Opioids May Boost Pneumococcal Infection Risk

The use of prescription opioids in the United States is a topic that seems to be part of the daily discussions within the medical community, particularly as the number of deaths related to opioids continues to rise.

A study published in the Annals of Internal Medicine this week suggests that opioids may pose a different, unintended untoward consequence in patients: an increased risk of pneumococcal infection. Animal studies have indicated that opioids may possess certain immunosuppressive properties that could increase susceptibility to infection. However, the clinical implications of opioid use in humans had previously been uncertain.

Wiese and collegues performed a retrospective nested case-controlled study funded by The National Institutes of Health of patients managed through the Tennessee Medicaid program in. Patients over the age of 5 years who had filled at least one opioid prescription between 1995 to 2014 were considered for inclusion. Up to 20 control patients without laboratory-confirmed pneumococcal disease were selected for each case patient and matched based on age and county of residence. Approximately 96.4% of patients were over the age of 18. It should be noted that more patients in the case group had other risk factors for pneumococcal infections than the control group. These included chronic heart and lung disease, HIV, diabetes, cancer, and history of tobacco use. However, the statistical analysis of the study was conducted to adjust for these variables.

More case patients were current opioid uses than controls (25.2% vs. 14.4%). Opioid use was significantly associated with invasive pneumococcal infection in patients currently on opioid therapy (adjusted OR 1.62 (1.36-1.92)). The association was significant in both long-acting and short-acting agents, those with medium and high potencies. Daily doses were categorized in terms of morphine milligram equivalents (MME) as < 50 MME/day, 50-90 MME/day, and >90 MME/day. All 3 dose groups showed a significant association with pneumococcal infection.

The majority (73.9%) of pneumococcal disease in case patients was diagnosed as pneumonia. The risk of current opioid use and invasive pneumococcal pneumonia was significant (adjusted OR 1.54 (1.26-1.88). The remaining 26.1% of case patients were diagnosed with meningitis, primary bacteremia or bactermeia secondary to other conditions or infections. There was also an association between current opioid use and pneumococcal infection in non-lung infections (adjusted OR 1.94(1.36-2.77)).

Only 2 other studies have evaluated the potential for a correlation in opioid use and infection. The authors of those studies were also the lead authors of the current study. The study publised in 2011 by Dublin and collegues showed a 38% increased risk of community-acquired pneumonia in geriatric patients taking opioids, with an elevated risk noted in new opioid initiation and with long-acting agents. The 2016 study, also by Wiese and collegues, was limited to patients with rhematoid arthritis, but looked at serius infections broadly. This study found an increased risk of opioid use and serious infections. Like the study by Dublin et al, the risk was elevated with new users and those on long-acting opioids.

The 3 studies show consistent results and suggest that use of opioids may increase a patient's chance for invasive infection. However, the studies vary in their patient populations and some of their findings. Although current use was shown to increase infection risk, whether that risk is the highest at opioid initiation or remains constantly elevated throughout analgesitc treatment has not been definatively determined. Further data are needed to determine if the risk of infection is truely a class effect or if the results of these studies are primarily driven by any particular opioid(s).

Prospective observation data can help answer these and other questions that have been raised by the authors, but are still largely unanswered. However, additional caution, particularly among patients with other risk factors for infection, would be prudent.

References

1. Wiese AD, Griffin MR, Schaffner W, et al. Opioid analgesic use and risk for invasive pneumococcal diseases: a nested case-control study. Ann Intern Med. doi:10.7326/M17-1907. Available http://annals.org/aim/fullarticle/2672601/opioid-analgesic-use-risk-invasive-pneumococcal-diseases-nested-case-control

2. Dublin S, Wlker RL, Jackson ML, et al. Use of opioids or benzodiazepines and risk of pneumonia in older adults: a population-based case-control study. J Am Geriatr Soc. 2011;59:1899-1907.

3. Wiese AD, Griffen MR, Stein CM, et al. Opioid analgesics and the risk of serious infections among patients with rhematoid arthritis: a self-controlled case series study. Arthritis Rheumatol.2016;68:323-331