The Case-Case-Control Study Design: Addressing the Limitations of Risk Factor Studies for Antimicrobial Resistance

Abstract

The case-case-control study design is an effective method for identifying risk factors for antimicrobial-resistant pathogens. Although the case-case-control study design has limitations, it is, in our opinion, more informative and less flawed than the standard case-control study design.

Determination of Risk Factors Associated With Isolation of Linezolid-Resistant Strains of Vancomycin-Resistant Enterococcus

“…For case patients, time at risk was considered the period prior to isolation Enterococcus in clinical culture, and for control patients, it was the complete length of hospital stay. 18 This is not a surprising finding as increased length of stay is a well-known risk factor for isolation of resistant organisms, and it further emphasizes the importance of horizontal transmission as an explanation for the isolation of linezolid-resistant VRE.…”

“…This methodology ensures that the importance of previous antibiotic exposure will not be overestimated (as is seen in a case-control study in which uninfected patients serve as the control group) and that the importance of horizontal transmission will not be lost (as is seen in a case-control study in which patients from whom the sensitive organism has been isolated serve as the control group). [17][18][19][20][21] Despite increased linezolid usage, international surveillance data still show a relatively low incidence of linezolid-resistant Enterococcus, with a prevalence rate of 2% or less, and reports of linezolid-resistant VRE are limited to case reports and institutional outbreaks. [1][2][3][4][5][6][11][12][20][21][22][23] However, in our hospital, microbiological data showed a much higher prevalence of linezolid resistance among Enterococcus isolates, at 9.8%, and in this study we found the prevalence of linezolid resistance among VRE isolates to be 20%.…”

“…[17][18][19][20] We decided against doing this because we noted that, in the resistant case group, 12 patients had the organism isolated during the first 2 days of their hospital stay; that is, their time at risk was less than 48 hours. We felt that if we had excluded these patients from our control group it would have subtracted from the accuracy of our source population.…”

“…17,18 In this study, the same control group was used for the 2 concurrent retrospective case-control studies at the University of Pittsburgh Medical Center, Presbyterian Hospital. This was considered the appropriate control group selection, as both case groups were from the same source population.…”

Treatment with Fluoroquinolones or with β-Lactam-β-Lactamase Inhibitor Combinations Is a Risk Factor for Isolation of Extended-Spectrum-β-Lactamase-Producing Klebsiella Species in Hospitalized Patients

“…This may have created selection bias, which may have generated distorted effect estimates of association between resistance and antibiotic utilization (14,16,17). Alternatively, the case-case-control study design contrasts two separate case-control analyses within a single study, which enables more accurate identification of risk factors for antimicrobialresistant pathogens (21). Thus, for example, one is able to identify variables specifically predictive of ESBL-producing Klebsiella spp.…”