Unpredictable Effects of Rifampin as an Adjunctive Agent in Elimination of Rifampin-Susceptible and -Resistant Staphylococcus aureus Strains Grown in Biofilms

Abstract

The use of rifampin as an adjunct in biofilm-associated infections is based on the ability to penetrate into biofilms and a presumed activity against dormant bacteria. Yet, its efficacy remains contradictory, and rifampin-resistant strains frequently emerge during therapy. Therefore, the efficacy against rifampin-susceptible and isogenic rifampin-resistant methicillin-susceptible Staphylococcus aureus (MSSA) strains was evaluated. Biofilms were generated under static conditions using MSSA with various genetic backgrounds. Oxacillin alone or with rifampin at various concentrations was subsequently added, and after 24 h biomass and viable cell counts were determined. Upon rifampin addition, interstrain variations in viable count change, ranging from a tendency toward antagonism to synergy, were observed among all strains tested, irrespective of the genetic background of the strain. Similar variations were observed in changes in biomass. The decrease in viable count upon rifampin addition was negatively correlated to formation of large amounts of biomass, since strains embedded by more biomass showed a diminished reduction in viable count. Rifampin (1 g/ml) as adjunct to oxacillin achieved greater reductions in biomass produced by most rifampin-susceptible isolates, ranging from 17 to 54%, compared to 4% for oxacillin alone. In contrast, rifampin had no additional value in reduction of biomass of isogenic rifampin-resistant mutants. At subinhibitory concentrations of rifampin (0.008 g/ml), none of the strains tested yielded an extra reduction in biomass that was >40%. In conclusion, the effects of rifampin as adjunct on biomass and viable count were unpredictable, and the use of rifampin against biofilm containing rifampin-resistant strains seems unwarranted.

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

“…On the other hand, the role of RIF against R. equi biofilm is controversial. Our data agree fairly well with those of previous studies [41] and further support the use of RIF as an adjunct treatment in place of monotherapy.…”

The Use of Vacuum Dressings for Dead Space Management in Deep Surgical Site Infections Allows Implant and Bone Graft Retention

“…7 Adding rifampicin has been shown to increase the cure rate of infections caused by staphylococci, 11 though its efficacy has been found to be unpredictable in some studies. 12 , 13 It is also useful to synergistically potentiate antibiotic glycocalyx penetration when instrumentation is present. Duration of antibiotics is a contentious issue, but most studies support a treatment course of 6 weeks.…”

Poly(trimethylene carbonate) as a carrier for rifampicin and vancomycin to target therapy‐recalcitrant staphylococcal biofilms

“…Arguably, treating strains with antibiotic concentrations below their MIC value could cause resistance, which emerges rapidly especially with rifampicin, although the responsible resistance associated mutations are reported to reduce the overall biological fitness of S. aureus . Some researchers dissuade the addition of rifampicin in the treatment of rifampicin resistant S. aureus infections . However, rifampicin is reported to enhance the activity of vancomycin in biofilms, and even sub‐inhibitory concentrations of rifampicin are reported to inhibit cytotoxin production in S. aureus …”