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Lipid-based slow-release formulation of amikacin sulfate reduces foreign body-associated infections in mice
A A Roehrborn1, J F Hansbrough, B Gualdoni
1DepoTech Corporation, La Jolla, California, USA.
Abstract:
Treatment and prophylaxis of uncomplicated infections with standard systemic antibiotics are usually successful. However, standard systemic antibiotic therapy alone is frequently unsatisfactory in certain circumstances, such as the presence of a foreign body (FB), necrotic tissue, overwhelming bacterial inoculum, or poor vascular supply to the involved tissues. We have developed a lipid-based sustained release formulation of amikacin sulfate (DepoFoam encapsulated amikacin sulfate [DEAS]) as a biodegradable, locally injectable antibiotic for such circumstances. The encapsulated drug is released over 7 to 10 days. We tested the efficacy of this formulation in an FB infection model in which Teflon tubes (length, 1 cm; outside diameter, 1.6 mm) were implanted into the subcutaneous tissue in mice and the local site was inoculated with 0.87 x 10(7) CFU of Staphylococcus aureus 3 days later. Inoculation was followed by either no treatment or a local injection of DEAS, free amikacin sulfate, non-drug-containing DepoFoam, or systemic free amikacin sulfate. All drug applications contained 1 mg of amikacin. One group was implanted with the FB and left unchallenged with bacteria and untreated as a sterile control group. All animals were sacrificed 10 days following FB implantation. FBs were retrieved from tissues by an aseptic technique and incubated in liquid culture media for 7 days. Local wound tissue was excised and processed to determine the number of CFU per gram of tissue. Treatment with local or systemic free amikacin had no effect on the number of infected FBs or on the log CFU in wound tissue compared with the untreated or non-drug-containing DepoFoam group. Compared with local free amikacin therapy, the number of infected FBs was reduced from 86 to 25% (P=0.02) following treatment with DEAS, and log CFU per gram of tissue was significantly decreased from 4.8 +/- 0.9 to 1.3 +/- 0.6 (P<0.0005). DEAS may have clinical utility as locally injected antibiotic in certain infections.
Insights
A novel sustained-release amikacin sulfate formulation (DEAS) effectively treated Staphylococcus aureus foreign body infections in mice. This injectable antibiotic significantly reduced bacterial load and infected foreign bodies compared to standard treatments.
Area of Science:
- Pharmacology
- Biomedical Engineering
- Infectious Diseases
Background:
- Standard antibiotic therapy is often insufficient for infections involving foreign bodies, necrotic tissue, or poor vascular supply.
- Developing localized, sustained-release antibiotic delivery systems is crucial for overcoming these challenges.
- Amikacin sulfate is a potent aminoglycoside antibiotic with activity against Gram-negative and Gram-positive bacteria.
Purpose of the Study:
- To evaluate the efficacy of a lipid-based sustained-release formulation of amikacin sulfate (DepoFoam encapsulated amikacin sulfate [DEAS]) for treating foreign body infections.
- To compare the effectiveness of DEAS with free amikacin sulfate (local and systemic) and a non-drug-containing control in a mouse model.
Main Methods:
- A foreign body infection model was established in mice using Teflon tubes implanted subcutaneously and inoculated with Staphylococcus aureus.
- Mice were treated with locally injected DEAS, free amikacin sulfate, non-drug-containing DepoFoam, or systemically administered free amikacin sulfate.
- Efficacy was assessed by quantifying the percentage of infected foreign bodies and the bacterial load (CFU per gram of tissue) in the wound.
Main Results:
- Local or systemic free amikacin sulfate showed no significant effect on infection rates or bacterial load compared to untreated controls.
- DEAS treatment significantly reduced the percentage of infected foreign bodies from 86% to 25% (P=0.02).
- DEAS markedly decreased bacterial load in wound tissue from log CFU 4.8 ± 0.9 to 1.3 ± 0.6 (P<0.0005).
Conclusions:
- DepoFoam encapsulated amikacin sulfate (DEAS) demonstrates significant efficacy in treating challenging Staphylococcus aureus foreign body infections.
- Sustained local delivery of amikacin sulfate via DEAS offers a promising therapeutic strategy for infections where conventional antibiotics fail.
- DEAS warrants further investigation for potential clinical applications in managing complex localized infections.