What do case-control studies tell us about risk factors for antibiotic resistance?
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Transcript of What do case-control studies tell us about risk factors for antibiotic resistance?
What do case-control studies tell us about risk factors for antibiotic resistance?
Christie Y. JeonEPI502Jan 22nd, 2008
Outline Motivation Randomized Controlled Trial Understanding the outcomes ORS, ORC
Variation of effect Confounding Multiplicative vs. Absolute
Motivation To identify the risk factors for
infection with resistant pathogen Antibiotic use for a given infection A AR , B AR
Who, where, what ? Why?
Interventions Restrictions
Randomized Controlled Trial
PRS = P[R]TX > 1
P[R]NoTx
PRC = P[R I C]TX > 1P[R I C]NoTx PRS < PRC
Case-control studiesA B
Case Colonized with resistant
Colonized with resistant
Controls Colonized with susceptible
Colonized with susceptible OR not colonized
Measure of Association
ORConditional ORSimple
Example
Interpretation of OR
Example – Harris et al. CID 2002
A B
Case Culture positive for imipenem-resistant P. aeruginosa
Controls Culture positive for imipenem-susceptible P. aeruginosa
Randomly selected control patients from same medical services
Interpretation of OR
The increase in an individual’s risk of carrying impR P. aeruginosa due to AB given an infection with susceptible P. aeruginosa(?)
The increase in an individual’s risk of carrying impR P. aeruginosa due to the particular AB
Prediction : Given that an individual has recently been treated with a particular AB, the increased likelihood that the pathogen is impR compared to not having been treated
Example – Harris et al. CID 2002
A B
Case Culture positive for imipenem-resistant P. aeruginosa
Controls Culture positive for imipenem-susceptible P. aeruginosa
Randomly selected control patients from same medical services
Interpretation of OR
The increase in an individual’s risk of carrying impR P. aeruginosa due to AB given an infection with susceptible P. aeruginosa(?)
The increase in an individual’s risk of carrying impR P. aeruginosa due to the particular AB
Community effect : indirect effect of AB on the population as a whole by reducing the overall exposure to susceptible P. aeruginosa
Appropriate case-control design Q : “What are the risk factors for
emergence of AB-resistance in pathogen X among patients previously infected with AB-susceptible pathogen X”
A : Cases : individuals with resistant organism
who previously had the susceptible form of the organism
Controls : individuals with the susceptible pathogen and no subsequent resistant organism
Example – Harris et al. CID 2002
B AR
PRc B < PRc A
PRc B= P[R I C]TX > 1
P[R I C]NoTx
Tx clears some R-pathogen
PRS= P[R]TX < 1
P[R]NoTx
PRC = P[R I C]TX >1P[R I C]NoTx PRS < PRC
Outbreak
PRS = P[R]TX > 1
P[R]NoTx
PRC = P[R I C]TX >> 1P[R I C]NoTx PRS < PRC
Confounding Time at risk of resistant pathogen Duration at risk of resistant
pathogen Comorbid illness Location of recruitment
Multiplicative vs. Absolute Odds, Rate, Risk Ratio =
multiplicative measure Prediction Causal association
Rate Difference = absolute measure Burden of disease Population effect
Schwaber et al. 2004
A B
C
DE
Recovering rates from case-control studies
RateTX = # casesTX controlsTX x 3
RateNoTx = # casesNo Tx controlsNo Tx x 3
Summary Strength and meaning of the association
of antibiotic use and resistance varies by Definition of the controls Effect on the susceptible strains The nature of the antibiotic Background incidence of resistance strains
Absolute measures are better measure of burden of resistance in the population