This study evaluated the pharmacokinetics of commercial gentamicin-impregnated collagen sponges (GICS) applied subcutaneously in dogs. In six healthy beagles, an 11 ×6 cm subcutaneous pocket was created, a folded 10×10 cm GICS was inserted, and saline was injected to mimic a seroma. Wound fluid samples were aspirated, and the gentamicin concentration was determined. Simultaneously, blood samples were collected to evaluate the corresponding systemic gentamicin concentration. All samples were collected before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120, and 168 hours after GICS placement. The local C of gentamicin was reached after 0.5 hours (range, 0.5-1.0 hours) post-implantation in 5/6 dogs at a median concentration of 2053.3 µg/mL (range, 918.0-2791.9 µg/mL). Whitin 24 hours, the local concentration dropped below the MIC for Staphylococcus sp. (4 µg/mL) in 5/6 dogs. Plasma C was achieved at a median of 1.2 hours post-implantation (range, 1.0-2.0 hours) and reached a median concentration of 10.3 µg/mL (range, 8.8-18.03 µg/mL). After 6 hours, the gentamicin concentration in the plasma was below 4 µg/mL in all dogs. The GICS provided a high local concentration of gentamicin in a short time with a local Cmax:MIC ratio of 513:1, largely sufficient to eliminate susceptible bacteria, including methicillin-resistant Staphylococcus pseudintermedius (MRSP) and Pseudomonas sp., in a clinical setting. The repeated administration of saline in the present study seemed to have induced a quicker gentamicin release from the GICS than described in previous studies that typically dealt with "drier" wounds.
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http://dx.doi.org/10.1016/j.tvjl.2024.106201 | DOI Listing |
Carbohydr Res
January 2025
Department of Chemical Sciences, University of Naples Federico II, Naples, I-80126, Italy.
Herein we report the synthesis of a novel di-O-acylated DNJ derivative, conceived to study whether iminosugar derivatization with a lipophilic acyl moiety could positively affect its antibacterial properties. The well-known PS-TPP/I/ImH activating system was used to readily install the acyl chains on the iminosugar, leading to the desired compound in high yield. Biological assays revealed that a di-O-lauroyl DNJ derivative enhanced the antibacterial effect of gentamicin and amikacin against S.
View Article and Find Full Text PDFAntibiotics (Basel)
January 2025
Adelaide Medical School, Robinson Research Institute, The University of Adelaide, Adelaide 5005, Australia.
Effective gentamicin dosing is crucial to the survival of neonates with suspected sepsis but requires a careful balance between attaining both effective peak and safe trough concentrations. We aimed to systematically compare existing gentamicin dosing guidelines for neonates in Australia to determine the extent to which they reach therapeutic targets. Simulations of a single gentamicin dose to a virtual representative neonatal population according to each Australian guideline were performed using population pharmacokinetic modelling.
View Article and Find Full Text PDFAntibiotics (Basel)
January 2025
Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan.
: is a leading cause of infective endocarditis (IE), which causes diverse clinical symptoms and even death. Recurrence after treatment is a crucial problem in IE, possibly caused by the presence of "persister" cells, a small bacterial population that can survive antimicrobials. In this study, the residual risk for penicillin G (PCG) and gentamicin (GM), used for treating IE, to induce persisters, was investigated.
View Article and Find Full Text PDFJ Bone Joint Surg Am
January 2025
Harris Orthopaedics Laboratory, Massachusetts General Hospital, Boston, Massachusetts.
Background: Periprosthetic joint infections (PJIs) are a major complication of total joint replacement surgeries. This study investigated the enhancement of mechanical properties and antibiotic release in ultra-high molecular weight polyethylene (UHMWPE) through the encapsulation of submicron gentamicin sulfate (GS) particles, addressing the critical need for improved implant materials in orthopaedic surgery, particularly in managing PJIs.
Methods: The present study involved embedding submicron GS particles into UHMWPE flakes at concentrations of 2% to 10% by weight.
PLoS Biol
January 2025
Microbial Molecular Evolution Group, Department of Microbial Population Biology, Max Planck Institute for Evolutionary Biology, Plön, Germany.
Bacteriophages infect gram-negative bacteria by attaching to molecules present on the bacterial surface, often lipopolysaccharides (LPS). Modification of LPS can lead to resistance to phage infection. In addition, LPS modifications can impact antibiotic susceptibility, allowing for phage-antibiotic synergism.
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