Post-PCV13 findings prompt continued surveillance

PHILADELPHIA – Invasive pneumococcal infections declined by 42% in 2011, compared with 2007-2009, the years after the introduction of the 13-valent pneumococcal conjugate vaccine, according to an analysis of data from eight U.S. children’s hospitals.

Infections continued to decline – by 48% overall – 2-3 years after full implementation of the vaccine. Declines were seen in the rates of bacteremia, pneumonia, and mastoiditis, but the rates of pneumococcal meningitis in the latter years remained unchanged, with an increasing proportion of cases occurring among children with invasive disease.

© Micah Young / istockphoto.com

The most common 13-valent pneumococcal conjugate vaccine (PCV13) serotypes causing invasive pneumococcal infections in 2011 were 19A and 7F. The declines in invasive infections in 2012 and 2013 were mainly because of declines in serotype 19A and 7F isolates, which decreased by 58% and 54%, respectively, but serotype 3 isolates remained at pre-PCV13 levels, Dr. Sheldon L. Kaplan of Baylor College of Medicine and Texas Children’s Hospital, in Houston, reported at an annual scientific meeting on infectious diseases.

“We had 29 children with invasive pneumococcal disease caused by a PCV13 serotype [in 2012-2013]. All but one were a 19A or serotype 3,” he said at thecombined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Nine children with serotype 19A isolates, and 4 with serotype 3 isolates had received at least two doses of PCV13 prior to developing infections. In 2013, 3 of 12 children with 19A isolates had received four PCV13 doses prior to developing serotype 19A infections.

Only three serotype 1-, 7-, and 19F-related invasive infections occurred during the study period, and no serotype 5–related infections occurred.

In 2012-2013, non-PCV13 serotypes – mainly 33F and 22F – accounted for 71% of isolates, Dr. Kaplan said.

Of note, 45% of children at the eight hospitals that are part of the U.S. Pediatric Multicenter Pneumococcal Surveillance Study Group – which has been conducting pneumococcal surveillance since 1993 – had an underlying condition during 2011-2013, compared with 37% in 2007-2009. The difference was statistically significant, Dr. Kaplan said, noting that malignancies were the most common type of underlying condition, followed by central nervous system disorders, genetic disorder, cardiovascular disorders, and renal disorders.

Non-PCV13 serotypes accounted for 78% of isolates from children with underlying conditions, he said.

Mortality was 0.8% (5 of 626) in 2007-2009, and 3.7% (13 of 352) in 2011-2013. Of the 13 children who died in 2011-2013, 10 had a non-PCV13 serotype, and 9 had an underlying condition, Dr. Kaplan said.

Almost all (99%) of non–central nervous system infections in 2011-2013 were susceptible to penicillin and ceftriaxone.

“Continued surveillance is warranted, especially to monitor non-PCV13 serotypes associated with invasive pneumococcal disease,” he said.

As for pneumococcal meningitis, rates decreased significantly after the introduction of PCV7, but the proportion among children with invasive pneumococcal disease increased by 67% over time, accounting for 12% of cases during 2007-2009, compared with 20% of cases during 2011-2013, according to Dr. Liset Olarte, also of Baylor College of Medicine and Texas Children’s Hospital.

The proportion decreased by 21% among children younger than 24 months, but increased significantly in those aged 24 to 59 months, she noted.

Clinical data showed that in 2007-2009, 19A, 7F, and 3 were the most common serotypes associated with pneumococcal meningitis in the eight hospitals in the surveillance study group. In 2011-13, 19A remained the most common serotype, followed by non-PCV13 serotypes 35B and 22F. Overall, non-PCV13 serotypes causing pneumococcal meningitis increased in both number of cases (24 to 49) and proportion of cases (46% to 73%) after PCV13 introduction.

“In our study, only the change in serotype 7F was statistically significant,” said Dr. Olarte.

