Elution Of Gentamicin Research Articles

Liquid dextran does not increase the elution rate of different antibiotics from bone cement

To investigate the possibility of increasing elution of fosfomycin, gentamicin, clindamycin, and vancomycin by the addition of dextran fluid during the cement-mixing phase. In 12 test series, we produced standardized, antibiotic-loaded test specimens of cement, with and without addition of dextran, and determined their effectiveness against three reference pathogens in agar diffusion and elution tests. In the test series using combined agents, Refobacin(®)-Palacos(®)R plus fosfomycin continuously produced the largest zone of inhibition, both against methicillin-sensitive Staphylococcus aureus (p = 0.009) and against methicillin-resistant Staphylococcus aureus (p = 0.009). The addition of dextran to the various test series had no useful effect on the size of the zone of inhibition for any of the antibiotics tested. Dextran supplementation in Refobacin(®)-Palacos(®)R bone cement did not have the hope for positive effect on the elution rate of bound antibiotics.

In Vitro Elution Characteristics of Gentamicin and Vancomycin from Synthetic Bone Graft Substitutes

Objects:Beta tricalciumphosphate pellets loaded with individualized antibiotics may represent novel options in the treatment of osteomyelitis and infectious bone disease. Here, the in vitro antibiotic elution of vancomycin and gentamicin from the synthetic bone graft substitutes Cerasorb® and Cerasorb M® was tested. Methods:Antibiotic elution and concentration of gentamcin and vancomycin were measured using photometrically-based measurement and homogeneous particle-enhanced turbidimetric inhibition immunoassays (PETINIA). Results:Initially both materials showed a high release of the loaded antibiotics, with Cerasorb M® showing lower release levels for gentamicin and vancomycin than Cerasorb®. Gentamicin concentrations of Cerasorb M granules and Cerasorb were below the minimum detectiontreshold until day four and six of the experiment respectively. The vancomycin release-level followed a similar pattern, although the vancomycin concentration eluted by Cerasorb M® granules stayed above the detection threshold during the experimental time.Conclusions: Cerasorb® and Cersorb M® may represent a new treatment option in osteomyelitis and infectious bone disease.

Characterisation of in vivo release of gentamicin from polymethyl methacrylate cement using a novel method

The purpose of this study was to investigate the in vivo elution kinetics of gentamicin from bone cement by assessing antibiotic levels in the urine. Urinary samples of 35 patients who had undergone primary total hip arthroplasty were collected post-operatively. Gentamicin concentrations were analysed using the fluorescence polarisation immunoassay technique. The mean duration of urinary gentamicin release in all cases was 43 days (range 13-95). There was still detectable gentamicin at the final collection in 20% (7/35) of cases, and in these cases, the mean gentamicin release was 71 days. From the assessment of urinary gentamicin, we were able to demonstrate the biphasic gentamicin elution from bone cement. In addition, there were detectable concentrations of the antibiotic from the urinary samples for prolonged periods of up to two to six months. Our study indicates that the assessment of urinary antibiotics can offer a non-invasive method of monitoring the in vivo release kinetics of antibiotics from bone cement.

In vitro elution and dissolution of tobramycin and gentamicin from calcium phosphate

This study was conducted to investigate the in vitro drug release characteristics of tobramycin and gentamicin from calcium phosphate. Calcium phosphate beads were loaded with tobramycin and gentamicin separately to form 2 types of antibiotic beads to generate antibiotic drug delivery system for the treatment of osteomyelitis. Tobramycin and gentamicin concentrations were determined spectrophotometrically by measuring the absorbance at 400 nm. The standard graphs for tobramycin and gentamicin concentration versus absorbance reading were prepared as references to identify the concentration of the drugs release after incorporating calcium phosphate over 8 weeks. This study showed that incorporating tobramycin and gentamicin with calcium phosphate provided slow residual release of antibiotic from 30 min to 1344 h (8 weeks) and dissolution of calcium phosphate. In this respect, the drug delivery systems of tobramycin and gentamicin-incorporated calcium phosphate have potential of controlling drug release.

Elution of gentamicin and vancomycin from polymethylmethacrylate beads and hip spacers in vivo

