What can we learn from individual- level studies of antibiotic resistance? Molly Franke EPI 502 January 17, 2008

Outline Overview: individual-level studies Utility of individual-level studies Answerable questions Potential pitfalls / challenges Methicillin Resistant Staphylococcus Aureus

Individual Level Studies Cohort studies Case-control studies Cross-sectional studies  Time JanDec  Time JanDec

Utility of individual-level studies Directly link exposure and outcome Improved confounding control Step closer to causation (v. association) Individual effects 

Answerable Questions 1.Are there individual effects of antibiotic use on resistance? 2.Does individual effect of antibiotics differ by other variables? 3.Who is at highest risk for resistance? 4.When might interventions perform differently under different circumstances?

1. Individual effects Samore et al (Am J Epidemiol, 2006)

But… confounding? Analysis controlled for age, hh size, community, and year Unmeasured confounding? U CephalosporinCarriageCephalosporin

1. Individual effects Leibovici et al, J Antimicrob Chem 2001

2. Effects may differ by antibiotic Different antibiotic mechanisms Example: Strep pneumo carriage Cephalosporin, but not penicillin use associated with resistant carriage CephalosporinPenicillin Samore et al (Am J Epidemiol, 2006)

3. High risk groups Who should we target for interventions? Examples: Enteral feeding tubes VRE carriage Nonadherence increases TB resistance Interventions Altering feeding tube strategies DOT

4. Effect modification Interventions may work differently under different circumstances. Intervention modified by potential for transmission Example: VRE carriage (Bonten, Arch Intern Med 1998) At low colonization pressure, enteral tubes, antibiotic pressure predicted carriage When colonization pressure >50%, other variables had very little effect Bonten Arch Intern Med 1998

Another estimable quantity Samore, Am J Epidemiol, 2006 Exposure window

Potential pitfalls Independence assumptions –Example: Cox model Consider causal structure Colonization pressure: % of carriers in a pop. Hand washing Colonization pressure Carriage

Limitations Cost / Time Generalizeability Individual effect may vary by resistance levels Only half the story

Conclusions What can we learn from individual-level studies? INDIVIDUAL EFFECTS Expanded insight with: Multi-level models Mathematical modeling

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