Carriage burden, multiple colonization and antibiotic pressure promote emergence of resistant vaccine escape pneumococci

Abstract

Pneumococcal conjugate vaccines target the limited subset of the more than 90 known serotypes of Streptococcus pneumoniae responsible for the greatest burden of pneumococcal disease and antibiotic resistance. Following the introduction of these vaccines, serotypes not targeted were able to expand and resistance became more common within these types. Here we use a stochastic dynamic model of pediatric pneumococcal carriage to evaluate potential influences on the emergence of new resistant lineages following the introduction of a vaccine targeting more common resistant types. Antibiotic pressure was the strongest driver, with no emergence at low levels and universal emergence at high levels. At intermediate levels of antibiotic pressure, higher carriage burden and a greater degree of dual carriage promoted emergence. This may have implications for current plans to introduce childhood pneumococcal vaccination in several high-burden countries.

Keywords: Streptococcus pneumoniae; emergence; model; resistance; vaccination.

Figure 1.

Box diagram of model. Each compartment is further subdivided into vaccinated and unvaccinated populations. The U compartment is uncolonized and subscripts in each colonized (I) compartment indicate the colonizing strains (V, VT-R; N, NVT-S; R, NVT-R). In the vaccinated population, λ_V is replaced by vλ_V. Entry occurs into the U compartment and exit out of the model population occurs at the same rate from all compartments (not shown). All I compartments recover into the U compartment at rate d.

Figure 2.

Proportion of realizations in which emergence (final NVT-R strain prevalence more than 10%) was observed by degree of antibiotic pressure. Each point represents a combination of antibiotic pressure (x-axis), carriage burden (lines) and relative acquisition rate k of dual versus single carriage (panels).

Figure 3.

Effect of dual carriage on the final prevalence of the NVT-R strain. Each point represents the mean final prevalence of the NVT-R strain at a particular combination of dual carriage relative acquisition rate k (x-axis), carriage burden (lines) and antibiotic pressure (panels).