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In-vitro study of the synergistic effect of an enzyme cocktail and antibiotics against biofilms in a prosthetic joint infection model

(2021) Antimicrobial Agents and Chemotherapy — Vol. 65, n° 4, p. e01699-20 [1-24] (2021)

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Abstract
Prosthetic Joint Infections (PJI) are frequent complications of arthroplasties. Their treatment is made complex by the rapid formation of bacterial biofilms, limiting the effectiveness of antibiotic therapy. In this study, we explore the effect of a tri-enzymatic cocktail (TEC) consisting of an endo-1,4-β-D-glucanase, a β-1,6-hexosaminidase, and an RNA/DNA non-specific endonuclease combined with antibiotics of different classes against biofilms of S. aureus, S. epidermidis, and E. coli grown on Ti6Al4V substrates. Biofilms were grown in TSB with 10g/L glucose and 20g/L NaCl (TGN). Mature biofilms were assigned to a control group or treated with the TEC for 30 minutes, then either analyzed or reincubated for 24h in TGN or TGN with antibiotics. The cytotoxicity of the TEC was assayed against MG-63 osteoblasts, primary murine fibroblasts, and J-774 macrophages using the LDH release test. The TEC dispersed 80.3 to 95.2% of the biofilms' biomass after 30 minutes. The reincubation of the treated biofilms with antibiotics resulted in a synergistic reduction of the total culturable bacterial count (CFU) compared to biofilms treated with antibiotics alone in the three tested species (additional reduction from 2 to more than 3 log10 CFU). No toxicity of the TEC was observed against the tested cell lines after a 24h incubation. The combination of pretreatment with TEC followed by a 24h incubation with antibiotics had a synergistic effect against biofilms of S. aureus, S. epidermidis, and E. coli. Further studies should assess the potential of the TEC as an adjuvant therapy in in-vivo models of PJI
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Citations

Poilvache, H., Ruiz Sorribas, A., Cornu, O., & Van Bambeke, F. (2021). In-vitro study of the synergistic effect of an enzyme cocktail and antibiotics against biofilms in a prosthetic joint infection model. Antimicrobial Agents and Chemotherapy, 65(4), e01699-20 [1-24]. https://doi.org/10.1128/AAC.01699-20 (Original work published 2021)