nonsteroidal anti-inflammatory drugs (NSAIDs) in the development and outcomes of severe group A streptococcal (GAS) soft tissue infections

Last edited 12/2022 and last reviewed 12/2022

Group A streptococcal (GAS) necrotizing soft tissue infection

• mortality ranges from 30 to 85%; survivors require aggressive surgical intervention and intensive care management (1)

Experimental evidence suggests NSAIDs actively contribute to initiation of secondary infection after injury, increase severity of established infection and reduce antibiotic efficacy (1,2)

• delay muscle regeneration, increase susceptibility to postinjury GAS infection and dramatically accelerate GAS disease progression in established soft tissue infection (1)
• even short-term exposure to such NSAIDs may reduce antibiotic efficacy (1)
• in an animal study, diclofenac sodium injection prior to bacterial inoculation (GAS) might predispose to bacteremia and sepsis (2)

A review concluded that (3):

• use of nonselective NSAIDs, either alone or as adjuncts to antibiotic therapy, for GAS soft tissue infection may contribute to worse outcomes

Proposed mechanism for more severe GAS soft tissue infection with NSAID

• a) based on the ability of NSAIDs to interrupt the negative feedback loop that limits production of tumor necrosis factor (TNF) alpha - a key mediator of septic shock (3)
• b) some authors argue that NSAIDs merely mask the signs and symptoms of developing infection, such that diagnosis and antibiotic treatment are delayed

Reference:

• Bryant AE, Bayer CR, Aldape MJ, Stevens DL. The roles of injury and nonsteroidal anti-inflammatory drugs in the development and outcomes of severe group A streptococcal soft tissue infections. Curr Opin Infect Dis. 2015 Jun;28(3):231-9.
• Ture Z, Demiraslan H, Kontas O, Alp E, Doganay M. The role of nonsteroidal anti-inflammatory drugs intramuscular injection in the development and severity of deep soft tissue infection in mice. Fundam Clin Pharmacol. 2018 Apr;32(2):147-154.
• Hamilton SM et al. Effects of Selective and Nonselective Nonsteroidal Anti-inflammatory Drugs on Antibiotic Efficacy of Experimental Group A Streptococcal Myonecrosis, The Journal of Infectious Diseases, Volume 209, Issue 9, 1 May 2014, Pages 1429-1435, https://doi.org/10.1093/infdis/jit594