For several years, regional pharmacovigilance centers have been warning about the risk of worsening bacterial skin or lung infections caused by Streptococcus pyogenes or Pneumococcus after taking non-steroidal anti-inflammatory drugs (NSAIDs), particularly ibuprofen. A new report submitted to the French Medicines Agency in 2024 documented 216 cases of serious bacterial infections (162 with ibuprofen, 54 with ketoprofen) over 4.5 years following the use of NSAIDs for fever or acute pain. This represents about 21% of serious adverse events with ibuprofen (8% with ketoprofen). Streptococcal infections were most common with ibuprofen (62% of serious bacterial infections
44% with ketoprofen). These streptococcal infections were invasive (97%) and included severe sepsis/toxic shock, pleuropneumopathy, meningitis/meningoencephalitis and necrotizing dermohypodermatitis. Pharmacoepidemiological studies all suggest an association between NSAID exposure and an increased risk of pleuropulmonary complications, with estimated risks ranging from 1.8 to 8. Several mechanistic data also suggest a specific adverse effect on the severity of invasive streptococcal infections through a specific intrinsic effect of NSAIDs on the enhancement of streptococcal diffusion (via vimentin). Experimental studies in animals have also demonstrated this risk, even when NSAIDs are combined with antibiotics. In conclusion, in the presence of a streptococcal infection, whether diagnosed or not, taking an NSAID for fever or acute pain, even for a short time and even in association with an antibiotic, is a risky practice. It encourages the development of a more serious streptococcal infection, not only by delaying management of the infection, but more importantly by promoting the dissemination of the streptococcus. As invasive S. pyogenes infections are a real public health problem, any potential risk factor for aggravation must be taken into account.