,The Resistance Problem,PRSP = Penicillin Resistant Strep. pneumoniae QRSP = Quinolone Resistant Strep. pneumoniae MRSA = Methicillin Resistant Staph. aureus VRE = Vancomycin Resistant EnterococciVRE in Canada: 1993: first isolated 1997: 800 cases MRSA in Ontario: 1992: 9000 casesResistance rates differ dramatically between Canada and the U.S.,The Problem,Graph of Global Resistance patterns?,Principles of Antibiotic Prescribing,Antimicrobial Resistance,Understanding Resistance: Darwins 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),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,Contributing Factors to Resistance,Overuse in humansMore than 50% of antibiotics in Canada are prescribed for viral URTIs 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,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,S. pneumoniae,Spectrum of DiseaseOtitis MediaSinusitisBronchitisPneumoniaMeningitisTreatment Penicillin Cephalosporins Macrolides TMP/SMX Tetracyclines Quinolones,PRSP - Prevalence,1980s - 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),PRSP Cause / Spread,Penicillin exposure selects resistance with S. pneumoniaeWidespread use of antibiotics selects for resistant strains, allowing them to proliferate and spread genes to other bacteria,Message #1,Penicillin exposure selects resistance with S. pneumoniae 2) Penicillin resistance is associated with multi-drug resistance,Message #2,Quinolone Resistant S.pneumoniae,Quinolone Resistant S.pneumoniae,Figure 6. Fluoroquinolone-Resistant Pneumococci: Canadian Bacterial Surveillance Network, 1997-2007,Canadian Bacterial Surveillance Network, March 2008,% Resistant,Figure 7. Fluoroquinolone-Resistant Pneumococci in Respiratory Isolates from Adults 64 years: 1988-2007,Canadian Bacterial Surveillance Network, March 2008,Recommendations: quinolones be reserved for treatment failure or known resistance standard -lactam treatment is effective in sensitive and intermediate resistant pneumococciArch Intern Med. 2000; 160: 1399-1408.,PRSP - Significance,Penicillin exposure selects resistance with S. pneumoniae Penicillin resistance is associated with multi-drug resistance 3) Resistance is relative and can be overcomewith 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.,Message #3,Finland:,N Engl J Med, August 1997,Resistance What can be done?,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,Penicillin: Resistance Rates and Prescriptions (Canadian Bacterial Surveillance Network. 1988, 1993-2005),Canadian Bacterial Surveillance Network, Feb. 2006,Erythromycin: Resistance Rates and Prescriptions (Canadian Bacterial Surveillance Network. 1988, 1993-2005),Canadian Bacterial Surveillance Network, Feb. 2006,