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Bacterial resistance to penicillin G by decreased affinity of penicillin-binding proteins: a mathematical model.

Temime L, Boëlle PY, Courvalin P, Guillemot D - Emerging Infect. Dis. (2003)

Bottom Line: Using a mathematical model, we studied determinants of this difference and attempted to anticipate trends in meningococcal resistance to penicillin G.The model predicted that pneumococcal resistance in a population similar to that of France might emerge after 20 years of widespread use of beta-lactam antibiotics; this period may vary from 10 to 30 years.The distribution of resistance levels became bimodal with time, a pattern that has been observed worldwide.

View Article: PubMed Central - PubMed

Affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 444, Paris, France. temime@u444.jussieu.fr

ABSTRACT
Streptococcus pneumoniae and Neisseria meningitidis have very similar mechanisms of resistance to penicillin G. Although penicillin resistance is now common in S. pneumoniae, it is still rare in N. meningitidis. Using a mathematical model, we studied determinants of this difference and attempted to anticipate trends in meningococcal resistance to penicillin G. The model predicted that pneumococcal resistance in a population similar to that of France might emerge after 20 years of widespread use of beta-lactam antibiotics; this period may vary from 10 to 30 years. The distribution of resistance levels became bimodal with time, a pattern that has been observed worldwide. The model suggests that simple differences in the natural history of colonization, interhuman contact, and exposure to beta-lactam antibiotics explain major differences in the epidemiology of resistance of S. pneumoniae and N. meningitidis.

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(a) Time to emergence of the first Streptococcus pneumoniae with a given MIC (full line) and time required for 20% of the bacterial population to reach this MIC (dotted line), starting from an all-susceptible pneumococcal population. Error bars correspond to stochastic variations in the model simulations (10th and 90th percentiles based on 100 simulations). (b) Simulated and (c) observed changes with time since 1987 in the distribution of resistance levels in the pneumococcal population in France. Observed data are taken from the Centre National de Référence des Pneumocoques (4).
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Figure 2: (a) Time to emergence of the first Streptococcus pneumoniae with a given MIC (full line) and time required for 20% of the bacterial population to reach this MIC (dotted line), starting from an all-susceptible pneumococcal population. Error bars correspond to stochastic variations in the model simulations (10th and 90th percentiles based on 100 simulations). (b) Simulated and (c) observed changes with time since 1987 in the distribution of resistance levels in the pneumococcal population in France. Observed data are taken from the Centre National de Référence des Pneumocoques (4).

Mentions: By applying the model to a population in which all the pneumococci were initially susceptible to penicillin G (MIC < 0.06 µg/mL), we determined the time of emergence of the first strains with decreased susceptibility (MIC = 0.125, 0.25, 0.5, and 1 µg/mL), as well as the first resistant strains (MIC = 2 µg/mL) and highly resistant strains (MIC = 4 µg/mL). The model also provided information on the variability of these emergence times (Figure 2a). In particular, the model predicted the emergence of high resistance levels (MIC >2 µg/mL) after approximately 20 years of antibiotic use.


Bacterial resistance to penicillin G by decreased affinity of penicillin-binding proteins: a mathematical model.

Temime L, Boëlle PY, Courvalin P, Guillemot D - Emerging Infect. Dis. (2003)

(a) Time to emergence of the first Streptococcus pneumoniae with a given MIC (full line) and time required for 20% of the bacterial population to reach this MIC (dotted line), starting from an all-susceptible pneumococcal population. Error bars correspond to stochastic variations in the model simulations (10th and 90th percentiles based on 100 simulations). (b) Simulated and (c) observed changes with time since 1987 in the distribution of resistance levels in the pneumococcal population in France. Observed data are taken from the Centre National de Référence des Pneumocoques (4).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2957969&req=5

Figure 2: (a) Time to emergence of the first Streptococcus pneumoniae with a given MIC (full line) and time required for 20% of the bacterial population to reach this MIC (dotted line), starting from an all-susceptible pneumococcal population. Error bars correspond to stochastic variations in the model simulations (10th and 90th percentiles based on 100 simulations). (b) Simulated and (c) observed changes with time since 1987 in the distribution of resistance levels in the pneumococcal population in France. Observed data are taken from the Centre National de Référence des Pneumocoques (4).
Mentions: By applying the model to a population in which all the pneumococci were initially susceptible to penicillin G (MIC < 0.06 µg/mL), we determined the time of emergence of the first strains with decreased susceptibility (MIC = 0.125, 0.25, 0.5, and 1 µg/mL), as well as the first resistant strains (MIC = 2 µg/mL) and highly resistant strains (MIC = 4 µg/mL). The model also provided information on the variability of these emergence times (Figure 2a). In particular, the model predicted the emergence of high resistance levels (MIC >2 µg/mL) after approximately 20 years of antibiotic use.

Bottom Line: Using a mathematical model, we studied determinants of this difference and attempted to anticipate trends in meningococcal resistance to penicillin G.The model predicted that pneumococcal resistance in a population similar to that of France might emerge after 20 years of widespread use of beta-lactam antibiotics; this period may vary from 10 to 30 years.The distribution of resistance levels became bimodal with time, a pattern that has been observed worldwide.

View Article: PubMed Central - PubMed

Affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 444, Paris, France. temime@u444.jussieu.fr

ABSTRACT
Streptococcus pneumoniae and Neisseria meningitidis have very similar mechanisms of resistance to penicillin G. Although penicillin resistance is now common in S. pneumoniae, it is still rare in N. meningitidis. Using a mathematical model, we studied determinants of this difference and attempted to anticipate trends in meningococcal resistance to penicillin G. The model predicted that pneumococcal resistance in a population similar to that of France might emerge after 20 years of widespread use of beta-lactam antibiotics; this period may vary from 10 to 30 years. The distribution of resistance levels became bimodal with time, a pattern that has been observed worldwide. The model suggests that simple differences in the natural history of colonization, interhuman contact, and exposure to beta-lactam antibiotics explain major differences in the epidemiology of resistance of S. pneumoniae and N. meningitidis.

Show MeSH
Related in: MedlinePlus