Background: Recent reports of necrotizing fasciitis in children with varicella who received a nonsteroidal antiinflammatory drug (NSAID) recall earlier concerns regarding the possibility of relationships between infections and NSAIDs. We searched the Food and Drug Administration's Spontaneous Reporting System (SRS) for necrotizing soft tissue infections reported in conjunction with the use of NSAIDs, to identify common features.
Methods: A computer search of NSAID listings in the adverse event database recovered reports with codes for selected infection and necrosis-related diagnostic categories. From review of individual reports classified under these codes, cases were selected if the terms "necrotizing fasciitis," "necrotic," or "gangrenous" appeared in the adverse drug reaction description. Demographic, drug use, and disease course information were gathered.
Findings: Thirty-three cases were identified, of which 10 were fatal. Over two-thirds of the patients were younger than 40 years. Thirty (91%) had a possible portal of entry for infection. Most received NSAIDs for acute conditions including varicella, trauma, and postoperative or postpartum pain; 7 received an NSAID by intramuscular injection. Specific NSAIDs accounting for most reports were also among those likely to be most heavily used in the relevant populations.
Interpretation: Common features of these rare case reports of necrotizing soft tissue infections with NSAID use include characteristics such as age, portal of infection entry, indication for NSAID use, route of administration, and individual NSAIDs. The total number of SRS cases does not suggest that necrotizing infection is frequent with NSAIDs or likely without other risk factors. Controlled observational studies would help to define any causal contribution of these factors to the evolution of severe infection.