The pH-dependent effect of cationic and non-ionic delmopinol on planktonic and biofilm bacteria

The primary purpose was to evaluate the antimicrobial effects of cationic and non-ionic delmopinol on planktonic and biofilm bacteria.

Determination of the minimum inhibitory concentrations on planktonic and biofilm bacteria was performed below and above the pK_a-value of delmopinol. Test bacteria were Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa. Comparisons were made with three antimicrobial agents and "quaternary" delmopinol. Synergy testing of delmopinol was determined with serial dilutions of delmopinol with the other compounds in a checkerboard fashion, and the fractional inhibitory concentration index (FIC) was calculated.

Delmopinol showed minor differences between its MIC- and MBEC-values for all bacterial strains (MBEC/MIC-ratios of 1-2). For the other compounds the difference between their MIC- and MBEC-values were higher and varied considerably between the bacteria. The MIC- and MBEC-concentrations were lower at pH where the non-ionic form of delmopinol dominates. "Quaternary" delmopinol showed the same MIC-concentrations as delmopinol, but needed much higher concentrations to kill biofilm bacteria. Synergy testing showed FIC-indices of 0.5-1.

The biofilm penetration of non-ionic delmopinol is better than for cationic delmopinol. Likewise, the cationic test reference samples exerted limited biofilm penetration. The increased efficacy of non-ionic delmopinol is probably due to reduced binding to negative groups in the extracellular matrix of polymeric substances surrounding biofilm bacteria. It is also proposed that the non-ionised form of delmopinol deposits on the biofilm surface. Higher amounts of delmopinol than expected will therefore accumulate. Combinations of delmopinol with other compounds suggests an additive antimicrobial effect.