Background and purpose Late infections after total hip arthroplasty are still a problem. Treatment procedures include resection arthroplasty with implantation of antibiotic-loaded beads or implantation of an antibiotic-impreganted spacer. However, little is known about antibiotic elution from bone cement beyond the first 2–3 postoperative days in humans.Methods 17 hip spacers (80g PMMA, 1g gentamicin, and 4 g vancomycin) and 11 chains (40 g PMMA, 0.5 g gentamicin, and 2 g vancomycin) in 28 patients were studied. The release of both agents was measured in the drainage fluid on a daily basis. The drains were left in situ until less than 50 mL was produced per day. The elution of both antibiotics was determined by fluorescence polarization immunoassay. Systemic antibiotics were given postoperatively according to antibiogram. If possible, no gentamicin or vancomycin was given.Results Peak mean concentrations from beads and spacers were reached for gentamicin (1,160 (12–371) µg/mL and 21 (0.7–39) µg/mL, respectively) and for vancomycin (80 (21–198) µg/mL and 37 (3.3–72) µg/mL) on day 1. The last concentrations to be determined were 3.7 µg/mL gentamicin and 23 µg/mL vancomycin in the beads group after 13 days, and 1.9 µg/mL gentamicin and 6.6 µg/mL vancomycin in the spacer group after 7 days. Between the fifth and seventh day, an intermittent increase in elution of vancomycin from both beads and spacers and of gentamicin from spacers was noticed. No renal or hepatic dysfunction was observed.Interpretation Beads showed higher elution characteristics in vivo than the spacers due to their larger surface area; however, a great amount of inter-subject variability was seen for both beads and spacers. The inferior elution properties of spacers emphasize the importance of additional systemic antibiotics for this treatment procedure during the postoperative period. Future studies should clarify whether the dose of antibiotics or length of antibiotic therapy may be reduced in the case of bead implantation, without jeopardizing the control of infection.

Optimized Elution of Daptomycin from Polymethylmethacrylate Beads

We demonstrate that xylitol can be added to polymethylmethacrylate (PMMA) bone cement to enhance the elution of daptomycin in terms of both the peak and sustained release of antibiotic. We also demonstrate that a PMMA-xylitol formulation optimized for daptomycin can be used to enhance the elution of both vancomycin and gentamicin.

Liquid Gentamicin and Vancomycin in Bone Cement: A Potentially More Cost-Effective Regimen

This study investigated the use of liquid gentamicin, a much less costly antibiotic (<1/20 the price of tobramycin) with a broad antimicrobial spectrum, alone and in combination with vancomycin in bone cement. Standardized cement specimens loaded with 480 mg of liquid gentamicin, 4 g of powdered vancomycin, or both antibiotics were tested for elution characteristics, bioactivity, compressive strength, and porosity. Vancomycin elution was enhanced by 146% with the addition of gentamicin liquid, and gentamicin elution was enhanced by 45% when combined with vancomycin. Bioassay confirmed the bactericidal activity of the released antibiotics. Adding liquid gentamicin increased porosity, whereas adding vancomycin did not. Compressive strength decreased by 13%, 37%, and 45% in specimens containing vancomycin, liquid gentamicin, and both antibiotics, respectively. Despite inferior mechanical properties, the temporary nature of cement beads and spacers makes the liquid gentamicin–vancomycin mixture a potentially more cost-effective regimen in bone cement to treat musculoskeletal infections.

In vitro comparison of Refobacin-Palacos R with Refobacin Bone Cement and Palacos R + G

Background Refobacin Palacos R (RPR) is no longer produced and Palacos R + G (PRG) and Refobacin Bone Cement R (RBC) have been introduced to supersede it. We performed an in vitro study to ascertain whether the handling and mechanical properties of the more recent cement preparations are different to those of their predecessor.Methods The 3 cements were tested to ISO 5833 and German DIN 53435 standards. In addition, their gentamicin elution, shrinkage, viscosity, and handling characteristics were studied.Results All 3 cements had comparable mechanical properties exceeding the ISO 5833 and DIN 53435 standards. They eluted similar amounts of gentamicin and had comparable shrinkage. In the batches tested, RBC showed statistically significantly longer handling curves. Both PRG and RBC had statistically significantly lower viscosities as they cured compared to their predecessor.Interpretation Surgeons must be aware that both successor cements do not appear to have handling curves and viscoelastic properties identical to those of RPR.

In Vivo and In Vitro Studies of Antibiotic Release from and Bacterial Growth Inhibition by Antibiotic-Impregnated Polymethylmethacrylate Hip Spacers

The antimicrobial properties and the elution characteristics of gentamicin-vancomycin-loaded hip spacers were studied in vivo and in vitro. Vancomycin elution was greater than gentamicin elution. The antibiotic concentrations in vivo were less than those in vitro. Not dependent on implantation duration, growth inhibition by spacers in vitro was observed for 2 weeks. The reason for protracted wound healing cannot be insufficient antibiotic release.

The Effect of Glycine Filler on the Elution Rate of Gentamicin from Acrylic Bone Cement

Elution of antibiotics from acrylic bone cement (polymethylmethacrylate [PMMA]) is dependent on the access of fluid to the depths of the cement that contains the antibiotic. Commercially prepared antibiotic beads that are porous have higher elution rates than hand-mixed, nonporous antibiotic PMMA mixtures. To increase the elution of gentamicin from hand-mixed PMMA, glycine was added as a filler to produce porosity. Elution of gentamicin from the antibiotic PMMA-glycine mixture increased with increasing amounts of glycine. With 3.6 g gentamicin powder and 14 g of crystalline glycine per batch of Palacos PMMA, the elution of gentamicin from the PMMA at 2 days was, similar to the previously documented elution of gentamicin from commercially prepared porous Septopal PMMA beads. With further investigation it may be possible to identify a specific filler and a volume of filler that can be hand mixed in antibiotic PMMA to produce the elution behavior that is needed for specific clinical requirements.

