Antibiotic Selection for Sustained Local Therapy May Be Important to Reduce Pseudomonas aeruginosa Dominance Against Staphylococcus aureus and Bone Response Modulation in an Ovine Polymicrobial Fracture-Related Infection Model
Abstract
Polymicrobial fracture-related infections (FRIs) underpinned by bacterial biofilms pose therapeutic challenges distinct from those of monomicrobial infection, as interspecies dynamics may alter both antimicrobial response and host tissue injury. This study evaluated systemic and local antibiotic strategies in an ovine FRI model co-inoculated with a polymicrobial Staphylococcus aureus and Pseudomonas aeruginosa biofilm. At 21 days, untreated positive controls retained substantial total bioburden yet paradoxically preserved bone volume and exhibited low osteoclast activity, contrasting with the marked osteolysis previously observed in monomicrobial infection controls using this model. Although untreated controls remained S. aureus predominant, their S. aureus:P. aeruginosa ratio declined from approximately 200:1 at inoculation to 15:1, indicating a progressive ecological shift over time. A systemic levofloxacin plus rifampin regimen more effectively reduced S. aureus than P. aeruginosa. Likewise, all antibiotic-treated groups shifted from an S. aureus-dominant inoculum toward P. aeruginosa predominance, consistent with unequal antimicrobial suppression altering polymicrobial pathogen balance. Single-dose local antibiotic powder and calcium sulfate bead strategies provided inconsistent microbiological benefit and failed to preserve bone. Reloadable local antibiotic delivery reduced S. aureus tissue bioburden and preserved the greatest bone volume among antibiotic-treated groups…
Read the paper
Related studies
- Ferulic acid regulates the AKT/GSK-3β/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model
- Novel Pharmacokinetic/Pharmacodynamic Parameters Quantify the Exposure–Effect Relationship of Levofloxacin against Fluoroquinolone-Resistant Escherichia coli
- Photochemical behavior of levofloxacin
- Correlation Between Dissolution Profiles of Salt-Form Drugs in Biorelevant Bicarbonate Buffer and Oral Drug Absorption: Importance of Dose/ Fluid Volume Ratio
- Evaluation of the synergistic potential and mechanisms of action for de novo designed cationic antimicrobial peptides
- Synthesis of [11C]levofloxacin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.