Replacement Serotypes Spur Resistance Fears : Despite pneumococcal vaccine successes, penicillin nonsusceptible infections may be increasing again.

ASPEN, COLO. — Although the conjugate heptavalent pneumococcal vaccine has decreased penicillin resistance rates among those serotypes of the bacteria included in the vaccine, there is already some evidence that “replacement” serotypes are appearing.

And among those replacement serotypes, penicillin resistance may be on the increase, Dr. Sheldon Kaplan said at a conference on pediatric infectious diseases sponsored by Children's Hospital, Denver.

This is a situation that deserves watching, said Dr. Kaplan, chief of the infectious disease service at Texas Children's Hospital, Houston.

Two serotypes that seem to be emerging as the more common ones contained in the vaccine decline are serotypes 15 and 33, Dr. Kaplan reported.

According to a pneumococci surveillance project of eight children's hospitals, there was a mean five cases of invasive disease caused by serotype 15 in 1994–2000.

In 2002, there were 14 cases.

For serotype 33, the mean number of cases was less than one during the 1994–2000 period.

In 2002, there were nine cases, said Dr. Kaplan, whose hospital is part of the surveillance project (Pediatrics 2004;113:443–9).

Specific isolates of serotype 15 collected by the project have been found to have the same blot pattern on a pulse-field electrophoresis gel about 60% of the time.

That suggests the different isolates taken from various children are the same clone of the bacteria.

About 80% of the serotype 33 isolates appear to be the same clone.

Serotype 19A also appears to be on the increase, and 19A appears specifically to be a serotype that is replacing 19F, a serotype in the vaccine.

According to one report, the annual incidence rate of invasive disease in children less than 2 years of age caused by serotype 19A has increased from 1 case per 100,000 population in 2001 to more than 6 cases per 100,000 in 2004 (J. Infect. Dis. 2005;192:1988–95).

There also has been a 2.5-fold increase in cases in children older than 5 years of age.

“We're not the only people who are seeing this,” Dr. Kaplan commented. “CDC is actually reporting increases in these serotypes as well.”

Moreover, as is well known, a number of surveys have suggested there has been a decrease in antibiotic resistance since the introduction of the conjugate vaccine.

That was true, but it may not be anymore, Dr. Kaplan said. The rate of penicillin nonsusceptible infections may actually be increasing again.

Although the number of cases caused by serotypes in the vaccine has declined precipitously, the number of cases caused by serotypes not in the vaccine has increased, and those serotypes appear to be acquiring more resistance.

The incidence rate of invasive disease caused by penicillin nonsusceptible pneumococci among children younger than 2 years has increased overall since 2002. And, considering just isolates not in the vaccine, it has increased from 51% in 1999 to 68% in 2004, Dr. Kaplan said.

“It looks like these nonvaccine serotypes are more likely to be penicillin nonsusceptible today than they were 5 years ago,” he said.

In addition, a group from Salt Lake City has seen an increase in pediatric cases of pneumococcal pneumonia complicated with empyema since the introduction of the vaccine. Moreover, the serotypes associated with these cases tend to be those not in the vaccine—serotypes 1, 3, and 19A.

The Salt Lake City group reported that for the 4 years prior to the vaccine, their medical center saw an average of 38 cases of empyema, compared with an average of 72 cases in the first 4 years after the vaccine's introduction.

Also, pneumococcal parapneumonic empyema represented only 17% of the cases of identified invasive pneumococcal disease seen at that center in the years prior to the vaccine, but 32% of the cases after the vaccine (Pediatr. Infect. Dis. J. 2006;25:250–4).

Serotype 1 was the most common serotype associated with the empyema both prior to the vaccine (46%) and afterward (34%). Serotypes 3 and 19A became common after the vaccine (20% and 14%, respectively).

“I can't explain this, but they are clearly seeing more cases, with more nonvaccine types,” Dr. Kaplan said.

He noted that the vaccine may have to be updated with at least some of these emerging strains.

“We do see these emerging serotypes. How we will address that down the road will have to be seen,” Dr. Kaplan added. “It is an expensive vaccine.”

