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This in vitro study investigated the efficacy of two phages (SaMD07FSphi1 and SaNSI1469phi1), alone and in combination with vancomycin, against Staphylococcus aureus and Staphylococcus epidermidis biofilms grown on stainless steel Kirschner wires, using 8 PJI isolates. The combination of phage SaMD07FSphi1 and vancomycin showed significant log reduction factors (LRFs) at 24 hours for some S. aureus isolates, while phage SaNSI1469phi1 plus vancomycin showed similar results for some S. epidermidis and S. aureus isolates. Increased activity was observed at 6 hours in some cases, with bacterial regrowth at 24 hours.
Phage therapy, particularly in combination with vancomycin, demonstrates potential in vitro activity against staphylococcal biofilms associated with PJI, although regrowth at 24 hours suggests limitations.
Abstract Background Staphylococci are the most frequent microorganisms in periprosthetic joint infection (PJI) and treatment remains challenging. Phage is being considered as a potential treatment. Here, the in vitro activity of phages SaMD07FSphi1or SaNSI1469phi1, alone and in combination with vancomycin against staphylococcal biofilms was evaluated. Figure 1 In vitro activity of phage SaMD07FSphi1 against S. aureus and S. epidermidis biofilms Figure 2 In vitro activity of phage SaNSI1469phi1 against S. aureus and S. epidermidis biofilms Methods Biofilms were grown at 37°C on 4 cm stainless steel K-wires in tryptic soy broth (TSB) with 106 cfu/ml of S. epidermidis or S. aureus (8 PJI isolates with phage activity against planktonically-grown bacteria). After 24 h, 3 K-wires were quantitatively cultured to define pre-treatment bacterial loads, with the remaining assigned to one of four treatment groups: TSB, phage (4 x 106 plaque forming units/ml), vancomycin (16 µg/ml) or phage/vancomycin. K-wires were incubated for 6 or 24 h at 37°C, rinsed, sonicated, and quantitatively cultured. Testing was performed in triplicate and on 3 separate days and mean log10 cfu/K-wire reduction factors (LRFs) versus TSB calculated. Results Phage SaMD07FSphi1 (Figure 1) plus vancomycin showed LRFs of 2.8 (p, 0.0003) and 2.3 (p, 0.0177) log10 cfu/K-wire at 24 h for S. aureus IDRL-6121 and S. aureus IDRL-8454, respectively, whereas phage alone showed was 3.1 (p, 0.0003) and 3.0 (p, 0.0003), respectively. All treatments were ≤1.0 log10 cfu/K-wire 24 h LRFs for S. aureus IDRL-6175, S. epidermidis IDRL-5966 and S. epidermidis IDRL-6108.This phage plus vancomycin showed LRFs of 0.6 log10 cfu/K-wire at 6 h for S. epidermidis IDRL-5966 and S. aureus IDRL-6175, with bacterial regrowth at 24 h. Phage SaNSI1469phi1 (Figure 2) plus vancomycin showed 24 h LRFs of 2.0 (p, 0.02) and 3.2 (p, 0.003) log10 cfu/K-wire for S. epidermidis IDRL-6955 and S. aureus IDRL-7299, respectively, whereas phage alone was 0.2 (p, 0.17) and 0.5 (p, 0.03) log10 cfu/K-wire, respectively. All treatments showed ≤1.0 log10 cfu/K-wire 24-hour LRFs log10 cfu/K-wire for S. epidermidis IDRL-10273. This phage alone showed 6 h LRFs of 1.0 and 1.3 for S. epidermidis IDRL-6955 and S. aureus IDRL-7299, with bacterial regrowth at 24 h. Conclusion Phages SaMD07FSphi1 and SaNSI1469phi1 alone and with vancomycin showed activity against staphylococcal biofilms formed by 4 isolates. Increased activity was observed at 6 h in some cases, with bacterial regrowth at 24 h. Disclosures Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication, a patent on PET imaging of bacterial infection: a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication, a patent on PET imaging of bacterial infection|MicuRx Pharmaceuticals and bioMérieux: Grant/Research Support|PhAST, Day Zero Diagnostics, DEEPULL DIAGNOSTICS, S.L., Nostics, HealthTrackRx, bioMérieux and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course: Honoraria