The proportion of isolates that were non-susceptible to penicillin did not change significantly from 2007-2009 to 2011-2013 (26% and 25%, respectively), but the proportion nonsusceptible to ceftriaxone, and thus requiring vancomycin for treatment, decreased significantly – by 77% – from 13% to 3%.

All of the isolates with a ceftriaxone minimum inhibitory concentration of 1 mcg/mL or greater and penicillin minimum inhibitory concentration of 2 mcg/mL or greater were serotype 19A, Dr. Olarte said.

Mortality did not change significantly during the study period, but there was a marked, significant increase in hemiparesis cases, from 1% to 12%, after introduction of PCV13. However, this increase was not associated with any particular serotype.

Additionally, subdural empyema on neuroimaging increased from 1% to 16%, but was not associated with any particular serotype and was not associated with the cases of hemiparesis.

Overall, 52% of survivors had some sort of neurologic sequelae at the time of discharge, but there were no differences in terms of specific sequelae between the two groups.

The rates of morbidity and mortality for pneumococcal meningitis remain substantial and have not changed significantly since introduction of PCV13, Dr. Olarte said.

However, if the number of cephalosporin nonsusceptible pneumococci isolated from children with meningitis continues to decrease, modification of empiric antibiotic selection for suspected bacterial meningitis might be considered in the future, therefore ongoing surveillance is warranted, she said.

The studies were partially supported by Pfizer. The authors reported having no other disclosures.

PHILADELPHIA – Invasive pneumococcal infections declined by 42% in 2011, compared with 2007-2009, the years after the introduction of the 13-valent pneumococcal conjugate vaccine, according to an analysis of data from eight U.S. children’s hospitals.

Infections continued to decline – by 48% overall – 2-3 years after full implementation of the vaccine. Declines were seen in the rates of bacteremia, pneumonia, and mastoiditis, but the rates of pneumococcal meningitis in the latter years remained unchanged, with an increasing proportion of cases occurring among children with invasive disease.

© Micah Young / istockphoto.com

The most common 13-valent pneumococcal conjugate vaccine (PCV13) serotypes causing invasive pneumococcal infections in 2011 were 19A and 7F. The declines in invasive infections in 2012 and 2013 were mainly because of declines in serotype 19A and 7F isolates, which decreased by 58% and 54%, respectively, but serotype 3 isolates remained at pre-PCV13 levels, Dr. Sheldon L. Kaplan of Baylor College of Medicine and Texas Children’s Hospital, in Houston, reported at an annual scientific meeting on infectious diseases.

“We had 29 children with invasive pneumococcal disease caused by a PCV13 serotype [in 2012-2013]. All but one were a 19A or serotype 3,” he said at thecombined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Nine children with serotype 19A isolates, and 4 with serotype 3 isolates had received at least two doses of PCV13 prior to developing infections. In 2013, 3 of 12 children with 19A isolates had received four PCV13 doses prior to developing serotype 19A infections.

Only three serotype 1-, 7-, and 19F-related invasive infections occurred during the study period, and no serotype 5–related infections occurred.

In 2012-2013, non-PCV13 serotypes – mainly 33F and 22F – accounted for 71% of isolates, Dr. Kaplan said.

Of note, 45% of children at the eight hospitals that are part of the U.S. Pediatric Multicenter Pneumococcal Surveillance Study Group – which has been conducting pneumococcal surveillance since 1993 – had an underlying condition during 2011-2013, compared with 37% in 2007-2009. The difference was statistically significant, Dr. Kaplan said, noting that malignancies were the most common type of underlying condition, followed by central nervous system disorders, genetic disorder, cardiovascular disorders, and renal disorders.

Non-PCV13 serotypes accounted for 78% of isolates from children with underlying conditions, he said.

Mortality was 0.8% (5 of 626) in 2007-2009, and 3.7% (13 of 352) in 2011-2013. Of the 13 children who died in 2011-2013, 10 had a non-PCV13 serotype, and 9 had an underlying condition, Dr. Kaplan said.

