Prescription Opioids Increase Risk for Serious Infections

Bridget M. Kuehn

February 12, 2018

Opioid medications, particularly long-acting or high-dose opioids, may increase the risk for serious infections, including invasive pneumonia, meningitis, and bacteremia, according to a study published online February 13 in the Annals of Internal Medicine.

Animal studies have shown that some opioid medications have immunosuppressive effects. The drugs interfere with the production of bacteria-killing immune cells, reduce the innate immune response, and inhibit the production of antibodies and cytokines. Previous human studies have shown that opioid medications increase the risk for infection in hospitalized patients after surgery or during treatment for burns or cancer. Other studies suggest an increased risk for serious infections in certain high-risk outpatients.

Now, the new study strengthens the evidence that the immune-suppressing effects of opioids extend to humans.

"[W]e found that current opioid use was strongly and consistently associated with the risk for [invasive pneumococcal disease (IPD),] and that the association was strongest for long-acting and high-potency formulations, opioids previously described as immunosuppressive, and high-dose opioids," write Andrew Wiese, PhD, from the Department of Health Policy at Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues.

In the study, Wiese and colleagues analyzed opioid prescriptions for Medicaid patients in Tennessee and linked those data to laboratory-confirmed cases of IPD in the Active Bacterial Core surveillance system. The study included 1233 patients with IPD who were at least 5 years old and 24,399 matched control patients. Patients with IPD had higher odds of current opioid use than control patients (adjusted odds ratio [aOR], 1.62; 95% confidence internal [CI], 1.36 - 1.92). The associations were even stronger for long-acting (aOR, 1.87; 95% CI, 1.24 - 2.82), high-potency (aOR, 1.72; 95% CI, 1.32 - 2.25), and high-dose (aOR, 1.71 - 1.75, depending on dose range) opioids.

One limitation of the study is that it did not measure actual opioid use, only prescriptions for the drugs. Patients with IPD were more likely than control patients to have been vaccinated with the pneumococcal polysaccharide vaccine; this may suggest that the infection risk for opioids is actually higher than the study estimated because some patients in the case group may have received some protection from the vaccine. The authors note that it is unlikely that unmeasured confounding factors contributed to their results because such a factor would have to be unusually strong, with an odds ratio of 2 or greater.

In an accompanying editorial, Sascha Dublin, MD, PhD, and Michael Von Korff, ScD, from Kaiser Permanente Washington Health Research Institute in Seattle, note the results of the human studies to date have been remarkably consistent, and that there is an urgent need for studies looking at the infection risks associated with individual opioid drugs.

In the meantime, both the study authors and the editorialists argue for more judicious use of opioids and careful monitoring for infections in patients using opioids.

"Opioid prescribing should be consistently cautious and closely monitored among all patients, especially those at increased risk for infections, who may be particularly susceptible to harm," the editorialists write. "Before prescribing an opioid, the clinician should carefully consider all reasonable alternative approaches to pain relief. It now seems that decision making also should take into account the risk for serious infections."

Some study authors report personal fees or grants from Merck, Pfizer, Dynavax, Sequirus, Sutrovax, Shinogi, Sanofi-Pasteur, and Campbell Alliance. Editorial authors report grants from Pfizer and Campbell Alliance, and possibly future grant funding from Jazz Pharmaceuticals.

Ann Intern Med. Published online February 13, 2018. Article, Editorial

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