Sub-Inhibitory Concentrations of Rifampicin Strongly Stimulated Biofilm Production in S. aureus

Abstract

Background and Objectives: Staphylococcus aureus is an important pathogen and a frequent cause of infections associated with biofilm production in implantable medical devices. Biofilm production can be induced by sub-inhibitory concentrations (sub-MICs) of certain antibiotics, but few studies have researched this occurrence in S. aureus. In this study, we investigated the effect of sub-MICs of rifampicin and minocycline on biofilm production by five clinical and five non-clinical S. aureus isolates.Methods:Microtiter Plate assay and Congo Red Agar Test were used to analyze the biofilm production. The biofilm composition was evaluated by the detachment assay with sodium metaperiodate and proteinase K.Results:Rifampicin sub-MICs induced very high biofilm formation in seven isolates that were non-producers in Tryptic Soy Broth. In one producer isolate, the biofilm formation level was not affected by sub-MICs of this drug. Sub-MICs of minocycline did not induce biofilm production in all isolates tested and in two producer isolates, instead, MIC/2 and MIC/4 inhibited biofilm production. The results of the drugs in combination were similar to those with rifampicin alone. The biofilm matrix was identified as polysaccharide, except for one producer isolate, classified as proteinaceous. Polysaccharide biofilm producer isolates, when grown on Congo Red Agar without sucrose, but with sub-MICs of rifampicin, showed results in agreement with those obtained in Microtiter Plate Test.Conclusion:The high biofilm production induced by sub-MICs of rifampicin has potential clinical relevance, because this is one of the drugs commonly used in the impregnation of catheters. In addition, it is used adjunctively to treat certain S. aureus infections.

Phenotypic Characterization of Rhodococcus equi Biofilm Grown In Vitro and Inhibiting and Dissolving Activity of Azithromycin/Rifampicin Treatment

“…Long-term RIF monotherapy at sub-inhibitory concentrations (RIF MIC in combination ) did not prevent bacterial biofilm formation. Moreover, in contrast with earlier findings against staphylococcal biofilms [38], RIF did not seem to stimulate biofilm production.…”

Correlation Between Biofilm-Formation and the Antibiotic Resistant Phenotype in Staphylococcus aureus Isolates: A Laboratory-Based Study in Hungary and a Review of the Literature

“… 57 For example, Lima-e-Silva et al reported that in sub-lethal doses (MIC/2 and MIC/4), rifampin strongly stimulated biofilm-formation (when measured by the CRA plate and CV microtiter plate assay), in contrast to minocycline, which did not have such inducing effects. 58 The effects of low antibiotic doses on the biofilm-forming capacity are thought to occur by differential expression of genes of interest due to the noxious agents. 59 The literature has shown that sub-MIC concentrations of tetracycline, quinupristin and dalfopristin were presented as strong inducers, while erythromycin was noted as a weak inducer of ica -gene expression.…”

Antibiotic Tolerance of Staphylococcus aureus Biofilm in Periprosthetic Joint Infections and Antibiofilm Strategies

“…As already known, most antibiotics treatments are not effective against S. aureus biofilms. Worse, several studies have shown that antibiotics treatments can induce biofilm formation [ 61 , 62 ]. For now, rifampicin (rifampin) is the most efficient antibiotic against S. aureus biofilms; presents a good penetration into bone tissues; and shows good efficacy in vitro, in vivo, and in clinical PJIs.…”