Prescribed Opioid Use and Infection Risk in Patients With Cancer and Treatment-Associated Neutropenia

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In a German study reported in a research letter in JAMA Internal Medicine, Jakob et al found that prescribed opioid use did not appear to increase risk of infection in hospitalized patients with cancer who developed treatment-associated neutropenia. According to the investigators, recent data have suggested an increased risk of infection with opioid use in immunocompromised patients. 

Study Details

The study was a nested case-control study of data from patients with cancer from the Cologne Cohort of Neutropenic Patients. Patients had developed an absolute neutrophil count < 500/μL during cancer treatment given between January 2008 and December 2018.

Case patients were in-patients with hospital-acquired infection (fever ≥ 100.4°F, blood stream infection, pneumonia, or intensive care unit admission) and no baseline infection; control patients did not develop infections. In total, there were 2,135 patient-control pairs matched by age (within 5 years), sex, underlying disease, and time of admission (within 1 year). Adjusted odds ratios (aORs) were from multivariate analysis.

Infection Risk

A total of 371 patient cases (17.4%) and 354 patient controls (16.6%) received opioids.


  • Use of prescribed opioids with or without immunosuppressive properties did not appear to increase infection risk in neutropenic patients.
  • Findings were similar when only incidence of pneumonia was considered.

Patients using opioids with known immunosuppressive properties (ie, diamorphine, dihydrocodeine, fentanyl, morphinhydrochloride, morphine sulfate, sufentanil, or sufentanil citrate) accounted for 6.0% of infection cases vs 6.8% of controls (aOR = 0.84, P  = .22). Those using opioids with no immunosuppressive properties (ie, buprenorphine, hydrocodone, hydromorphone, oxycodone, oxycodone/naloxone, or tramadol) accounted for 9.0% cases vs 8.7% of controls (aOR = 1.11, P = .43). Those receiving agents with unknown immune effects (ie, levomethadone, methadone, meperidine, tapentadol, piritramide, tilidine, or tilidine/naloxone) accounted for 2.3% of cases vs 1.0% of controls (aOR = 2.59, P < .001). Meperidine accounted for most opioid use in the latter category (33 of 50 cases, 14 of 22 controls); as stated by the investigators, “an association of infection with meperidine use is probably based on this drug being a standard treatment for severe mucositis, an acknowledged infection risk.”

Results were similar to the overall analysis when only pneumonia (1,072 patient cases) was included as an infection endpoint (aOR = 1.00, 95% confidence interval [CI] = 0.75–1.34, for opioids with immunosuppressive properties; aOR = 1.10, 95% CI = 0.79–1.53, for opioids without immunosuppressive properties).

The investigators concluded, “In our analysis, we were not able to identify an increased risk for pneumonia or any infection by any type of opioid in severely immunocompromised patients…. [F]urther observation, ideally in a controlled prospective trial, is warranted before adapting current standards in cancer care.”

Jörg Janne Vehreschild, Dr Med, of the Department of Internal Medicine, Hematology, and Oncology, Goethe University Frankfurt, is the corresponding author for the JAMA Internal Medicine article.

Disclosure: For full disclosures of the study authors, visit

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