Nanocrystalline hydroxyapatite and calcium sulphate as biodegradable composite carrier material for local delivery of antibiotics in bone infections

The use of polymethylmetacrylate beads for local delivery of antibiotics requires a second surgical procedure for their removal and resorbable calcium sulphate exhibits cytotoxic effects. In this work, a bioresorbable composite of calcium sulphate and nanoparticulate hydroxyapatite (PerOssal®) was studied regarding its antibiotic release properties and biocompatibility.Material characteristics of plain PerOssal® and pure calcium sulphate pellets were studied using scanning and electron microscopy and X-ray methods. Pellets were soaked with gentamicin and vancomycin, respectively. Release properties of both antibiotics from both materials were investigated over 10 days. Quantitative and qualitative cytotoxic assays were performed for biocompatibility testing.Specific surface was 106m2/g for PerOssal® and 2.2m2/g for pure calcium sulphate. Almost complete elution of gentamicin was found for both carrier materials (94.7% for PerOssal® vs. 95.8% for calcium sulphate) within 10 days, whereas vancomycin release was higher for PerOssal® (96.3% vs. 74.8%). PerOssal® showed higher initial and lower release after approximately 5 days compared to calcium sulphate. No significant in vitro cytotoxic differences were found between PerOssal® and nontoxic cell culture medium. Calcium sulphate showed cytotoxic effects in two out of four tests. PerOssal® exhibits excellent properties regarding resorption, biocompatibility, and antibiotic release.

Gentamicin release from two-solution and powder-liquid poly(methyl methacrylate)-based bone cements by using novel pH method.

The release of gentamicin as a function of time was measured for Palacos and two-solution bone cements by using a novel pH technique. The pH of an aqueous solution of gentamicin is a function of the gentamicin concentration and it decreases linearly over concentrations of 0.0-0.1 wt %. Therefore, a new, direct, and inexpensive in vitro technique was developed based on continuous readings of the pH in phosphate-buffered saline (PBS) at 37 degrees C to determine the release kinetics of gentamicin from poly(methyl methacrylate) (PMMA)-based bone cement. In addition, this method was used to compare the release profiles of Palacos R-40 bone cement with a two-solution bone cement developed in our laboratory and loaded with two different concentrations of gentamicin sulfate. Finally, the pH-based method was used to track the elution of gentamicin in both mixed and static conditions to determine the effect of mixing on the diffusion of gentamicin out of the cement. It was found that Palacos R-40 released 4.95 +/- 0.22 wt % of its gentamicin after 24 h in PBS solution. This data compares favorably with previously reported values of gentamicin elution from Palacos R-40, which ranged from 3 to 8 wt % of the total amount of incorporated gentamicin, depending on the size and the surface area of the samples. The results show that Palacos samples released 4.84 +/- 0.27 mg after 24 h, a two-solution cement loaded with an equivalent concentration of gentamicin sulfate released 3.81 +/- 0.52 mg, and two-solution cement loaded with twice the concentration of Palacos released 5.53 +/- 0.26 mg of gentamicin. A higher percentage of release was recorded from Palacos than from the two-solution bone cement, and the effect of PBS mixing conditions on the release kinetics was only significant in the early stages of release and not at 24 h. It was concluded that monitoring the pH is an effective technique to measure gentamicin release from PMMA-based bone cements in PBS solution.

Elution of metronidazole and gentamicin from polymethylmethacrylate beads.

To characterize the elution and bioactivity of metronidazole and gentamicin sulfate polymerized, individually and in combination, with polymethylmethacrylate (PMMA). In vitro experimental study. PMMA beads containing metronidazole (3 concentrations), gentamicin sulfate, or metronidazole and gentamicin sulfate were immersed in 5 mL of phosphate-buffered saline in triplicate. Eluent was replaced at specified time intervals for 1 or 21 days, and antibiotic concentrations were measured by high-performance liquid chromatography. Changes in antibiotic bioactivity attributable to polymerization or copolymerization of the antibiotics with PMMA, ethylene oxide sterilization, and storage of AIPMMA beads containing metronidazole were evaluated. Antibiotic elution patterns were similar for all groups. Day 1 elution for groups containing metronidazole or gentamicin individually represented a mean 63%-66% and 79%, respectively, of the 21-day total. Approximately 50% of the day 1 elution occurred during the first hour. The elution of metronidazole was dose dependent. The elution of metronidazole (day 3-21) and gentamicin (all days) was significantly greater when metronidazole and gentamicin were combined (P <.05). The addition of metronidazole delayed polymerization of PMMA. Neither polymerization nor copolymerization of metronidazole and gentamicin with PMMA, gas sterilization, or 2-month storage of beads containing metronidazole significantly affected antimicrobial bioactivity. Metronidazole elution from PMMA was dose dependent. Copolymerization of metronidazole and gentamicin sulfate in PMMA resulted in increased rates of elution. Intraoperative preparation of metronidazole-impregnated PMMA beads is not practical, but sterilization and storage for 2 months should not affect efficacy. The local delivery of biologically active metronidazole and gentamicin by elution from PMMA is feasible.

