Evaluation of Staphylococcal Bacteriophage Sb-1 as an Adjunctive Agent to Antibiotics Against Rifampin-Resistant Staphylococcus aureus Biofilms

Abstract

Rifampin plays a crucial role in the treatment of staphylococcal implant-associated infection, as it is the only antibiotic capable of eradicating Staphylococcus aureus biofilms. However, the emergence of rifampin resistance strongly limits its use. Combinatorial therapy of antibiotics and bacteriophages may represent a strategy to overcome the resistance. Here, we evaluated the activity of staphylococcal bacteriophage Sb-1 in combination with different antibiotics against the biofilms of 10 rifampin-resistant S. aureus clinical strains, including MRSA and MSSA. S. aureus biofilms formed on porous glass beads were exposed to antibiotics alone or combined with Sb-1 simultaneously or staggered (first Sb-1 for 24 h followed by antibiotic). Recovered bacteria were detected by measuring growth-related heat production at 37°C (isothermal microcalorimetry) and the biofilm eradication was assessed by sonication of beads and plating of the resulting sonication fluid. Minimum biofilm eradication concentration (MBEC) was defined as the lowest concentration of antibiotic required to kill all adherent bacteria, resulting in absence of growth after plating the sonication fluid. Tested antibiotics presented high MBEC values when administered alone (64 to > 1,024 μg/ml). The simultaneous or staggered combination of Sb-1 with daptomycin showed the highest activity against all MRSA biofilms, whereas the exposure to Sb-1 with vancomycin showed no improved anti-biofilm activity. Staggered administration of Sb-1 and flucloxacillin, cefazolin, or fosfomycin improved the antibiofilm activity in four out of six MSSA, whereas simultaneous exposure exhibited similar or lesser synergy. In conclusion, the combinatorial effect of Sb-1 and antibiotics enabled to eradicate rifampin-resistant S. aureus biofilms in vitro .

A Case of In Situ Phage Therapy against Staphylococcus aureus in a Bone Allograft Polymicrobial Biofilm Infection: Outcomes and Phage-Antibiotic Interactions

“…More recently, a literature review presented numerous occurrences of preclinical studies documenting rifampin's inhibitory effects on phage infectivity [21]. Yet, evidence suggests that the possibility of phage-rifampin synergy should not be ruled out in specific conditions, for example through combined use of rifampin and phage Sb-1, another representative of genus Kayvirus, in rifampin-susceptible S. aureus biofilms [22].…”

Synergy between Phage Sb-1 and Oxacillin against Methicillin-Resistant Staphylococcus aureus

“…Furthermore, the development of phage resistance by modifying multi-drug efflux pump activity can increase the sensitivity to antibiotics [6]. A number of studies have already addressed the potential impact of a dual approach against S. aureus using a lytic phage in combination with MRSA-effective antibiotics, such as rifampicin, linezolid, fosfomycin, daptomycin, and vancomycin [7][8][9][10][11][12][13], as well as in combination with aminoglycosides, quinolone antibiotics, and β-lactam antibiotics [5,[11][12][13]. Interestingly, synergistic interactions between a phage and an antibiotic can also be observed in cases in which the pathogen is resistant against the antibiotic [14,15].…”

Effect of Phage SAvB14 combined with antibiotics on Staphylococcus aureus variant bovis

“…Research has (Wang et al, 2020) experimentally confirmed that staggered introduction of Sb-1, flucloxacillin, cefazolin or fosfomycin improved antibiotic activity toward biofilms in four of six methicillin-sensitive S. aureus, whereas simultaneous influence demonstrated similar or less synergy. Our studies correlate with the earlier published data (Wang et al, 2020), when staggered introduction of phage and antibiotic caused 97.5-100.0% destruction of biofilm.…”

“…However, when biofilms are first exposed to actions of antibiotics and then phages, the population of bacteria that the phage could infect decreases, which may negatively affect kinetics of bacteriophage reproduction and ultimately the efficiency of phage therapy (Horiuk et al, 2020;Morrisette et al, 2020). Research has (Wang et al, 2020) experimentally confirmed that staggered introduction of Sb-1, flucloxacillin, cefazolin or fosfomycin improved antibiotic activity toward biofilms in four of six methicillin-sensitive S. aureus, whereas simultaneous influence demonstrated similar or less synergy. Our studies correlate with the earlier published data (Wang et al, 2020), when staggered introduction of phage and antibiotic caused 97.5-100.0% destruction of biofilm.…”