Prescription opioid use was strongly associated with an increased risk for laboratory-confirmed pneumonia, meningitis, and other invasive pneumococcal diseases (IPD), with the most robust associations seen in users of long-acting, high-potency opioid pain relievers, researchers reported.
In a retrospective cohort study of enrollees in TennCare — Tennessee’s Medicaid program — those with IPD had a 62% greater odds of being current opioid users compared with controls without confirmed IPD, according to Andrew Wiese, PhD, of Vanderbilt University Medical Center, in Nashville, and colleagues.
These findings, along with earlier research also showing opioid use to be a risk factor for pneumococcal infection, have implications for healthcare providers and their patients, they wrote in the Annals of Internal Medicine.
“Because the strongest associations were observed for opioids with certain characteristics, these findings should be considered when selecting opioid analgesics for pain management,” they stated.
Wiese told MedPage Today that clinicians should be especially careful when making treatment decisions in patients with a high risk for infections. “The implication for prescribing physicians is that they should consider these findings when choose whether to treat with opioid analgesics in the first place, and also when considering the type of opioid formulation to prescribe, especially among individuals already at high risk for infections, such as older adults,” he said.
The nested case-control study included 1,233 children and adults with confirmed IPD infections between 1995 and 2014. They were matched to 24,399 controls without confirmed IPD during the time period.
Opioid use was assessed based on pharmacy prescription fills, and invasive pneumococcal disease was defined by the isolation of Streptococcus pneumoniae from a normally sterile site.
“The odds of current opioid use were compared between the case and control groups, accounting for known IPD risk factors. Secondary analyses categorized opioid use by opioid characteristics, applied an IPD risk score to assure comparability between exposure groups, and analyzed pneumonia and non-pneumonia IPD cases separately,” the researchers wrote.
They reported that the case patients had a greater odds of being current opioid users (adjusted odds ratio 1.62, 95% CI 1.36-1.92). Current users of long-acting opioids had an 87% increased adjusted risk (aOR 1.87, 95% CI 1.24-2.82).
Risk was also increased for users of high potency opioids (aOR 1.72, 95% CI 1.32-2.25) and for users who took high doses:
- 50 to 90 morphine mg equivalent/d: aOR 1.71 (95% CI 1.22-2.39
- ≥90 morphine mg equivalents/d: aOR 1.75 (95% CI 1.33-2.29)
The results were similar when the IPD risk score was considered, and when pneumonia and other infections were analyzed separately.
“A unique strength of our study was the use of ABCs data to identify laboratory-confirmed IPD cases,” the researchers wrote. “We minimized misclassification by using only laboratory-confirmed outcomes. The specificity of laboratory-confirmed IPD is very high, supporting its use in assessing relative measures of association.”
Study limitations included the reliance on pharmacy prescription fills to assess opioid use and the possibility of residual confounding.
In a 2011 study, Sascha Dublin, MD, PhD and Michael Von Korff, ScD, of Seattle’s Kaiser Permanente Washington Health Research Institute showed current opioid use to be associated with a 38% greater risk for community-acquired pneumonia compared to non-use in older adults.
In 2016, Wiese’s group reported that opioid use was associated with more serious infections in a study of patients with rheumatoid arthritis.
“The results from the three studies are remarkably consistent; all observed higher risks among new users and persons using immunosuppressive or long-acting opioids,” Dublin and Von Korff wrote in an Annals accompanying editorial. “The studies spanned a range of populations, strengthening the generalizability of their findings. Although pneumonia was the predominant infectious outcome observed in all three studies, two also found associations between opioid use and other infections.”
Dublin and Von Korff wrote that, taken together, the studies “provide cautionary evidence of a higher infection risk with prescription opioids, suggesting the need for prudent steps to protect patients even though uncertainties remain.”
They noted that studies are urgently needed to answer critical questions, including whether both new and long-time use of prescription opioids involves an increased IPD risk, if risk wanes with long-time use, and if specific opioid medications carry more risk than others.
“While awaiting more definitive answers, we must reconsider the risks and benefits of opioids,” the editorialists wrote. “The current widespread use of these drugs in the United States is not based on adequate research establishing either their effectiveness or their safety. Reflexive and poorly monitored prescribing of opioid analgesics on the untested assumption that patient outcomes are improved may be harming more patients than we care to admit.”
The study was funded by the NIH.
Wiese disclosed no relevant relationships with industry. Co-authors disclosed relevant relationships with Merck, Pﬁzer, Dynavax, Seqirus, Sutrovax, Shionogi, the NIH, Sanoﬁ-Pasteur, the Campbell Alliance, the CDC, the FDA, and the Agency for Healthcare Research and Quality.
Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner