Background: The success of the increasing number of arthroplasty, spinal instrumentation and other implanted orthopaedic devices is hampered by device-related infections. More than half of these infections are caused by staphylococcal biofilm mediated antibiotic resistance. The hope of preventing prosthetic joint infection by antibiotic loaded cement is threatened by emerging resistant organisms. No bacterial resistance to betadine has been reported.

Current intervention strategy is focussed on prevention of initial device colonisation and inhibition of genes encoding biofilm formation.

Aim:

Determine the minimum inhibitory concentration (MIC) of betadine.

Methods: MIC of betadine for both reference strains and strains isolated from infected orthopaedic implants was determined. Biofilm assay was performed at different betadine concentrations using 96-well polystyrene plates.

Total RNA for cDNA synthesis was isolated from bacterial at different twofold dilutions of betadine concentrations.

Real time polymerase chain reaction was used to quantify effects of betadine on gene expression pattern of the icaADBC operon using the constitutively expressed gyrB gene as internal control.

Bacterial was cultivated on polystyrene plates coated with different sub-inhibitory and clinical in-use doses of betadine to assess surface adherence.

Results: The MIC of betadine was 1.4% for all bacterial strains. Clinical in-use doses of betadine prevented biofilm formation.

A step-wise reduction of biofilm was observed at increasing sub-inhibitory doses of betadine (p< 0.0001).

IcaA expression correlated with biofilm formation in staphylococcal organisms. Decrease in icaA expression was strongly associated with an increase in expression in the biofilm repressor gene, icaR.

The repressive effect of betadine on biofilm formation by Staphylococcal bacteria is by a separate mechanism from its bacteriostatic mechanism of action.

Conclusion: This study shows that icaR is a potential therapeutic target through which the ability of Staphylococcal bacterial to form biofilm may be reduced. Sub-inhibitory dose of betadine inhibited biofilm formation.

Prevention of bacterial surface attachment as demonstrated by this study is suggestive that these compounds could be developed as a surface coating agents for orthopaedic implants.