N-acetylcysteine as an adjunct to antibiotics against bacterial biofilms: A systematic review of in vitro evidence
Abstract
N-acetylcysteine (NAC) is investigated as an antibiotic adjunct, but acidity, formulation and experimental context complicate interpretation. We evaluated comparative in-vitro evidence while distinguishing biofilm prevention, established-biofilm treatment and resistance evolution. MEDLINE/PubMed, Embase, Scopus and Web of Science were searched through August 2026, with supplementary searching. Extraction distinguished NAC preparation and exposure pH, medium, hydrodynamics, NAC-alone controls, treatment intent and interaction methodology. Results were synthesized by experimental context, regimen, phase and endpoint without pooling or whole-study efficacy voting. Fifty-five studies were included: 7 evaluated combination exposure during formation only, 37 after establishment only, 9 both, and 2 resistance evolution. NAC-alone arms were documented in 39 studies, partial or formulation-specific in 9, and not identified in 7. Only two studies included a continuous-flow model. Selected combinations improved biofilm-associated outcomes, but intrinsic-acidic and neutralized preparations, biomass and viability endpoints, and planktonic versus biofilm interaction tests were not interchangeable. Liposomal and catheter-lock findings differed by dose matching, isolate and control set. Polymyxin findings varied with organism, resistance background, medium and exposure; rifampicin-alone and rifampicin-containing multidrug comparators addressed different questions. NAC is a context-dependent…
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Evidence Hub reads this as a systematic review, done in cell cultures (in vitro), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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