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Pneumonia Due to Legionella pneumophila in Patients Treated With Tumor Necrosis Factor-α Antagonists

Sorbello, Alfred DO, MPH; Diak, Peter PharmD, MPH; Gilbert, Jane MD, PhD; Boucher, Robert MD, MPH

Infectious Diseases in Clinical Practice: November 2011 - Volume 19 - Issue 6 - p 399-405
doi: 10.1097/IPC.0b013e31821bc8f9
Original Articles

Background: Tumor necrosis factor-α antagonists (anti-TNFα) are biologic agents that alleviate chronic inflammatory disorders by reducing the proinflammatory effects of TNFα. By neutralizing TNFα, they also impede its immunoregulatory properties leading to increased susceptibility to infection. In this study, we evaluated Food and Drug Administration (FDA) postmarket data for evidence of a potential association between anti-TNFα and Legionella pneumonia.

Methods: We retrieved all US serious adverse event reports of Legionella pneumonia in anti-TNFα-treated patients submitted to the FDA Adverse Event Reporting System between 1999 and 2010. We analyzed only the reports in which the methods used to detect Legionella infection were described. We also reviewed case reports published in the literature.

Results: We analyzed reports from the Adverse Event Reporting System for 30 patients given infliximab (73%), etanercept (17%), or adalimumab (10%) who developed Legionella pneumonia. Their median age was 52 years (range, 25-85 years); 60% were female, 73% had rheumatoid arthritis, and 83% received concomitant immunosuppressives. Legionella pneumophila (Lp) serogroup 1 detected by urine antigen accounted for 73% of the cases. One patient was infected with Lp serogroup 4 and Lp serogroup 10. There was insufficient information to characterize the infecting species for the remaining patients. Four patients (13%) died. Comparable clinical characteristics and outcomes were noted in published case reports.

Conclusions: The FDA postmarket data demonstrate that L. pneumophila is an important opportunistic pathogen in anti-TNFα-treated patients. Although a causal relationship could not be established because of confounding from concomitant immunosuppressives, increased awareness of Legionella pneumonia is advised because of the risk for serious outcome.

Infectious complications have been reported in patients receiving tumor necrosis factor-α antagonists (anti-TNFα). Based on postmarketing data from the FDA Adverse Event Reporting System, Sorbello et al. report 30 anti-TNFα treated patients who developed Legionella pneumonia. Additional case reports were identified from the scientific literature. Although a causal association could not be established due to confounding from concomitant immunosuppressive drugs, heightened awareness of pneumonia due to Legionella pneumophila is advised due to the risk for serious outcome.

From the Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.

Correspondence to: Alfred Sorbello, DO, MPH, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD 20993. E-mail: alfred.sorbello@fda.hhs.gov.

The authors have no funding or conflicts of interest to disclose.

Presented in part at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy, September 15, 2010, Boston, Mass.

The views expressed in this report are those of the authors and do not necessarily represent the views of the US Food and Drug Administration.

© 2011 Lippincott Williams & Wilkins, Inc.