Salphage: Salvage Bacteriophage Therapy for Recalcitrant MRSA Prosthetic Joint Infection

Abstract

Prosthetic joint infections are a devastating complication of joint replacement surgery. Consequently, novel therapeutics are needed to thwart the significant morbidity and enormous financial ramifications that are associated with conventional treatments. One such promising adjuvant therapeutic is bacteriophage therapy given its antibiofilm activity and its ability to self-replicate. Herein we discuss the case of a 70-year-old female who had a recalcitrant MRSA prosthetic knee and femoral lateral plate infection who was successfully treated with adjuvant bacteriophage therapy. Moreover, this case discusses the importance of propagating bacteriophage therapeutics on bacteria that are devoid of toxins and the need to ensure bacteriophage activity to all bacterial morphologies. Overall, this case reinforces the potential benefit of using personalized bacteriophage therapy for recalcitrant prosthetic joint infections, but more translational research is needed to thereby devise effective, reproducible clinical trials.

Phage therapy in prosthetic joint infections caused by Staphylococcus aureus – A literature review

“…Doub et al. reported results from a treatment of a prolonged MRSA prosthetic knee infection with the phage Mallokai [ 53 ]. The authors pointed out that a testing of the phage prior to therapeutic application indicated the absence of endotoxins.…”

“…Growth inhibition assays confirmed the lytic killing by the same phage as independent of the particular morphology. Still, it is highlighted that the possibility of multiple colony morphologies should be met with the verification of broad enough efficacy of the phages [ 53 ].…”

“…Notably, the reviewed case reports had one aspect convincingly in common: The initial clinical condition of the patient following standard therapeutic schemes resembled a dead end and phage therapy, as shown by clinical success, proved to be rather a salvage therapy [ 48 – 54 ]. In some cases, even amputation was originally taken into consideration, but could be principally avoided through compassionate or emergency use of phage therapy after a second opinion was obtained [ 48 , 50 , 52 ].…”

“…In some cases, even amputation was originally taken into consideration, but could be principally avoided through compassionate or emergency use of phage therapy after a second opinion was obtained [ 48 , 50 , 52 ]. Complicating the matter, the patients occasionally had a variety of pre-existing conditions including diabetes, hyperlipidemia, hypertension, or lymphedema [ 51 – 54 ]. Finally, just as a personalized approach was generally adopted [ 49 , 53 , 54 ], phage therapy was found to be safe also as a magistral preparation originating in a research and development laboratory instead of a good manufacturing practice laboratory [ 51 ].…”

Isolation and in vitro characterization of novel S. epidermidis phages for therapeutic applications

“…Therapeutic potential of phages in the long-term largely depends on their activity against clinically relevant strains. Staphylococcus phages have already reached the level of clinical trials and are being used to treat infections in the context of expanded use, demonstrating their therapeutic potential and efforts to further develop this field ( Lehman et al., 2019 ; Doub et al., 2020 ; Ferry et al., 2020 ; Van Nieuwenhuyse et al., 2021 ; Doub et al., 2022 ). Phages isolated in this study, COP-80A, COP-80B, and COP-110, infect the majority of S. epidermidis strains tested and also other coagulase-negative strains from our collection, similar as observed for phages phiIPLA-C1C and SEP1 ( Melo et al., 2014 ; Gutiérrez et al., 2015 ).…”