Almost all (99%) of non–central nervous system infections in 2011-2013 were susceptible to penicillin and ceftriaxone.

“Continued surveillance is warranted, especially to monitor non-PCV13 serotypes associated with invasive pneumococcal disease,” he said.

As for pneumococcal meningitis, rates decreased significantly after the introduction of PCV7, but the proportion among children with invasive pneumococcal disease increased by 67% over time, accounting for 12% of cases during 2007-2009, compared with 20% of cases during 2011-2013, according to Dr. Liset Olarte, also of Baylor College of Medicine and Texas Children’s Hospital.

The proportion decreased by 21% among children younger than 24 months, but increased significantly in those aged 24 to 59 months, she noted.

Clinical data showed that in 2007-2009, 19A, 7F, and 3 were the most common serotypes associated with pneumococcal meningitis in the eight hospitals in the surveillance study group. In 2011-13, 19A remained the most common serotype, followed by non-PCV13 serotypes 35B and 22F. Overall, non-PCV13 serotypes causing pneumococcal meningitis increased in both number of cases (24 to 49) and proportion of cases (46% to 73%) after PCV13 introduction.

“In our study, only the change in serotype 7F was statistically significant,” said Dr. Olarte.

The proportion of isolates that were non-susceptible to penicillin did not change significantly from 2007-2009 to 2011-2013 (26% and 25%, respectively), but the proportion nonsusceptible to ceftriaxone, and thus requiring vancomycin for treatment, decreased significantly – by 77% – from 13% to 3%.

All of the isolates with a ceftriaxone minimum inhibitory concentration of 1 mcg/mL or greater and penicillin minimum inhibitory concentration of 2 mcg/mL or greater were serotype 19A, Dr. Olarte said.

Mortality did not change significantly during the study period, but there was a marked, significant increase in hemiparesis cases, from 1% to 12%, after introduction of PCV13. However, this increase was not associated with any particular serotype.

Additionally, subdural empyema on neuroimaging increased from 1% to 16%, but was not associated with any particular serotype and was not associated with the cases of hemiparesis.

Overall, 52% of survivors had some sort of neurologic sequelae at the time of discharge, but there were no differences in terms of specific sequelae between the two groups.

The rates of morbidity and mortality for pneumococcal meningitis remain substantial and have not changed significantly since introduction of PCV13, Dr. Olarte said.

However, if the number of cephalosporin nonsusceptible pneumococci isolated from children with meningitis continues to decrease, modification of empiric antibiotic selection for suspected bacterial meningitis might be considered in the future, therefore ongoing surveillance is warranted, she said.

The studies were partially supported by Pfizer. The authors reported having no other disclosures.

PHILADELPHIA – Invasive pneumococcal infections declined by 42% in 2011, compared with 2007-2009, the years after the introduction of the 13-valent pneumococcal conjugate vaccine, according to an analysis of data from eight U.S. children’s hospitals.

Infections continued to decline – by 48% overall – 2-3 years after full implementation of the vaccine. Declines were seen in the rates of bacteremia, pneumonia, and mastoiditis, but the rates of pneumococcal meningitis in the latter years remained unchanged, with an increasing proportion of cases occurring among children with invasive disease.

© Micah Young / istockphoto.com

The most common 13-valent pneumococcal conjugate vaccine (PCV13) serotypes causing invasive pneumococcal infections in 2011 were 19A and 7F. The declines in invasive infections in 2012 and 2013 were mainly because of declines in serotype 19A and 7F isolates, which decreased by 58% and 54%, respectively, but serotype 3 isolates remained at pre-PCV13 levels, Dr. Sheldon L. Kaplan of Baylor College of Medicine and Texas Children’s Hospital, in Houston, reported at an annual scientific meeting on infectious diseases.

