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Pneumonia Due to Legionella pneumophila in Patients Treated With Tumor Necrosis Factor-&agr; Antagonists

Background:Tumor necrosis factor-&agr; antagonists (anti-TNF&agr;) are biologic agents that alleviate chronic inflammatory disorders by reducing the proinflammatory effects of TNF&agr;. By neutralizing TNF&agr;, 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-TNF&agr; and Legionella pneumonia. Methods:We retrieved all US serious adverse event reports of Legionella pneumonia in anti-TNF&agr;-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-TNF&agr;-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.