Daniel M. Keller, PhD

September 23, 2011

September 23, 2011 (Chicago, Illinois) — Despite the introduction of pediatric vaccines with greater coverage of Streptococcus pneumoniae serotypes, a large proportion of bacterial isolates (56.2% in 2010) are serotypes not covered by the latest 13-valent vaccine, researchers announced here at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy.

An increasing number of isolates are serotypes unrelated to the vaccine types, lead investigator Michael Jacobs, MD, PhD, professor of pathology and medicine and director of microbiology at Case Western Reserve University and University Hospitals Case Medical Center (UHCMC) in Cleveland, Ohio, told delegates during a poster session.

Dr. Michael Jacobs

In 2000, a 7-valent pneumococcal conjugate vaccine (PCV) was introduced for use in children. This PCV-7 contained the capsular polysaccharides of the 7 serotypes most commonly responsible for invasive disease at the time. Since then, the incidence of disease with the vaccine serotypes decreased in all age groups, but other serotypes not covered emerged, particularly the multidrug-resistant 19A and 6A. These are now included in the 13-valent PCV-13, which was introduced in 2010.

Dr. Jacobs has been tracking S pneumoniae serotypes and antibiotic susceptibility for more than 3 decades. For this study, he compared the incidence of serotypes at baseline (1999) and after the introduction of the PCV-7 and PCV-13 vaccines. From January 1999 to December 2010, 1612 S pneumoniae isolates were collected and serotyped at UHCMC.

After the introduction of PCV-7 in 2000, there was a rapid decrease in the number of isolates, which remained stable until 2004, when the annual incidence increased until 2008.

Less than 5% of isolates are vaccine serotypes, despite an increasing trend in the number of isolates. Invasive isolates (bloodstream or cerebrospinal fluid) in adults and children have steadily decreased since 1999, mostly driven by a decrease in the types covered by the vaccines.

Isolates of PCV-13 serotypes began to decrease in 2010, especially 19A isolates. Dr. Jacobs noted that 19A previously accounted for up to one third of isolates, but in 2010, it accounted for less than one quarter.

"I was surprised at how quickly we saw a change after the 13-valent vaccine came out. It only came out in March 2010, and already in 2010 there's a dramatic difference," Dr. Jacobs noted.

The investigators reported that drug resistance, especially to multiple antibiotics, remains a concern, although susceptibility appears to have been rising over the past few years and invasiveness appears to have been falling. They will be looking out for the emergence of replacement serotypes as the new PCV-13 vaccine takes hold.

Dr. Jacobs told Medscape Medical News that 93 serotypes have been identified so far, and the bacterium keeps evolving. "I think the changes we're going to see from now on are not going to be as dramatic as they were in the past, in terms of replacement serotypes taking over the gap," he said. "But the pneumococcus always surprises us. Every prediction I've ever made about S pneumoniae since 1977 has been wrong, and that's how long I've been working on it."

All components of the vaccines up to now have been directed against the capsular polysaccharides of the individual serotypes. Dr. Jacobs said that there are some potential vaccine targets that are more conserved among different serotypes, and several studies are looking into using them to try to develop a more universal vaccine.

David Hooper, MD, chief of the infection control unit and associate chief of the infectious disease division at Massachusetts General Hospital in Boston, and president of the American Society of Microbiology, told Medscape Medical News that what was particularly beneficial about the PCV-7 vaccine was that many of the serotypes that were covered were the ones that were most likely to have resistance to penicillins and other drugs. "Resistance, in fact, did come down associated with that. Some of the strain replacements that have gradually occurred over time have not necessarily had resistance associated with them, but others have," he said.

Strain replacement will probably continue to occur, even with the broader-coverage vaccine. These newer strains, perhaps initially less virulent, "could over time acquire virulence traits," Dr. Hooper predicted. "I don't think there's ever a circumstance where we can declare victory and go home."

The study received no outside funding. Dr. Jacobs reports receiving research grant support and consulting fees as a scientific advisor from Pfizer Vaccines. Dr. Hooper has disclosed no relevant financial relationships.

51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract G3-773. Presented September 18, 2011.

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