Change in serotypes does not mean change in therapy for AOM – at least not yet

NEW YORK CITY — The conjugate pneumococcal vaccine (PCV7, Prevnar, Wyeth) will likely reduce colonization of drug-resistant Streptococcus pneumoniae, Stephen I. Pelton, MD, said here at the Infectious Diseases in Children Symposium.

Whether this will change therapeutic management of diseases like acute otitis media (AOM) is not known, but it might lead to using narrow-spectrum antibiotics for treatment of AOM caused by S. pneumoniae, the leading cause of otitis. At the moment, there should be no change in treatment, he said, but experts are tracking this change in epidemiology.

“We’re going to see a decline in the total amount of otitis due to pneumococci. We’re going to see an increase in disease due to non-vaccine serotypes. We’re probably going to see an increase in disease due to Haemophilus and Moraxella and, whether we’ll see other pathogens, such as group A streptococcus, increase or not, I think remains to be answered. And we should see a decrease in antibiotic-resistant pneumococci as a cause of otitis media at least in the short term,” said Pelton, who is professor of pediatrics at Boston University School of Medicine and a member of the Infectious Diseases in Children editorial advisory board.

It is not unusual for nasopharyngeal flora to change. Experts know that antibiotic use changes the flora in the nasopharynx. Children who begin treatment with sensitive organisms can acquire organisms that are no longer sensitive due to the misuse of antibiotics, either by overuse, not finishing the course of treatment or improper prescribing. In addition, these children can share the resistant organisms with other children at day care centers and schools. This frequently occurs during the winter months when children are taking antibiotics for frequent upper respiratory infections.

“This is one of the reasons why I think as time goes on, especially during the respiratory virus season, that you see the accumulation of resistant pathogens in the nasopharynx and it’s why respiratory tract bacterial disease in January, February and March is often more difficult to treat than it is in June, July and August,” he said.

Effect on carriage

PCV7 also affects the carriage of organisms in the nasopharynx. The vaccine is made up of only seven serotypes of S. pneumoniae, but these are the serotypes most likely to cause pneumococcal disease in U.S. children as well as those most likely to be resistant to antibiotics. Pelton and his colleagues in Boston studied the effect of the vaccine on carriage in the community. Before the vaccine was available, 75% of tested children carried a vaccine serotype or a vaccine-related serotype of S. pneumoniae. Two years after the introduction of PCV7, the researchers saw a decline to 54% in the proportion of children colonized with a vaccine or vaccine-related serotype. These have been replaced by an increase in the number of children colonized with non-vaccine serotypes.

“The reason why that’s relevant is because it is not likely that all serotypes of pneumococci will be resistant to antibiotics, especially to multiple drug classes,” he explained. Therefore, if the organism that is likely causing the AOM is not resistant, it will be susceptible to a narrow-spectrum antibiotic like amoxicillin.

A study looking at 500 middle ear isolates found that there was little penicillin resistance in non-vaccine serotypes compared with serotypes covered by the vaccine, he added.

“A shift from vaccine serotypes to non-vaccine serotypes will be a shift away from the isolates that are more likely to be resistant to isolates that are more susceptible to antibiotics,” he said.

The Finnish trial gave 800 children either the conjugate vaccine or a control vaccine and performed tympanocentesis for each episode of AOM. Overall, there was a reduction in disease incidence, Pelton said. There were 414 episodes of pneumococcal otitis in the control group, 271 episodes of pneumococcal otitis in the pneumococcal vaccine group.

“If you look for vaccine serotypes and cross-reactive serotypes, this accounts for about 80% of the pneumococcal episodes in the control group, but it only accounts for slightly more than 50% of the otitis episodes in the vaccine group. So, indeed, there is a shift away from vaccine serotypes in children who get pneumococcal conjugate vaccine,” he said.

Approach to treatment

Still, Pelton said it is too early to change treatment strategies. Some cases of AOM are still caused by Moraxella catarrhalis and Haemophilus influenzae, both beta-lactamase producers. In the Finnish trial, researchers did find a slight increase in cases caused by H. influenzae.

And there is still a significant amount of disease due to S. pneumoniae, even in children who have had PCV7. “So, we cannot get away from the fact that the pneumococcal serotypes in the community that carry resistance markers still continue to produce a significant amount of upper respiratory disease in children who have gotten pneumococcal conjugate vaccine. And it’s for that reason that a child who has been vaccinated cannot, in my mind, be treated differently than a child who has not been vaccinated, at least at this point, because pneumococcal vaccine serotypes still represent a major cause of disease in that population,” he said.

“Although we frequently talk about the microbiology of otitis as a one-size-fits-all, it’s really not,” he said. “Antibiotic therapy and vaccines exert a selective pressure on nasopharyngeal colonization with bacterial otopathogens. The microbiology of acute otitis media in children with recent antibiotic therapy is subtly different in children without prior episodes and prior treatment.”

Although PCV7 is likely to reduce colonization with drug-resistant S. pneumoniae in the short term, the long-term effects are not yet known, he said.

For more information:

• Pelton SI. Selective pressure from antibiotics and vaccine: effect on AOM. Presented at the 15th Annual Infectious Diseases in Children symposium. Nov. 16-17. New York City.
• Eskola J, Kilpi T, Palmu A., et. al. Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N Engl J. Med. 2001;344:403-409.

• Dr. Pelton has research grants from Wyeth, GlaxoSmithKline and Aventis.