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The Resistance Problem

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

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The Resistance Problem

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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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