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Drug-Resistant 19A Serotype Causes Nearly Half of All Pediatric Invasive Pneumococcal Disease Cases

Posted Oct 14 2009 10:02pm
From Medscape Medical News
Barbara Boughton

September 22, 2009 (San Francisco, California) — An investigational 13-valent pneumococcal conjugate vaccine manufactured by Wyeth, currently under review by the US Food and Drug Administration (FDA), should help eliminate newly emerging drug-resistant pneumococcal strains.

Despite the success of the pediatric 7-valent pneumococcal conjugate vaccine (Prevnar, Wyeth) that was introduced in 2000, drug-resistant pneumococcal strains — particularly the 19A serotype — have emerged and threaten the health of some children, particularly those 2 to 4 years of age with underlying health conditions. These children might benefit from catch-up immunizations with the 13-valent vaccine, pending approval, according to 2 teams of researchers here at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

"We are at the point where we've already reduced 80% of the disease burden," said Pekka Nuorti, MD, DSc, from the Respiratory Disease Branch of the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, which sponsored one of the studies. "But we wanted to see how much of the remaining disease is vaccine-preventable."

In their study, the CDC researchers assessed the number of cases of invasive pneumococcal disease (IPD) in 2007 and identified the isolates from these cases.

They found that 64% of the estimated 5040 cases of IPD were caused by serotypes targeted by the new 13-valent vaccine, whereas only 2% were caused by serotypes contained in the currently used vaccine. Serotype 19A accounted for 42% of cases.

The 13-valent vaccine "has the potential to substantially reduce the remaining [pneumococcal] disease burden," Dr. Nuorti said in an interview with Medscape Infectious Diseases. "It looks like there might be some groups that might benefit from a catch-up immunization — including older children with underlying medical conditions."When it makes its recommendations for the vaccine, the CDC will also consider a catch-up vaccination strategy for all children 2 to 4 years of age to extend the vaccine's protection to unvaccinated groups, he said. The vaccine is expected to be licensed by the FDA later this year or early next year.

In another study presented here at the ICAAC, researchers from University Hospitals Case Medical Center in Cleveland, Ohio assessed isolates from 171 cases of Streptococcus pneumonias at their institution in 2008.

Nonvaccine serotypes predominated, and 19A was the most commonly isolated serotype, accounting for about a third of all cases.

"There's been an incredible increase in nonvaccine serotypes and most of that increase is due to 19A," said lead researcher Michael R Jacobs, MD, PhD, director of pathology and medicine at Case Western Reserve University in Cleveland. "No one really predicted this when the [7-valent] vaccine was first introduced," Dr. Jacobs said in an interview with Medscape Infectious Diseases. "Some scientists hypothesized that serotype 19F, which is contained in the 7-valent vaccine, might provide cross-protection against 19A, but that hasn't proved to be the case," Dr. Jacobs added.

In the Cleveland study, most of the nonvaccine isolates, particularly 19A, were resistant to many antibiotics, including penicillin, amoxicillin, ceftriaxone, azithromycin, and clindamycin. "This [increase in nonvaccine isolates] may well represent a trend of replacement serotypes and increasing invasiveness and drug nonsusceptibility, and bears careful watching," the authors conclude in their study.

Although agreeing that the 7-valent vaccine has reduced the morbidity and mortality burden from pneumococcal disease, other researchers consider the growth in drug-resistant replacement serotypes a concern.

"The routine use of hepavalent pneumococcal vaccine [PCV 7] has substantially reduced the rate of invasive pneumococcal disease in children and in the general population," said Luke Chen, MBBS, FRACP, assistant professor of medicine in the Division of Infectious Diseases at Duke University Medical Center in Durham, North Carolina. "However, many investigators have also described an increase in the rate of IPDs caused by serotypes of pneumococci that were not included in PCV 7 — a phenomenon known as 'serotype replacement'," Dr. Chen said.

"The evolving epidemiology of pneumococci is of interest because some nonvaccine serotype pneumococci, such as 19A, are associated with increasing antimicrobial resistance. Other nonvaccine serotypes, such as serotypes 1 and 5, are associated with higher rates of invasive pulmonary disease, such as empyemas and parapneumonic effusions," Dr. Chen added.

The results of the Cleveland study presented by Dr. Jacobs and colleagues are alarming because more than 70% of all serotype 19A isolates were not susceptible to penicillin or ceftriaxone, according to Dr. Chen. "It remains unclear, however, whether the emergence of non-PCV 7 serotype pneumococci and increasing antimicrobial resistance are associated with excess mortality or morbidity," he added.

The CDC study's data are interesting because they project a substantial and further reduction in the overall rates of IPD after transitioning from PCV 7 to a 13-valent pneumococcal vaccine, Dr. Chen said. "PCV 13 may also reduce the incidence of serotypes that are associated with increasing antimicrobial resistance, such as 19A," he added.

Dr. Nuorti, Dr. Jacobs, and Dr. Chen have disclosed no relevant financial relationships.

49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstracts G1-1554 and G1-1536. Presented September 14, 2009.
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