Abstract
Introduction: One of the most important mechanisms S. epidermidis uses to establish infection on biomaterials is biofilm formation, in which adhesion and the production of polysaccharide intercellular adhesin (PIA) are key factors. Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to inhibit S. epidermidis biofilm formation and may be useful in prevention or treatment of implant infections (1,2). The potential of these drugs was evaluated by determining the effects of the NSAIDs on bacterial growth, adhesion to bare and conditioned polymethyl-methacrylate (PMMA), on biofilm development, and on established biofilms.
Methods: A PIA-deficient mutant and wild type strain (gift of Prof. D. Mack, Hamburg) and 3 clinical isolates of S. epidermidis were used. The NSAIDs were salicylic acid, acetylsalicylic acid, ibuprofen and phenylbutazone. Their effects on bacterial growth rate and viability were assessed. For adhesion assay, bacteria were exposed to a 1mM concentration of each drug and allowed to adhere for 1h to bare or human plasma – conditioned PMMA before being sonicated and quantified by chemiluminescence and culture. For biofilm assays, bacteria were grown on silicone discs in the presence of various drug concentrations for 4 days before being sonicated and quantified as above. Mature (4 day) biofilms were also exposed to the drugs for a further 4 days and quantified similarly, to assess the effect on established biofilms.
Results: All NSAIDs tested significantly (P< 0.05) reduced the growth rate and viability of each strain, in a concentration – dependent manner. Reduction of adhesion was observed on bare PMMA suggesting interference with either vitronectin – binding protein or charge / hydrophobic interactions. This was independent of the effect on growth. However, adhesion to plasma – conditioned PMMA, presumably mediated by MSCRAMMs, was not significantly affected. Reduction of biofilm formation was observed for all strains and was concentration – dependent, suggesting that inhibition of PIA synthesis was not responsible. There was a significant effect on established biofilms, this was also concentration dependent.
Conclusions:
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All four NSAIDs reduced S. epidermidis growth rate and viability, but at concentrations above those achievable therapeutically.
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The effect on adherence was confined to unconditioned PMMA.
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The effect on biofilm formation and on established biofilms appeared to be related to that on growth and viability.
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On these grounds, NSAIDs appear to have a limited prospect for use in prevention or treatment of S. epidermidis biomaterial-related infection. However, catheter coating, NSAID-antibiotic combinations, and potential for other types of infection may have greater prospects.
Correspondence should be addressed to Dr Carlos Wigderowitz, Honorary Secretary of BORS, Division of Surgery & Oncology, Section of Orthopaedic & Trauma Surgery, Ninewells Hospital & Medical School Tort Centre, Dundee, DD1 9SY.
References:
1 Muller E, Al-Attar J, Wolff A, Farber B (1998). Mechanism of salicylate – mediated inhibition of biofilm in Staphylococcus epidermidis. J Infect Dis177: 501–503. Google Scholar
2 Farber B, Wolff A (1992). The use of nonsteroidal anti-inflammatory drugs to prevent adherence of Staphylococcus epidermidis to medical polymers. J Infect Dis166:861–865. Google Scholar
