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Title page for ETD etd-11132017-101406

Type of Document Dissertation
Author Wiese, Andrew David
Author's Email Address andrew.d.wiese@vanderbilt.edu
URN etd-11132017-101406
Title Opioid analgesics and the risk of serious infections
Degree PhD
Department Epidemiology
Advisory Committee
Advisor Name Title
Carlos Grijalva Committee Chair
C. Michael Stein Committee Member
Marie Griffin Committee Member
Robert Greevy Committee Member
William Schaffner Committee Member
  • opioids
  • infection
  • pharmacoepidemiology
Date of Defense 2017-11-03
Availability unrestricted
Although certain opioid analgesics have shown immunosuppressive properties in animal experiments, the clinical implications of prescription opioid use on the risk of serious infection among humans are unknown. We conducted a series of epidemiological studies to test the hypothesis that prescription opioid use is an independent risk factor for serious infections and that the association differs across opioid type and dose. In a nested-case control study conducted among subjects enrolled in Tennessee Medicaid (TennCare), we showed that opioid use was strongly and consistently associated with an increased risk of laboratory-confirmed invasive pneumococcal disease (IPD). The observed association was strongest for long-acting and high potency formulations, and for high dose opioids. As laboratory-confirmed IPDs are relatively rare, a separate study was conducted to assess the performance of coding algorithms for identifying hospitalizations for serious infections from TennCare administrative data. Using medical chart reviews as reference, we demonstrated that coded algorithms had a high positive predictive value for identifying true infections, supporting their use in epidemiological studies. Finally, we assembled a retrospective cohort of adults enrolled in TennCare who initiated use of long-acting opioids to compare the risk of serious infection among subjects initiating opioids with previously reported immunosuppressive properties compared to those initiating opioids without known immunosuppressive properties. Hospitalizations for serious infection were identified using our previously validated coding algorithms. The incidence of serious infections was significantly higher among users of opioids with previously described immunosuppressive properties, compared with users of opioids without immunosuppressive properties. These findings complement previous experimental evidence and support the hypothesis that opioid use is a novel, clinically important risk factor for serious infections.
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