'We're not the only people who are seeing this. CDC is actually reporting increases.' DR. KAPLAN

ASPEN, COLO. — Although the conjugate heptavalent pneumococcal vaccine has decreased penicillin resistance rates among those serotypes of the bacteria included in the vaccine, there is already some evidence that “replacement” serotypes are appearing.

And among those replacement serotypes, penicillin resistance may be on the increase, Dr. Sheldon Kaplan said at a conference on pediatric infectious diseases sponsored by Children's Hospital, Denver.

This is a situation that deserves watching, said Dr. Kaplan, chief of the infectious disease service at Texas Children's Hospital, Houston.

Two serotypes that seem to be emerging as the more common ones contained in the vaccine decline are serotypes 15 and 33, Dr. Kaplan reported.

According to a pneumococci surveillance project of eight children's hospitals, there was a mean five cases of invasive disease caused by serotype 15 in 1994–2000.

In 2002, there were 14 cases.

For serotype 33, the mean number of cases was less than one during the 1994–2000 period.

In 2002, there were nine cases, said Dr. Kaplan, whose hospital is part of the surveillance project (Pediatrics 2004;113:443–9).

Specific isolates of serotype 15 collected by the project have been found to have the same blot pattern on a pulse-field electrophoresis gel about 60% of the time.

That suggests the different isolates taken from various children are the same clone of the bacteria.

About 80% of the serotype 33 isolates appear to be the same clone.

Serotype 19A also appears to be on the increase, and 19A appears specifically to be a serotype that is replacing 19F, a serotype in the vaccine.

According to one report, the annual incidence rate of invasive disease in children less than 2 years of age caused by serotype 19A has increased from 1 case per 100,000 population in 2001 to more than 6 cases per 100,000 in 2004 (J. Infect. Dis. 2005;192:1988–95).

There also has been a 2.5-fold increase in cases in children older than 5 years of age.

“We're not the only people who are seeing this,” Dr. Kaplan commented. “CDC is actually reporting increases in these serotypes as well.”

Moreover, as is well known, a number of surveys have suggested there has been a decrease in antibiotic resistance since the introduction of the conjugate vaccine.

That was true, but it may not be anymore, Dr. Kaplan said. The rate of penicillin nonsusceptible infections may actually be increasing again.

Although the number of cases caused by serotypes in the vaccine has declined precipitously, the number of cases caused by serotypes not in the vaccine has increased, and those serotypes appear to be acquiring more resistance.

The incidence rate of invasive disease caused by penicillin nonsusceptible pneumococci among children younger than 2 years has increased overall since 2002. And, considering just isolates not in the vaccine, it has increased from 51% in 1999 to 68% in 2004, Dr. Kaplan said.

“It looks like these nonvaccine serotypes are more likely to be penicillin nonsusceptible today than they were 5 years ago,” he said.

In addition, a group from Salt Lake City has seen an increase in pediatric cases of pneumococcal pneumonia complicated with empyema since the introduction of the vaccine. Moreover, the serotypes associated with these cases tend to be those not in the vaccine—serotypes 1, 3, and 19A.

The Salt Lake City group reported that for the 4 years prior to the vaccine, their medical center saw an average of 38 cases of empyema, compared with an average of 72 cases in the first 4 years after the vaccine's introduction.

Also, pneumococcal parapneumonic empyema represented only 17% of the cases of identified invasive pneumococcal disease seen at that center in the years prior to the vaccine, but 32% of the cases after the vaccine (Pediatr. Infect. Dis. J. 2006;25:250–4).

Serotype 1 was the most common serotype associated with the empyema both prior to the vaccine (46%) and afterward (34%). Serotypes 3 and 19A became common after the vaccine (20% and 14%, respectively).

“I can't explain this, but they are clearly seeing more cases, with more nonvaccine types,” Dr. Kaplan said.

He noted that the vaccine may have to be updated with at least some of these emerging strains.

“We do see these emerging serotypes. How we will address that down the road will have to be seen,” Dr. Kaplan added. “It is an expensive vaccine.”

