Antibiotic Resistance Rises After PCV13 Vaccine Introduced to Fight Pneumococcal Disease

Antibiotic-resistant Streptococcus pneumoniae strains are on the rise since the introduction of the 13-valent pneumococcal conjugate vaccine in 2010, a new study suggests.

The study, published in Clinical Infectious Diseases, examined antibiotic susceptibility of 1201 isolates of S pneumoniae collected from 448 children aged 6 to 36 months in primary care settings in Rochester, New York, from 2006-16.

The study found that, beginning in 2013, Streptococcus pneumoniae isolates began to show less susceptibility to penicillin, third-generation cephalosporins, fluoroquinolones and carbapenems, as new strains emerged in prevalence.

“Our study shows that an increase in pneumococcal carriage in the nose of children and ear infections caused by pneumococci began to occur about 3 years after introduction of PCV13, in 2013,” Michael E. Pichichero, MD, of Rochester General Hospital Research Institute told Contagion^®. “Three strains especially increased (serotypes 35B, 35F and 11A). These dominant emerging strains have a competitive advantage due to multiple antibiotic resistance.”

Use of antibiotics contributes to the increase in 35B, 35F and 11A strains that are resistant to those antibiotics commonly used to treat sepsis of unknown cause. Those strains also saw an increase in resistance to those drugs.

“Physicians rely on the supposition that these drugs will kill all pneumococci,” Pichichero told Contagion^®. “However, our study suggests that these incredibly valuable broad-spectrum antibiotics may soon lose their effectiveness against serotype 35B, 35F and/or 11A strains. Unfortunately, neither PCV15 (Merck) or PCV20 (Pfizer) include a serotype 35B or 35F strains as an ingredient, PCV20 will include serotype 11A.”

The study noted that the rise in prevalence of these antibiotic-resistant strains is similar to that seen with serotype 19A after the introduction of the PCV7 vaccine in 2000. Serotype 19A — which emerged in place of strains eliminated by PCV7 and grew to account for about 50% of pneumococcal infections in 2010 — was virtually eliminated after PCV13 was introduced. Since then, the new antibiotic-resistant strains (serotypes 35B, 35F and 11A) have emerged in place of serotype 19A.

“History repeats itself,” Pichichero told Contagion^®. “Antibiotic resistance among Streptococcus pneumoniae strains isolated from children is rising since 2013 due to serotypes not included in the13-valent pneumococcal conjugate vaccine (PCV13) and the strains have a different profile of antibiotic susceptibility (decreasing susceptibility to penicillins, third-generation cephalosporins, fluoroquinolones and carbapenems) compared to the pre-PCV13 era.”

Vaccinating children against pneumococci has been shown to produce a secondary herd immunity in adults, as bacteria commonly spread from children to adults. This study yielded some surprises.

“We were very surprised by the specific findings but not the general phenomena of pneumococcal strain replacement and increases in prevalence of antibiotic-resistant strains,” Pichichero told Contagion^®. “The pattern of antibiotic resistance to include fluoroquinolones suggests that kids acquire pneumococci from adults since kids infrequently are treated with those antibiotics. So, contagion goes both ways: kids to adults and adults to kids.”

More research is needed to examine possible variations in pneumococcal strain emergence due to geographic or demographic differences.

As vaccination has contributed to the changing epidemiology of pneumococcal disease, health officials have weighed new strategies, such as discussing vaccination with more older patients and encouraging development of a new vaccine to prevent pneumococcal meningitis, which has been rising due to strains not included in the vaccine, according to a recent study.

The US Centers for Disease Control and Prevention listed drug-resistant Streptococcus pneumoniae in a 2019 report of bacteria and fungi that are a serious antibiotic resistance threat, with an estimated 900,000 infections and 3,600 deaths in 2014.