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Understanding and Combatting Antibiotic Resistance: The Case of Pneumococci in Canada

Antibiotic resistance is a growing concern in Canada, especially with pathogens such as Penicillin-Resistant Streptococcus pneumoniae (PRSP) and Quinolone-Resistant Streptococcus pneumoniae (QRSP). This paper discusses the rise in MRSA and VRE cases and highlights alarming trends in antibiotic over-prescription, particularly for viral infections. It explores the implications for patient care, including treatment failures and increased healthcare costs. The need for responsible antibiotic prescribing practices and robust surveillance is emphasized to combat these resistant strains effectively.

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Understanding and Combatting Antibiotic Resistance: The Case of Pneumococci in Canada

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  1. The Resistance Problem • PRSP = Penicillin Resistant Strep. pneumoniae • QRSP = Quinolone Resistant Strep. pneumoniae • MRSA = Methicillin Resistant Staph. aureus • VRE = Vancomycin Resistant Enterococci • VRE in Canada: 1993: first isolated 1997: >800 cases • MRSA in Ontario: 1992: <100 cases  2000: >9000 cases • Resistance rates differ dramatically between Canada and the U.S.

  2. The Problem • Graph of Global Resistance patterns?

  3. Principles of Antibiotic Prescribing

  4. Antimicrobial Resistance • Understanding Resistance: • Darwin’s theory of natural selection • Minimum Inhibitory Concentration (MIC) • Clinical and Laboratory Standards Institute (CLSI) reporting system based on MIC: Susceptible (S) Intermediate (I) Resistant (R)

  5. Interpretation of Susceptibility Data: • In vitro susceptibility testing only involves the bug and the drug • Antimicrobial resistance vs clinical resistance • MIC value needs to be considered in context of patient factors • Type of infection • Location of infection • Antibiotic distribution • Antibiotic concentration at site of infection

  6. Contributing Factors to Resistance • Overuse in humans More than 50% of antibiotics in Canada are prescribed for viral URTI’s • Animal and agricultural use: • Accounts for 50% of all antimicrobials • Used for prevention/treatment of infection and growth promotion • Evidence of resistant strains in livestock

  7. Implications Of Resistance • Treatment failure • Forced to use more toxic alternatives • Possibility of no alternate agents (e.g., vancomycin-resistant S. aureus) • Longer hospital stays • Forced to use more expensive alternatives and other increased healthcare costs

  8. S. pneumoniae • Spectrum of Disease • Otitis Media • Sinusitis • Bronchitis • Pneumonia • Meningitis • Treatment • Penicillin • Cephalosporins • Macrolides • TMP/SMX • Tetracyclines • Quinolones

  9. PRSP - Prevalence 1980s - < 2.0% 1998 - 16.0% (with up to 5% with high-level resistance) 1999 - 12.0% 2000 - 12.3 – 16.9% CMAJ 2002; 167(8)

  10. Figure 1. Percentage of Penicillin Non-Susceptible S. pneumoniae in Canada: 1988-2007 Canadian Bacterial Surveillance Network, March 2008

  11. Penicillin Resistant S. pneumoniae Isolates Ontario 1988, 1993-2005 Canadian Bacterial Surveillance Network, March 2006

  12. Figure 5. Macrolide-Resistant Pneumococci: Canadian Bacterial Surveillance Network, 1988-2007 Canadian Bacterial Surveillance Network, March 2008

  13. Figure 4. Percentage of Non-susceptible Isolates ofS. pneumoniae in Geographic Regions of Canada, 2007 Canadian Bacterial Surveillance Network, March 2008

  14. PRSP – Cause / Spread JAMA 1998;279:365-370. • 941 children in observational study • Nasopharyngeal carriage of S. pneumoniae determined • Low doses and long duration of ß-lactam treatment was associated with increasing penicillin resistance

  15. PRSP – Cause / Spread BMJ 2002; 324 - 461 children in Australia • Examined nasopharyngeal carriage of S. pneumoniae • Likelihood of carrying PRSP doubled in children who had used a beta-lactam in the previous 2 months • >7 days of antibiotics resulted in higher PRSP carriage • PRSP present even in children who had not taken antibiotics for 6 months (likely acquired through transmission from others)

  16. Message #1 • Penicillin exposure selects resistance with S. pneumoniae Widespread use of antibiotics selects for resistant strains, allowing them to proliferate and spread genes to other bacteria

  17. Message #2 • Penicillin exposure selects resistance with S. pneumoniae 2) Penicillin resistance is associated with multi-drug resistance

  18. Quinolone Resistant S.pneumoniae

  19. Quinolone Resistant S.pneumoniae

  20. Figure 6. Fluoroquinolone-Resistant Pneumococci:Canadian Bacterial Surveillance Network, 1997-2007 % Resistant Canadian Bacterial Surveillance Network, March 2008

  21. Figure 7. Fluoroquinolone-Resistant Pneumococci in Respiratory Isolates from Adults >64 years: 1988-2007 Canadian Bacterial Surveillance Network, March 2008

  22. PRSP - Significance • Recommendations: • quinolones be reserved for treatment failure or known resistance • standard -lactam treatment is effective in sensitive and intermediate resistant pneumococci Arch Intern Med. 2000; 160: 1399-1408.

  23. Message #3 • Penicillin exposure selects resistance with S. pneumoniae • Penicillin resistance is associated with multi-drug resistance 3) Resistance is relative and can be overcome with increasing doses of penicillins, if tolerated. However, S. pneumoniae resistance to macrolides and TMP-SMX is high level and cannot be overcome by increasing dosages.

  24. Resistance – What can be done? • Finland: N Engl J Med, August 1997

  25. Anti-infective Guidelines • Independent physician panel • Arms length from government, industry • Focus on optimal patient care • Best available evidence, including Canadian references • Published 1994, 1997, 2001, 2005

  26. Penicillin: Resistance Rates and Prescriptions(Canadian Bacterial Surveillance Network. 1988, 1993-2005) Canadian Bacterial Surveillance Network, Feb. 2006

  27. Erythromycin: Resistance Rates and Prescriptions(Canadian Bacterial Surveillance Network. 1988, 1993-2005) Canadian Bacterial Surveillance Network, Feb. 2006

  28. Take Home Messages Antibiotics are good drugs, when used properly • Always consider if infection is Bacterial vs Viral • Try to use NO antibiotic or 1st line antibiotics first • Narrow vs broad spectrum antibiotics • Care about the consequences of prescribing antibiotics (resistance, side effect, C.difficile, cost) • Provide professional/community leadership • Partner with and educate/support your patients

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