Unveiling a potential link: Do non-steroidal anti-inflammatory drugs modulate resistance-associated microbial pathways?

Antimicrobial resistance (AMR) remains a significant health concern worldwide, traditionally attributed to inappropriate antibiotic use. Emerging experimental and observational evidence suggests that non-antibiotic medications, including non-steroidal anti-inflammatory drugs (NSAIDs), may influence microbial behavior and adaptive responses associated with reduced antibiotic susceptibility. Beyond their analgesic and anti-inflammatory effects, certain NSAIDs have been shown to modulate bacterial stress responses, efflux pump activity, biofilm dynamics and horizontal gene transfer under specific experimental conditions. This review examines the interplay between NSAIDs and the microbial ecosystem, focusing on resistance-associated mechanisms in antibiotic resistance and discusses implications for microbiome homeostasis and therapeutic outcomes. An extensive literature review was conducted using electronic databases “Google Scholar,” “PubMed,” and “Scopus” to identify relevant studies published between 1990 and 2025. The search strategy employed predefined keywords, including “non-antibiotic drug resistance,” “NSAIDs,” “microbial adaptation,” and “biofilm modulation.” Retrieved records were screened at the title and abstract level, followed by full-text evaluation of eligible studies. Experimental, clinical and mechanistic studies examining NSAID–microbe interactions in relation to antimicrobial resistance were included, while non-English articles and studies lacking microbiological relevance were excluded. The selected literature was qualitatively synthesized to inform the thematic analysis of the mechanisms, clinical consequences and research gaps highlighted in this paper. Preclinical research suggests that NSAIDs including ibuprofen, diclofenac and salicylic acid may modulate microbial survival strategies by reducing antibiotic susceptibility, enhancing biofilm-associated tolerance and altering pathogen behavior. These effects appear to assist adaptive responses associated with resistance-related phenotypes, rather than directly causing antimicrobial resistance. Given the predominantly experimental nature of current evidence, their inclusion in AMR surveillance and stewardship should be approached cautiously and supported by further research.