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