Some types of universal pneumococcal vaccines could increase antibiotic resistance among the bacteria they are intended to suppress, researchers say.
The effect on antibiotic resistance of these new whole-cell or protein-based pneumococcal vaccines, now in clinical trials, depends on such factors as the way drug-resistant and drug-sensitive pneumococcal strains compete with each other, said Katherine Atkins, PhD, an associate professor of infectious disease modeling at the London School of Hygiene and Tropical Medicine, London, United Kingdom.
“At the moment, we’re not entirely sure what the impact will be on antibiotic resistance,” she told Medscape Medical News.
The study by Atkins and colleagues was published online August 11 in Science Translational Medicine.
The use of pneumococcal conjugate vaccines led to a reduction in the incidence of diseases caused by Streptococcus pneumoniae, such as pneumonia, meningitis, and especially otitis media in young children. This decreased the demand for antibiotics to treat these illnesses.
But the conjugate vaccines target only a few of the many pneumococcal serotypes. Suppressing these has opened up niches for other serotypes and has led to a rebound in resistant bacteria.
“While you’re having total reduction in all infections, you do see this rise in resistant infections,” said Atkins.
This in turn has inspired the development of whole-cell and protein-based vaccines that are designed to work against all serotypes. Some of these have shown promise in clinical trials.
Atkins and her colleagues wanted to know how these new vaccines would affect antibiotic resistance. They created mathematical models in which they used data from 2007 on penicillin consumption and penicillin resistance in S pneumoniae invasive isolates from 27 European countries.
They identified four mechanisms by which the balance of resistant and sensitive strains of bacteria could play out. The first two fall into the general category of diversity, and the second two fall into the general category of competition.
First, the antibiotic-sensitive strains might exist in different populations of people — by geographical regions, socioeconomic strata, host age, risk classes, or some combination. If antibiotic use creates resistant strains in one population, the antibiotic-sensitive strains might still exist in another population and reemerge.
Second, equilibrium could persist if the bacteria naturally survive for different durations in the people they infect. Only infections caused by those that last the longest would be treated with antibiotics, allowing the others to survive without developing resistance.
The other two possible mechanisms involve competition. In the first, the balance of sensitive and resistant bacteria might be determined by how much antibiotic is present in their environment.
In the second competition mechanism, evolving resistance to antibiotics may cause bacteria to lose some capacity for growth. With the use of antibiotics, the resistant strains proliferate. But when antibiotics aren’t being used, the antibiotic-sensitive bacteria proliferate even faster.
The four mechanisms are not mutually exclusive. The real-world picture might involve some combination.
The effect of a universal vaccine could depend on whether it works by preventing infection or by speeding the time it takes for people to clear the bacteria once they are infected. Whole-cell vaccines speed clearance, but it’s not clear which way protein-based vaccines work, the researchers write.
A vaccine that works by preventing infection would not affect antibiotic resistance if one of the two diversity mechanisms apply.
But if competition determines the balance among bacteria, a vaccine that works by accelerating clearance could either reduce or increase antibiotic resistance.
Overall, vaccines that accelerate clearance are more likely to reduce resistance — if they are sufficiently efficacious — because the bacteria would have less time to be exposed to antibiotics. If resistance to bacteria has been the key factor in determining competitive advantage, then the sensitive strains would become more common because they would not be competing with resistant strains.
But if sensitive bacteria grow faster than resistant ones, then the resistant strains could gain an advantage because they would no longer be competing with sensitive bacteria.
Policymakers should look closely at what happens as new vaccines are administered to see how resistance is being affected, particularly if there are populations who are not getting vaccinated, Atkins said. “It’s actually a really complicated situation, and one that needs quantifying and not broad brushstroke policy recommendations.”
She and her colleagues are now testing their models by collecting data as a new pneumococcal conjugate vaccine is introduced in Vietnam.
Joanne Yoong, PhD, a senior economist who has studied vaccination and antibiotic resistance at the University of Southern California, in Los Angeles, California, said the modeling “provides a very rigorous, quantitative articulation of the links between vaccines and antimicrobial resistance.” Yoong was not involved in the study.
“For me, I think the policy implication is that our understanding of needs assessment has to be much more comprehensive to have a clear view on these bigger issues for antimicrobial resistance,” she told Medscape Medical News.
Atkins and Yoong have disclosed no relevant financial relationships. The authors of the study were funded by the National Institute for Health Research Health Protection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England.
Sci Transl Med. Published online August 11, 2021. Abstract
Laird Harrison writes about science, health, and culture. His work has appeared in magazines, newspapers, and online publications. He is at work on a novel about alternate realities in physics. Harrison teaches writing at the Writers Grotto. Visit him at lairdharrison.com or follow him on Twitter: @LairdH.
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