Opioid analgesics and the risk of serious infections

Abstract

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.