Effects of subinhibitory concentrations of vancomycin or cefamandole on biofilm production by coagulase-negative staphylococci

The density of the biofilm layer produced on a plastic surface by 23 clinical isolates and 1 reference strain of slime-positive, coagulase-negative staphylococci was measured following growth in subinhibitory concentrations (sub-MICs) of cefamandole or vancomycin ranging from 2 to 0.008 micrograms/ml. All strains were susceptible to less than or equal to 2 micrograms of each agent per ml. The mean biofilm density produced by each strain was calculated from a total of eight determinations at each sub-MIC and was compared with the mean biofilm density of a drug-free control after correcting for differences in growth. The results showed that the density of the biofilm layer produced by 10 (42%) of 24 strains and 13 (54%) of 24 strains was significantly increased (P less than 0.006) at one or more sub-MICs of cefamandole or vancomycin, respectively. In contrast, the density of the biofilm produced by 9 (38%) of 24 and 2 (8%) of 24 strains was significantly reduced at one or more sub-MICs of cefamandole and vancomycin, respectively, and the biofilm density of 7 of these strains was decreased only when the sub-MIC was one-half the MIC. The biofilm density of six strains (five versus cefamandole and one versus vancomycin) was both enhanced and reduced by different sub-MICs of the same agent. None of the strains produced a detectable biofilm at or above the MIC for the strain. These data indicate that antimicrobial agents such as cefamandole or vancomycin could potentially enhance the biofilm matrix produced by certain slime-positive, coagulase-negative staphylococci on the surface of a biomedical implant if concentrations of these agents fall below the MIC for the infecting strain.