Synergistic effect of immunomodulatory S100A8/A9 and ciprofloxacin against Pseudomonas aeruginosa biofilm in a murine chronic wound model.
Pathog Dis
; 78(5)2020 07 01.
Article
em En
| MEDLINE
| ID: mdl-31116394
ABSTRACT
The majority of chronic wounds are associated with bacterial biofilms recalcitrant to antibiotics and host responses. Immunomodulatory S100A8/A9 is suppressed in Pseudomonas aeruginosa biofilm infected wounds. We aimed at investigating a possible additive effect between S100A8/A9 and ciprofloxacin against biofilms. MATERIALS/METHODS:
Thirty-two mice were injected with alginate-embedded P. aeruginosa following a third-degree burn. The mice were randomized into four groups receiving combination ciprofloxacin and S100A8/A9 or monotherapy ciprofloxacin, S100A8/A9 or a placebo and evaluated by host responses and quantitative bacteriology in wounds. In addition, in vitro checkerboard analysis was performed, with P. aeruginosa and ascending S100A8/A9 and ciprofloxacin concentrations.RESULTS:
S100A8/A9 augmented the effect of ciprofloxacin in vivo by lowering the bacterial quantity compared to the placebo arm and the two monointervention groups (P < 0.0001). S100A8 and 100A9 were increased in the double-treated group as compared to the monointervention groups (P = 0.032, P = 0.0023). Tissue inhibitor of metalloproteinases-1 and keratinocyte\chemokine chemoattractant-1 were increased in the double-intervention group compared to the S100A8/A9 group (P = 0.050, P = 0.050). No in vitro synergism was detected.CONCLUSION:
The observed ciprofloxacin-augmenting effect of S100A8/A9 in vivo was not confirmed by checkerboard analysis, indicating dependence on host cells for the S100A8/A9 effect. S100A8/A9 and ciprofloxacin is a promising therapy for optimizing chronic wound treatment.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
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Infecção dos Ferimentos
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Ciprofloxacina
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Biofilmes
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Calgranulina A
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article