Assessment of Bacteriophage Pharmacokinetic Parameters After Intra-Articular Delivery in a Rat Prosthetic Joint Infection Model
Prosthetic joint infections (PJIs) are a serious complication of orthopedic surgery. Bacteriophage (phage) therapy shows promise as an adjunctive treatment but requires further study, particularly in its pharmacokinetics. Consequently, we performed a pharmacokinetic assessment of phage therapy for P...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-11-01
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| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/16/11/1800 |
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| Summary: | Prosthetic joint infections (PJIs) are a serious complication of orthopedic surgery. Bacteriophage (phage) therapy shows promise as an adjunctive treatment but requires further study, particularly in its pharmacokinetics. Consequently, we performed a pharmacokinetic assessment of phage therapy for PJIs using a <i>Staphylococcus epidermidis</i> Kirschner wire-based prosthesis rat model. We used 52 male Sprague–Dawley rats in four groups: negative controls (no phage, sterile implant), PJI controls (bacteria, no phage), sterile phage (phages given, sterile implant), and PJI (bacteria, phages given). The PJI groups were inoculated with ~10<sup>6</sup> CFU of <i>S. epidermidis</i>. The groups receiving phage were intra-articularly injected with ~10<sup>8</sup> PFU of vB_SepM_Alex five days post-implantation. The rats were euthanized between 30 min and 48 h post-injection. The measured phage concentrations between the PJI rats and the sterile controls in periarticular tissues were not significantly different. In a noncompartmental pharmacokinetic analysis, the estimated phage half-lives were under 6 h (combined: 3.73 [IQR, 1.45, 10.07]). The maximum phage concentrations were reached within 2 h after administration (combined: 0.75 [0.50, 1.75]). The estimated phage mean residence time was approximately three hours (combined: 3.04 [1.44, 4.19]). Our study provides a preliminary set of pharmacokinetic parameters that can inform future phage dosing studies and animal models of phage therapy for PJIs. |
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| ISSN: | 1999-4915 |