“We had 29 children with invasive pneumococcal disease caused by a PCV13 serotype [in 2012-2013]. All but one were a 19A or serotype 3,” he said at thecombined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Nine children with serotype 19A isolates, and 4 with serotype 3 isolates had received at least two doses of PCV13 prior to developing infections. In 2013, 3 of 12 children with 19A isolates had received four PCV13 doses prior to developing serotype 19A infections.

Only three serotype 1-, 7-, and 19F-related invasive infections occurred during the study period, and no serotype 5–related infections occurred.

In 2012-2013, non-PCV13 serotypes – mainly 33F and 22F – accounted for 71% of isolates, Dr. Kaplan said.

Of note, 45% of children at the eight hospitals that are part of the U.S. Pediatric Multicenter Pneumococcal Surveillance Study Group – which has been conducting pneumococcal surveillance since 1993 – had an underlying condition during 2011-2013, compared with 37% in 2007-2009. The difference was statistically significant, Dr. Kaplan said, noting that malignancies were the most common type of underlying condition, followed by central nervous system disorders, genetic disorder, cardiovascular disorders, and renal disorders.

Non-PCV13 serotypes accounted for 78% of isolates from children with underlying conditions, he said.

Mortality was 0.8% (5 of 626) in 2007-2009, and 3.7% (13 of 352) in 2011-2013. Of the 13 children who died in 2011-2013, 10 had a non-PCV13 serotype, and 9 had an underlying condition, Dr. Kaplan said.

Almost all (99%) of non–central nervous system infections in 2011-2013 were susceptible to penicillin and ceftriaxone.

“Continued surveillance is warranted, especially to monitor non-PCV13 serotypes associated with invasive pneumococcal disease,” he said.

As for pneumococcal meningitis, rates decreased significantly after the introduction of PCV7, but the proportion among children with invasive pneumococcal disease increased by 67% over time, accounting for 12% of cases during 2007-2009, compared with 20% of cases during 2011-2013, according to Dr. Liset Olarte, also of Baylor College of Medicine and Texas Children’s Hospital.

The proportion decreased by 21% among children younger than 24 months, but increased significantly in those aged 24 to 59 months, she noted.

Clinical data showed that in 2007-2009, 19A, 7F, and 3 were the most common serotypes associated with pneumococcal meningitis in the eight hospitals in the surveillance study group. In 2011-13, 19A remained the most common serotype, followed by non-PCV13 serotypes 35B and 22F. Overall, non-PCV13 serotypes causing pneumococcal meningitis increased in both number of cases (24 to 49) and proportion of cases (46% to 73%) after PCV13 introduction.

“In our study, only the change in serotype 7F was statistically significant,” said Dr. Olarte.

The proportion of isolates that were non-susceptible to penicillin did not change significantly from 2007-2009 to 2011-2013 (26% and 25%, respectively), but the proportion nonsusceptible to ceftriaxone, and thus requiring vancomycin for treatment, decreased significantly – by 77% – from 13% to 3%.

All of the isolates with a ceftriaxone minimum inhibitory concentration of 1 mcg/mL or greater and penicillin minimum inhibitory concentration of 2 mcg/mL or greater were serotype 19A, Dr. Olarte said.

Mortality did not change significantly during the study period, but there was a marked, significant increase in hemiparesis cases, from 1% to 12%, after introduction of PCV13. However, this increase was not associated with any particular serotype.

Additionally, subdural empyema on neuroimaging increased from 1% to 16%, but was not associated with any particular serotype and was not associated with the cases of hemiparesis.

Overall, 52% of survivors had some sort of neurologic sequelae at the time of discharge, but there were no differences in terms of specific sequelae between the two groups.

The rates of morbidity and mortality for pneumococcal meningitis remain substantial and have not changed significantly since introduction of PCV13, Dr. Olarte said.

However, if the number of cephalosporin nonsusceptible pneumococci isolated from children with meningitis continues to decrease, modification of empiric antibiotic selection for suspected bacterial meningitis might be considered in the future, therefore ongoing surveillance is warranted, she said.

The studies were partially supported by Pfizer. The authors reported having no other disclosures.