The roles of injury and nonsteroidal anti-inflammatory drugs in the development and outcomes of severe group A streptococcal soft tissue infections

Abstract

Purpose of review This review summarizes clinical and basic science evidence linking trauma and nonsteroidal anti-inflammatory drug (NSAID) use to initiation and progression of severe group A streptococcal (GAS) soft tissue infection. Recent findings New evidence includes recent clinical series and controlled studies that lend support to an NSAID/GAS association, basic science studies that demonstrate unique roles for nonpenetrating injury and NSAID administration in initiation of cryptogenic GAS infection and experimental studies showing that nonselective NSAIDs accelerate disease progression and limit antibiotic efficacy in established GAS soft tissue infections. Potential mechanisms for these processes are discussed. Summary NSAIDs are important anti-inflammatory and analgesic drugs; however, new experimental data suggest that nonselective NSAIDs do more than simply mask the signs and symptoms of developing GAS infection. A more thorough understanding of the triadic interplay of injury-triggered immune signaling, GAS soft tissue infection and NSAIDs is of significant clinical importance and could shift the current paradigm of pain management to avert the consequences of such devastating infections.

The role of nonsteroidal anti‐inflammatory drugs intramuscular injection in the development and severity of deep soft tissue infection in mice

“…In this study, although DS demonstrated an antibacterial effect with a concentration of 40 mg/L, it was not detected at 0.4 mg/L. Also, 0.4 mg/L concentration of DS has an anti‐inflammatory effect in mice . The concentration of injected fluid that contains DS into muscle was 25 mg/ml which is too high for a bacteria to remain alive.…”

“…Stevens [16] has affirmed that NSAIDs may predispose to severe STIs. Later, their findings were supported by some studies about the oral administration of ibuprofen for varicella in the animal model [6,[17][18][19]. However, the relationship between NSAIDs and severe STI still remains controversial [13,20].…”

NSAIDs: can the presence of infectious agent influence the choice of analgesic drug?

“…Data inreference sources are insufficient for ibuprofen and ketorolac: controlled studies [1] detected acceleration of the progression of the soft tissue infections of streptococcal etiology (group A) at their application, as well as reduction of the effectiveness of etiotropic antibiotic therapy. Within our study ketorоlaс and ibuprofen showed no antimicrobial activity against S. mutans (the latter, according to our data, in general, was less sensitive to the inhibitory effects of NSAIDs), but were effective (more pronounced for ibuprofen) against S. pyogenes, which is known to have a high sensitivity to antimicrobial agents of different groups and slowly develop resistance to them.…”

“…On the one hand, acceleration of progression of soft tissue infections of streptococcal etiology (group A) at the application of certain non-selective (ketorolac, ibuprofen and indomethacin), but not COX-2 selective NSAIDs and reduction of efficiency of etiotropic antibiotic therapy were found [1]. On the other hand, in vitro, sodium diclofenac was detected to show antibacterial activity against antibiotic-sensitive and antibiotic-resistant strains of microorganisms, including mycobacteria, associated by the authors with the violation of the DNA synthesis of sensitive flora [2], in addition, antimycobacterial properties of diclofenac have been confirmed in an experiment in vivo [3].…”

Familial Transmission of emm12 Group A Streptococcus

“…The role of these drugs in streptococcal infection outcome is frequently discussed; they seem to cause an increase of severe infection, most probably in children ( 10 ). …”