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Macrolide Resistance Genotypes
Genotype Year
2001-2 2002-3 2003-4 2004-5 2005-6 2006-7 2007-8 p-value
(n=55) (n=41) (n =42) (n=57) (n=84) (n=93) (=89)
mefA+ermB- 72.7% 70.7% 52.4% 50.9% 40.5% 44.1% 34.8% <.0001
mefA-ermB+ 20.0% 26.8% 26.2% 36.8% 40.5% 31.2% 46.1% .01
ermB+mefA 1.8% 0.0% 9.5% 10.5% 17.9% 23.7% 19.1% <.0001
+
23S rRNA 3.6% 2.4% 7.1% 0.0% 1.2% 1.1% 1.1% .17
(A2059G)](https://image.slidesharecdn.com/dynamicepidemiologyofstreptococcuspneumoniae-joshuametlaymdphd-111202144428-phpapp01/75/Dynamic-Epidemiology-of-Streptococcus-pneumoniae-Joshua-Metlay-MD-PhD-21-2048.jpg)
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Dynamic Epidemiology of Streptococcus pneumoniae- Joshua Metlay MD PhD
This document summarizes trends in Streptococcus pneumoniae (pneumococcus) epidemiology based on a presentation given by Dr. Joshua Metlay. It discusses: 1) Secular trends including increasing antimicrobial resistance and serotype replacement over time. 2) Geographic patterns that show higher risks of pneumococcal disease in certain neighborhoods which may be influenced by host, pathogen, and vector factors. 3) The impact of pneumococcal conjugate vaccines in reducing rates of invasive pneumococcal disease, particularly among children, but also indirectly in adults through herd immunity effects. Emerging non-vaccine serotypes now cause a larger proportion of disease.
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Dynamic Epidemiology of Streptococcus pneumoniae- Joshua Metlay MD PhD
- 1. The Dynamic Epidemiologyof Streptococcus pneumoniae. Joshua P. Metlay, MD, PhD Division of General Internal Medicine University of Pennsylvania Presented at the 41st Annual Symposium “Global Movement of Infectious Pathogens and Improved Laboratory Detection” Eastern PA Branch-American Society for Microbiology November 17, 2011 Thomas Jefferson University, Philadelphia
- 2. Outline • Introduction topneumococcal disease • Secular trends –Antimicrobial drug resistance (macrolides) –Serotype replacement • Geographic patterns
- 4. Survival from pneumococcalbacteremia 1952-1962
- 5. Penicillin Resistance inS. pneumoniae United States 1979-2000 Sentinel ABCs 1979-1994: CDC Sentinel Surveillance Network 1995-2002: CDC Active Bacterial Core Surveillance (ABCs) /Emerging Infections Program
- 7. The Delaware ValleyHospital Network • Hospital based reporting of cases of pneumococcal bacteremia • Established in 2001 • Centralized susceptibility testing • 48 hospitals in the 5 county region of Southeastern Pennsylvania • 3.7 million population • 400 annual cases
- 8. Participating hospitals inthe Delaware Valley Emerging Infectious Diseases 2001
- 9. Risk Factors forPneumococcal Bacteremia Characteristic Cases per 100,000 95% CI Age 18-49 8.3 7.5 – 9.2 50-64 15.9 14.4 – 17.6 65-79 26.4 26.4 – 29.5 80+ 59.4 52.7 – 67 Race White 13.7 12.9 – 14.7 African American 26.4 24.2 – 28.9
- 10.
- 11. Pneumococcal Conjugate Vaccine •Seven valent conjugate vaccine licensed in February 2000 • 4, 6B, 9V, 14, 18C, 19F, 23F • Widespread use by June 2000. • 2,4, 6, 13-15 month immunization schedule • Efficacy for otitis media, invasive disease, pneumonia. • Reduction in carriage of vaccine serotypes
- 12. Temporal trends inrisk of invasive pneumococcal disease: children
- 13. Temporal trends inrisk of invasive pneumococcal disease: adults
- 14. What is HerdImmunity? Picture courtesy of Dr. C. Whitney
- 15. Early Successes withVaccination Rate of VT IPD per 100,000 population Direct effect: 94% decrease Indirect effect: 65% decrease CDC. MMWR 2005; 54: 893-7.
- 16. Vaccination of childrenreduces risk of disease in adults 100 Cases Controls 80 60 % 40 20 0 Any child vaccinated Youngest child vaccinated Vaccine. 2006
- 17. Archives of IM2010
- 18. CLSI Breakpoints 2011 Drug MIC (ug/mL) Interpretive Standard S I R Penicillin (Meningitis) ≤ 0.06 0.12-1 ≥2 Penicillin (Non-meningitis) ≤2 4 ≥8 Erythromycin ≤0.25 0.5 ≥1
- 21. [1] Macrolide Resistance Genotypes Genotype Year 2001-2 2002-3 2003-4 2004-5 2005-6 2006-7 2007-8 p-value (n=55) (n=41) (n =42) (n=57) (n=84) (n=93) (=89) mefA+ermB- 72.7% 70.7% 52.4% 50.9% 40.5% 44.1% 34.8% <.0001 mefA-ermB+ 20.0% 26.8% 26.2% 36.8% 40.5% 31.2% 46.1% .01 ermB+mefA 1.8% 0.0% 9.5% 10.5% 17.9% 23.7% 19.1% <.0001 + 23S rRNA 3.6% 2.4% 7.1% 0.0% 1.2% 1.1% 1.1% .17 (A2059G)
- 22.
- 24. PCV-13 • Introduction ofPCV-13 in 2000 • Coverage of PCV-7 serotypes: –4,6B,9V,14,18C,19F,23F • Additional serotypes: –1,3,5,6A,7F,19A
- 25. Pediatric Carriage ofPneumococcal Serotypes 2008-2010 20 18 16 6C 14 35B 19A % of isolates 12 11A 15C 10 23B 23A 8 15A 21 6 15B like 16F 4 22F 15B 2 0 2008 2009 2010 YEAR
- 26.
- 27. Tobler’s First Lawof Geography “Everything is related to everything else, but near things are more related than distant things’’
- 28.
- 29. Disease risk variesby neighborhood
- 30.
- 31. Why are thereclusters of disease? • Small area outbreaks from highly virulent clones – Pathogen Hypothesis • Neighborhood level exposures influence risk of transmission – Vector Hypothesis • Heterogenous population distribution – Host Hypothesis
- 34. PFGE Analysis ofPneumo Isolates
- 35. Genetic clustering vs.geographic clustering
- 37. Children as Vectors Huang CID 2005
- 40. Child Exposure isAssociated with Reduced Risk of Disease Characteristic Cases per 100,000 95% CI # of children in home 0 21.5 20.3 – 22.8 1 8.3 6.8 – 9.9 2+ 3.3 2.6 – 4.2 Archives of Internal Med 2010
- 41. Key Points • Overallrisk of pneumococcal disease has declined but new serotypes are emerging • Emerging serotypes are primarily multidrug resistance, reflecting selection of MDR clones and expansion of previously low prevalence serotypes • Variation in disease risk likely reflects host factors, but vector and pathogen factors are rapidly changing in pneumococcal disease.
- 42. Thanks • Robert Austrian • Marshall Joffe • Lou Bell • Ebb Lautenbach • Catherine Berjohn • Yimei Li • Charlie Branas • Zhenying Liu • Linda Crossette • Russell Localio • Chris Czaja • Mat Macdonald • Paul Edelstein • Irv Nachamkin • Kristen Feemster • Samir Shah • Neil Fishman • Justine Shults • James Flory • Tony Smith