'We're not the only people who are seeing this. CDC is actually reporting increases.' DR. KAPLAN

ASPEN, COLO. — Although the conjugate heptavalent pneumococcal vaccine has decreased penicillin resistance rates among those serotypes of the bacteria included in the vaccine, there is already some evidence that “replacement” serotypes are appearing.

And among those replacement serotypes, penicillin resistance may be on the increase, Dr. Sheldon Kaplan said at a conference on pediatric infectious diseases sponsored by Children's Hospital, Denver.

This is a situation that deserves watching, said Dr. Kaplan, chief of the infectious disease service at Texas Children's Hospital, Houston.

Two serotypes that seem to be emerging as the more common ones contained in the vaccine decline are serotypes 15 and 33, Dr. Kaplan reported.

According to a pneumococci surveillance project of eight children's hospitals, there was a mean five cases of invasive disease caused by serotype 15 in 1994–2000.

In 2002, there were 14 cases.

For serotype 33, the mean number of cases was less than one during the 1994–2000 period.

In 2002, there were nine cases, said Dr. Kaplan, whose hospital is part of the surveillance project (Pediatrics 2004;113:443–9).

Specific isolates of serotype 15 collected by the project have been found to have the same blot pattern on a pulse-field electrophoresis gel about 60% of the time.

That suggests the different isolates taken from various children are the same clone of the bacteria.

About 80% of the serotype 33 isolates appear to be the same clone.

Serotype 19A also appears to be on the increase, and 19A appears specifically to be a serotype that is replacing 19F, a serotype in the vaccine.

According to one report, the annual incidence rate of invasive disease in children less than 2 years of age caused by serotype 19A has increased from 1 case per 100,000 population in 2001 to more than 6 cases per 100,000 in 2004 (J. Infect. Dis. 2005;192:1988–95).

There also has been a 2.5-fold increase in cases in children older than 5 years of age.

“We're not the only people who are seeing this,” Dr. Kaplan commented. “CDC is actually reporting increases in these serotypes as well.”

Moreover, as is well known, a number of surveys have suggested there has been a decrease in antibiotic resistance since the introduction of the conjugate vaccine.

That was true, but it may not be anymore, Dr. Kaplan said. The rate of penicillin nonsusceptible infections may actually be increasing again.

Although the number of cases caused by serotypes in the vaccine has declined precipitously, the number of cases caused by serotypes not in the vaccine has increased, and those serotypes appear to be acquiring more resistance.

The incidence rate of invasive disease caused by penicillin nonsusceptible pneumococci among children younger than 2 years has increased overall since 2002. And, considering just isolates not in the vaccine, it has increased from 51% in 1999 to 68% in 2004, Dr. Kaplan said.

“It looks like these nonvaccine serotypes are more likely to be penicillin nonsusceptible today than they were 5 years ago,” he said.

In addition, a group from Salt Lake City has seen an increase in pediatric cases of pneumococcal pneumonia complicated with empyema since the introduction of the vaccine. Moreover, the serotypes associated with these cases tend to be those not in the vaccine—serotypes 1, 3, and 19A.

The Salt Lake City group reported that for the 4 years prior to the vaccine, their medical center saw an average of 38 cases of empyema, compared with an average of 72 cases in the first 4 years after the vaccine's introduction.

Also, pneumococcal parapneumonic empyema represented only 17% of the cases of identified invasive pneumococcal disease seen at that center in the years prior to the vaccine, but 32% of the cases after the vaccine (Pediatr. Infect. Dis. J. 2006;25:250–4).

Serotype 1 was the most common serotype associated with the empyema both prior to the vaccine (46%) and afterward (34%). Serotypes 3 and 19A became common after the vaccine (20% and 14%, respectively).

“I can't explain this, but they are clearly seeing more cases, with more nonvaccine types,” Dr. Kaplan said.

He noted that the vaccine may have to be updated with at least some of these emerging strains.

“We do see these emerging serotypes. How we will address that down the road will have to be seen,” Dr. Kaplan added. “It is an expensive vaccine.”

'We're not the only people who are seeing this. CDC is actually reporting increases.' DR. KAPLAN