Dynamic PET-facilitated modeling and high-dose rifampin regimens for Staphylococcus aureus orthopedic implant–associated infections

Abstract

Current rifampin dosing achieves subtherapeutic concentrations within S. aureus –infected bone, which can be overcome with higher rifampin dosing.

Antibiotic‐Derived Radiotracers for Positron Emission Tomography: Nuclear or “Unclear” Infection Imaging?

“…For instance, from the series of PK/PD studies using [ 11 C]RIF, the multi‐compartmental (lungs, brain and bone) quantification of spatially heterogeneous and highly variable tracer exposure to multiple distinct lesions within an individual patient was possible. So far, and considered as uncharted territory, the image‐guided analysis revealed the presence of multiple, but variable, pathophysiological responses unique to each lesion that can affect drug bioavailability [71, 81–83] . It is known that inappropriate levels of antibiotic bioavailability and pathogen exposure can lead to treatment failure and the selection of resistant organisms.…”

“… [48] Later, a series of subsequent reports described in detail the spatial–temporal evolution of [ 11 C]RIF exposure to diverse TB lesions manifested within a panel of small animal models and human patients. [ 71 , 80 , 81 , 82 , 83 ] The piperazine moiety of rifampin was radiolabeled with [ 11 C]CH 3 I within 10 minutes in a reaction solution consisting of potassium carbonate dissolved in DMSO and MeCN and heated to 110 °C. [ 11 C]RIF product was subsequently purified via reverse‐phase HPLC and the acquired product fractions were concentrated in vacuo after the addition of ascorbic acid (to prevent oxidation).…”

Peptide–Polymer Conjugates: A Promising Therapeutic Solution for Drug-Resistant Bacteria

“…Whether natural and synthetic polymers, and whether they degraded or not, the high risks of microbial growth on the implanted devices are a common and serious problem in orthopedic surgery [134,135]. The formation of bac-terial biofilms at the interface between implants and tissues may cause persistent infection, so antibacterial treatment of implants is required [136].…”

Antibiotic‐Derived Radiotracers for Positron Emission Tomography: Nuclear or “Unclear” Infection Imaging?

“…So far, and considered as uncharted territory, the image-guided analysis revealed the presence of multiple, but variable, pathophysiological responses unique to each lesion that can affect drug bioavailability. [71,[81][82][83] It is known that inappropriate levels of antibiotic bioavailability and pathogen exposure can lead to treatment failure and the selection of resistant organisms. Thus, more detailed pharmacologic drug characterization may have significant implications in future treatment optimization efforts.…”

“…reported the first successful radiosynthesis of [ 11 C]rifampin ([ 11 C]RIF) and used PET imaging to study its pharmacokinetic parameters in healthy non‐human primates [48] . Later, a series of subsequent reports described in detail the spatial–temporal evolution of [ 11 C]RIF exposure to diverse TB lesions manifested within a panel of small animal models and human patients [71, 80–83] . The piperazine moiety of rifampin was radiolabeled with [ 11 C]CH 3 I within 10 minutes in a reaction solution consisting of potassium carbonate dissolved in DMSO and MeCN and heated to 110 °C.…”