The relationship between inhibition of bacterial adhesion to a solid surface by sub-MICs of antibiotics and subsequent development of a biofilm

Abstract

Many studies have demonstrated that subminimal inhibitory concentrations (sub-MICs) of antibiotics can inhibit initial microbial adherence to medical device surfaces. It has been suggested that, by inhibiting initial adhesion, biofilm formation might be prevented. However, since initial adherence and subsequent biofilm formation may be two distinct phenomena, conclusions regarding the effects of sub-MIC antibiotics on initial adhesion cannot be extrapolated to biofilm formation. In this study, we evaluated the adherence of several clinical isolates of coagulase-negative staphylococci (CoNS) to acrylic and the effect of sub-MICs of vancomycin, cefazolin, dicloxacillin and combinations of these antibiotics on adherence and biofilm formation. Most of the antibiotics used resulted in effective reduction of bacterial adherence to acrylic, in some cases reaching over 70% inhibition of adherence. When strains with a high biofilm-forming capacity were grown in sub-MICs of those antibiotics, there existed combinations of the drugs that significantly inhibited biofilm formation. However, most of the antibiotic combinations that inhibited adherence did not have a profound effect on biofilm formation. When comparing the results of the effect of sub-MIC amounts of antibiotics in inhibiting adherence with their effect on the inhibition of biofilm formation, significant differences were found, mainly when using combinations of antibiotics. In general, the effect on the inhibition of adherence was greater than the effect on inhibiting biofilm formation. These results demonstrate that assays evaluating the inhibition of initial adherence to medical surfaces cannot fully predict the effect on inhibition of biofilm formation.

Effects of Growth in the Presence of Subinhibitory Concentrations of Dicloxacillin on Staphylococcus epidermidis and Staphylococcus haemolyticus Biofilms

“…Previous reports suggested that the use of sub-MIC concentrations of antibiotics could increase biofilm formation (35). However, more recent studies demonstrated that sub-MIC concentrations of some antibiotics are effective for reducing the amount of biofilm formed (6,17,34,43), which may have some clinical interest. However, other changes that can occur in the physiology of biofilm cells might compromise the general use of this strategy to prevent biofilm formation.…”

“…The concentration of dicloxacillin used in this study was 8 g/ml, which is a sub-MIC concentration, as determined in a previous study (6). Bacterial growth parameters were determined by monitoring the increases in the optical densities at 640 nm of cell suspensions grown in TSB in the presence and absence of dicloxacillin.…”

“…Many studies have demonstrated that low concentrations of antibiotics can inhibit, to some extent, biofilm formation on medical device surfaces (6,33). One of the prophylactic strategies that are currently used is to provide a constant flow of a subinhibitory (sub-MIC) concentration of antibiotic (17).…”

Application of Scanning Electron Microscopy for the Morphological Study of Biofilm in Medical Devices

“…Dicloxacillin is the antibiotic that found to prevent the adherence to the greatest extent when it is used alone at 1/2 of the MIC (Cerca et al, 2005). Also clindamycin at subinhibitory concentrations inhibits the adherence of Pseudomonas aeruginosa, Staphylococcus aureus, Bacteroids spp., Escherichia coli to bone surfaces (Lambe et al, 1987).…”

Effects of Azithromycin in Combination with Vancomycin, Daptomycin, Fosfomycin, Tigecycline, and Ceftriaxone on Staphylococcus epidermidis Biofilms

“…Yet the action of antimicrobial substances on biofilm density and bacterial growth and the interplay of bacteria, surfaces, antimicrobials at differential concentrations, and the host interfering with leukocytes, platelets, red blood cells, and fibrin-either combating or enhancing the bacterial resistance within the biofilm-is still controversial. Although adhesion may be reduced by coating surfaces with antibiotics or silver, biofilm formation and the subsequent infection of the implant are not predictable, as shown in experimental and clinical studies (4,11).…”