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author:("hemimer, L.")
2.  Short- and Long-Term Effects of Pneumococcal Conjugate Vaccination of Children on Penicillin Resistance 
Recent observations have shown that wide-scale vaccination with pneumococcal conjugate vaccines was associated with a reduction in invasive disease, supporting the expectation that vaccination could help reduce carriage of Streptococcus pneumoniae and control the spread of resistant strains. However, it is too early to assess whether these effects can be sustained in the long term. Here, we used mathematical modeling to investigate time changes in pneumococcal colonization and resistance induced by conjugate vaccination in an environment where antibiotic exposure is high and resistance is widespread. According to model predictions, vaccination induced a decrease in carriage of vaccine-type pneumococci to very low levels, typically in 10 to 15 years under epidemiologically realistic conditions. Almost simultaneously, non-vaccine-type pneumococci spread in the community. Consequently, while there was a short-term decrease in the overall carriage rate, it was followed after a few years by a renewed, although limited, increase. Vaccination with a heptavalent vaccine did not affect the extent to which antibiotic resistance was selected: in all cases, the distribution of resistance levels peaked at high levels (MIC > 2 μg/ml) after 20 years. With a vaccine optimally designed to include all serotypes currently exhibiting decreased susceptibility to penicillin G, the selection of resistance was slowed down, although not prevented. These results suggest that because of serotype replacement, the effects of vaccination observed today may not be sustained in the long term. As a consequence, vaccination alone may not be successful in controlling selection for resistance in S. pneumoniae.
PMCID: PMC415598  PMID: 15155223
3.  Bacterial Resistance to Penicillin G by Decreased Affinity of Penicillin-Binding Proteins: A Mathematical Model 
Emerging Infectious Diseases  2003;9(4):411-417.
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 β-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 β-lactam antibiotics explain major differences in the epidemiology of resistance of S. pneumoniae and N. meningitidis.
PMCID: PMC2957969  PMID: 12702219
antibiotic resistance, mathematical models, Streptococcus pneumonia, Neisseria meningitidis; penicillin G, microbiology, epidemiology, selection, transmission, perspective

Results 1-3 (3)