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. 2016 May 19:6:31234.
doi: 10.3402/iee.v6.31234. eCollection 2016.

Long-term effects of penicillin resistance and fitness cost on pneumococcal transmission dynamics in a developed setting

Affiliations

Long-term effects of penicillin resistance and fitness cost on pneumococcal transmission dynamics in a developed setting

Diana Tilevik. Infect Ecol Epidemiol. .

Abstract

Background: The increasing prevalence of penicillin non-susceptible pneumococci (PNSP) throughout the world threatens successful treatment of infections caused by this important bacterial pathogen. The rate at which PNSP clones spread in the community is thought to mainly be determined by two key determinants; the volume of penicillin use and the magnitude of the fitness cost in the absence of treatment. The aim of the study was to determine the impacts of penicillin consumption and fitness cost on pneumococcal transmission dynamics in a developed country setting.

Methods: An individual-based network model based on real-life demographic data was constructed and applied in a developed country setting (Sweden). A population structure with transmission of carriage taking place within relevant mixing groups, i.e. families, day care groups, school classes, and other close contacts, was considered to properly assess the transmission dynamics for susceptible and PNSP clones. Several scenarios were simulated and model outcomes were statistically analysed.

Results: Model simulations predicted that with an outpatient penicillin use corresponding to the sales in Sweden 2010 (118 recipes per 1,000 inhabitants per year), the magnitude of a fitness cost for resistance must be at least 5% to offset the advantage of penicillin resistance. Moreover, even if there is a fitness cost associated with penicillin resistance, a considerable reduction of penicillin usage appears to be required to significantly decrease the incidence of PNSP in a community.

Conclusion: The frequency of PNSP clones is hard to reverse by simply reducing the penicillin consumption even if there is a biological cost associated with resistance. However, because penicillin usage does promote further spread of PNSP clones, it is important to keep down penicillin consumption considering future resistance problems.

Keywords: Streptococcus pneumoniae; antibiotic resistance; individual-based; infectious disease epidemiology; network model; penicillin non-susceptible pneumococci; pneumococci.

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Figures

Fig. 1
Fig. 1
Simplified graphic illustration of the network model concept. The blue boxes represent households, the green box represents day care centre, whereas the yellow box represents school. Individuals within the same household have contact with each other, whereas individuals within the same day care centre or school have contact with each other only if they belong to the same group or class, respectively. Disease transmission can only occur via edges, i.e., contacts between vertices, i.e., individuals. The edges are bidirectional, that is, disease may be transmitted in both directions. Adapted from Karlsson et al. (20).
Fig. 2
Fig. 2
Model flowchart. The age-structured population and the contact structure were held constant between and during simulations. All simulations were initiated with equivalent sets of pneumococcal carriers, and all parameters, except for volume of outpatient penicillin consumption and transmission probabilities reflecting fitness costs, were held constant for each scenario. PSP=penicillin-susceptible pneumococci.
Fig. 3
Fig. 3
Outcomes for scenarios simulated using varying fitness cost for the PNSP clone. For each scenario, 100 simulations were performed and the outcomes were averaged to find the most probable outcome. The implemented fitness costs for the PNSP clone ranged between 0 and 10%. (a) Relative frequency of average number of transmissions for the penicillin-susceptible pneumococci clone and the PNSP clone. (b) Plot of average number of transmissions for the PNSP clone against fitness cost with fitted regression line (F1,9=311, p<0.001; average number of transmissions=17,843 – 1,326×fitness cost (%), r2=0.97). Error bars indicate 95% confidence interval. PNSP, penicillin non-susceptible pneumococci.
Fig. 4
Fig. 4
Average number of transmissions for susceptible clone and PNSP clone by implementing reduced outpatient penicillin consumption. The fitness cost for the PNSP clone was fixed at 5% and the default penicillin consumption was set according Sweden year 2010 (44). Error bars indicate 95% confidence interval. PNSP, penicillin non-susceptible pneumococci.
Fig. 5
Fig. 5
Average number of transmissions for susceptible clone and PNSP clone by implementing varying degrees of penicillin consumption. (a) 5% fitness cost for the PNSP relative to the susceptible clone. One-way ANOVA ( F2,297=27.9, p<0.001) followed by post hoc Tukey test revealed significant differences in the number of transmissions for the PNSP clone between low and no penicillin consumption (p<0.001) as well as between high and no penicillin consumption (p<0.001). (b) 10% fitness cost for the PNSP relative to the susceptible clone. One-way ANOVA (F2,297=14.4, p<0.001) followed by post hoc Tukey test revealed significant differences in the number of transmissions for the PNSP clone between low and no penicillin consumption (p<0.001), as well as between high and no penicillin consumption (p<0.001). Error bars indicate 95% confidence interval. PNSP, penicillin non-susceptible pneumococci.

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