Efficacy of Linezolid and Fosfomycin in Catheter-Related Biofilm Infection Caused by Methicillin-ResistantStaphylococcus aureus

Abstract

As long-standing clinical problems, catheter-related infections and other chronic biofilm infections are more difficult to treat due to the high antibiotic resistance of biofilm. Therefore, new treatments are needed for more effective bacteria clearance. In this study, we evaluated the antibacterial activities of several common antibiotics alone and their combinations against biofilm-embedded methicillin-resistant staphylococcus aureus (MRSA) infections, both in vitro and in vivo. In brief, fosfomycin, levofloxacin, and rifampin alone or in combination with linezolid were tested in vitro against planktonic and biofilm-embedded MRSA infection in three MRSA stains. The synergistic effects between linezolid and the other three antibiotics were assessed by fractional inhibitory concentration index (FICI) and time-kill curves, where the combination of linezolid plus fosfomycin showed the best synergistic effect in all strains. For further evaluation in vivo, we applied the combination of linezolid and fosfomycin in a catheter-related biofilm rat model and found that viable bacteria counts in biofilm were significantly reduced after treatment (P < 0.05). In summary, we have shown here that the combination of linezolid and fosfomycin treatment had improved therapeutic effects on biofilm-embedded MRSA infection both in vitro and in vivo, which provided important basis for new clinical therapy development.

In vitro activity and post-antibiotic effects of linezolid in combination with fosfomycin against clinical isolates of <em>Staphylococcus aureus</em>

“…Sahuquillo Arce et al reported FICI values ranging from 0.375 to 0.75 for linezolid-fosfomycin combination displayed synergistic effect against 80% tested strains, 20 while Chai et al obtained FICI values of 0.375–0.5 with the same combination for S. aureus . 7 In our study, synergistic results were observed for all strains except No.24, 14, and 55 strains with FICI values ranging from 0.375 to 0.75. We hypothesized that the no synergistic strains (No.24, 14, and 55) may be attributable to difference among bacterial species and strains.…”

“…Several previous studies have evaluated the potential for synergy between linezolid and fosfomycin in vitro and in vivo. 7 – 9 However, further investigation is necessary to support the use of this combination because of very limited number of trials. In addition, the optimal regimen of the combination therapy has also been rarely studied.…”

Pharmacodynamics of linezolid-plus-fosfomycin against vancomycin-susceptible and -resistant enterococci in vitro and in vivo of a Galleria mellonella larval infection model

“…Tang et al reported that teicoplanin combined with fosfomycin revealed excellent synergistic activity against VRE (24). Previous studies have confirmed the potent synergism of the combination of linezolid and fosfomycin against another common multidrug-resistant gram-positive pathogen, methicillin-resistant staphylococcus aureus (MRSA) (25). However, reports in regard to this combination therapy when used against VRE are scarce.…”

“…The combination treatment at 1×MIC showed a synergistic effect against No.1 and No.2, and also displayed an additive activity against ATCC29212 and No.4. The synergism of the linezolid plus fosfomycin was described in several studies, especially against MRSA (25, 30). Based on my research, only one study was found that explored the effectiveness of linezolid combined with fosfomycin against VRE in vitro via time-kill curve experimentation and similar results were detected in that study (31).…”

Diabetes With Osteomyelitis in Rare Sites With Sepsis as the First Diagnosis: Three Case Reports and Literature Review

“…Although rifampicin cannot be used alone to treat osteomyelitis, it can improve the cure rate when added to various other antibiotics [19]. In addition, fusidic acid [20] and fosfomycin [21] are suitable adjuvant drugs for combination therapy.…”