin non-susceptible rate (intermediate susceptible and resistant organisms) was 13 percent. In the third year of the study, it jumped to 27 percent. For ceftriaxone, resistance in the first year was 1.7 percent. In the second year, it became 5 percent. In the third year, it jumped to 15 percent. In other words, resistance to ceftriaxone tripled between the second and the third year of the study."

The rapid increase in resistance is also obvious when looking at the recent history of penicillin use. For example, 27 percent of the pneumococci were not susceptible to penicillin in the final year of this study, 1996. That compares to 0.02 percent reported less than a decade ago, according to Dr. Arditi.

Many "varieties," or serological types, of pneumococci exist. The bacteria can cause pneumonia and many other infections, such as sinusitis and infection of the middle ear. In fact, they are the most common cause of acute middle ear infections and invasive bacterial infections -- including pneumonia and meningitis -- in children, according to Dr.Arditi. They also cause more than 500,000 cases of pneumonia in adults and children each year, and are one of the most common causes of bacterial meningitis in young children, resulting in approximately 5,000 cases of meningitis each year.

This study focused specifically on children with pneumococcal meningitis and is likely the largest study of its kind. Bacterial meningitis -- a bacterial infection of the meninges, the membranes that envelop the brain and spinal cord -- can cause death or permanent neurologic damage. In fact, of the 180 children in this study, 14 died. Of those who survived, 25 percent developed neurologic problems and 32 percent suffered moderate to severe hearing loss.

The study of pneumococcal meningitis was part of a larger study of pneumococcal infections among children in general. Those results were published in the September 1998 issue of Pediatrics. The research was conducted at eight children's hospitals in the United States and looked at 1,291 episodes of invasive pneumococcal infection in 1,255 children.

"In the past several years in the United States as well as worldwide, the pneumococcal isolates that are resistant to antibiotics have been increasing in frequency -- dramatically. Not only the frequency is increasing but the degree of resistance also is consistently becoming greater," according to Dr. Arditi. He said there is concern that clinical outcomes may decline as more strains of bacteria become increasingly resistant.

But there is hope in the near future, in the form of new vaccines against pneumococcus, said Dr. Arditi. In fact, pneumococcal polysaccharide vaccines -- which use a carbohydrate from the cells of the bacteria to provide immunity -- have been developed and are in use. However, while safe and effective for adult use, they have not worked well in protecting young children, especially those younger than two years of age. But newer vaccines -- multivalent pneumococcal conjugate vaccines -- combine vaccines against several strains of pneumococcus and attach a carrier protein.

"Infants and young children respond much better to these vaccines because of the carrier protein attached to the polysaccharide," said Dr. Arditi. He said details of the latest stages of clinical trials have started to become available and will probably be completed early in 1999. Preliminary reports indicate that the vaccines will be highly efficient in protecting those who are most vulnerable to these infections: infants and young children. A vaccine introduced 10 years ago had a major impact on what was then the most common cause of bacterial meningitis, Haemophilus influenzae type B (Hib). "Since the Hib vaccine was introduced in 1989 and led to a dramatic decline in the incidence of Haemophilus influenzae meningitis, proportionally, Streptococcus pneumoniae has become the most common cause of morbidity and mortality resulting from bacterial meningitis. It also has become the most common cause of bacterial meningitis in children 1 to 23 months of age in the!

United States."

"It's absolutely necessary to educate the public and practitioners regarding this problem and the contributing factors," Dr. Arditi said. "I think controlling antibiotic usage in an outpatient setting to prevent further increases in the rate of antibiotic resistance is now a national priority."

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