The problem of increasing antibiotic resistance in cases of Streptococcus pneumoniae, a major cause of pneumonia, meningitis and sepsis, was dramatically reversed following the licensing and use of a new conjugate vaccine for young children in February 2000, according to research conducted at Emory University, the Atlanta Veterans Affairs Medical Center, the Centers for Disease Control and Prevention, and the Georgia Division of Public Health. The researchers also found a significant decrease in the incidence of invasive pneumococcal disease in both vaccinated children and unvaccinated adults after the vaccine was introduced.
The research, led by David S. Stephens, MD, professor and vice chair of medicine and division director of infectious diseases in Emory University School of Medicine, was published in the March 5, 2005 issue of The Lancet.
Following approval of the seven-valent pneumococcal conjugate vaccine for young children in the U.S. in February 2000, the vaccine was in general use in Atlanta by the end of 2000. Antibiotic resistance in pneumonia, after increasing steadily in Atlanta from 4.5 per 100,000 in 1994 to 9.3 per 100,000 in 1999 (more than 25 percent of invasive pneumococcal isolates), fell to 2.9 per 100,000 by 2002. The incidence of invasive pneumonia in Atlanta fell from a mean annual incidence of 30.2 per 100,000 in the period January 1994 to December 1999 to 13.1 per 100,000 in 2002.
The most striking reductions in invasive pneumococcal disease were in the youngest children, which also was the age group targeted to receive the vaccine. Children younger than two years old experienced an 82 percent decrease in invasive disease, and children two to four years old had a 71 percent decrease.
In addition to declining rates of pneumonia in young children, the researchers also found significant drops in adults aged 20-39 (54 percent), 40-64 (25 percent) and 65 and older (39 percent) who did not receive vaccine, an effect known as "herd immunity."
Increases in antibiotic resistance by S. pneumoniae are also a problem in other parts of the U.S., Canada, Europe, Africa and Asia. Resistance increased dramatically after the introduction and widespread use of new macrolide antibiotics such as azithromycin and clarithromycin, especially in children younger than five years.
The Atlanta research team studied pneumococcal isolates and demographic data from patients with invasive disease. They calculated cumulative incidence rates for invasive pneumonia from 1994 to 2002 using population estimates and census data from the U.S. Census Bureau.
The decline in invasive pneumococcal disease and in macrolide resistance occurred even though there were substantial shortages of the childhood vaccine between 2001 and 2003.
"The decline in antibiotic resistance in invasive pneumococci in Atlanta between 2000 and 2002 was the result of introducing the pneumococcal conjugate vaccine," says Dr. Stephens. "The vaccine had both direct and herd immunity effects as shown by the striking decline in disease incidence in children under five years, as well as in adults who were not vaccinated."
Other possible explanations for the reductions in invasive disease and antibiotic resistance were not convincing, Dr. Stephens notes. "Our study showed just how quickly vaccines can become effective in overcoming antibiotic resistance, but also just how quickly antibiotic resistance can spread when antibiotics are used inappropriately. It will be important to continue combining vaccines with programs that emphasize appropriate use of antibiotics."