Antibiotic elution from bone cement: A study of common cement-antibiotic combinations.

The in vitro antibiotic elution characteristics (including the effects of cement fracture) of the following cements were studied: 1) CMW 1 with gentamicin, 2) Palacos R with gentamicin, 3) Palacos LV with gentamicin, 4) CMW 1 with gentamicin and vancomycin, 5) Palacos R with gentamicin and vancomycin, 6) CMW 1 with gentamicin and flucloxacillin, and 7) Palacos R with gentamicin and flucloxacillin. Elution of both gentamicin and vancomycin was satisfactory in all cases. There tended to be a peak of antibiotic release on cement fracture, suggesting sequestration of active antibiotic within deeper layers of the cement. Palacos LV exhibited the best antibiotic elution characteristics but with the highest post-fracture peak. Palacos R was superior to CMW 1. Flucloxacillin was present only until day 4. Adulteration of proprietary Palacos R/gentamicin with flucloxacillin produced prolonged high elution of gentamicin, possibly due to porosity. Flucloxacilloic acid (microbiologically inactive) was present from day 4 onwards after flucloxacillin was added to cement. These findings suggest that flucloxacillin is not a suitable additive to bone cement in revision surgery. (Hip International 2002; 1: 23-7).

In Vitro Elution of Gentamicin from Locally Implantable Beads

Locally implantable antibiotic beads have been approved for their efficacy in treating chronic osteomyelitis. This study aimed to compare the in vitro elution characteristics of commercial antibiotic cement (Septopal®) with those of custom-made gentamicin cement and gentamicin-loaded plaster of Paris. Septopal® had a better inhibitive effect than custom-made gentamicin cement and gentamicin-loaded plaster of Paris for both S. aureus and P. aeruginosa at one month. The elution of gentamicin from Septopal® declined gradually over one month in contrast to those of custom-made gentamicin cement and gentamicin-loaded plaster of Paris, which had a burst effect of elution and showed a small amount of gentamicin after one week. There was a significantly higher total amount of gentamicin eluted from Septopal® than from other types of noncommercially prepared beads. The variability of the inhibitive effect of custom-made gentamicin cement was more pronounced than those of Septopal® and gentamicin-loaded plaster of Paris groups. In conclusion, Septopal® has a better elution characteristic than custom-made gentamicin cement and gentamicin-loaded plaster of Paris in the in vitro study.

IN VITRO ELUTION OF GENTAMICIN FROM LOCALLY IMPLANTABLE BEADS

Locally implantable antibiotic beads have been approved for their efficacy in treating chronic osteomyelitis. This study aimed to compare the in vitro elution characteristics of commercial antibiotic cement (Septopal®) with those of custom-made gentamicin cement and gentamicin-loaded plaster of Paris. Septopal® had a better inhibitive effect than custom-made gentamicin cement and gentamicin-loaded plaster of Paris for both S. aureus and P. aeruginosa at one month. The elution of gentamicin from Septopal® declined gradually over one month in contrast to those of custom-made gentamicin cement and gentamicin-loaded plaster of Paris, which had a burst effect of elution and showed a small amount of gentamicin after one week. There was a significantly higher total amount of gentamicin eluted from Septopal® than from other types of noncommercially prepared beads. The variability of the inhibitive effect of custom-made gentamicin cement was more pronounced than those of Septopal® and gentamicin-loaded plaster of Paris groups. In conclusion, Septopal® has a better elution characteristic than custom-made gentamicin cement and gentamicin-loaded plaster of Paris in the in vitro study.

Biodegradable drug delivery systems for gentamicin release and treatment of synovial membrane infection.

This study investigated two biodegradable drug delivery systems (BDDS) for elution of gentamicin and elimination of synovial membrane infection. The effect of BDDS on control and infected synovial explants was determined. Synovial explants from four adult equine cadavers. First, BDDS were placed in phosphate buffered saline for 14 days. Eluent was tested for gentamicin concentration (G) and bioactivity. Second, synovial explants were divided into four groups (n = 14/group): Group 1 (control); Group 2 (infected control) 405 cfu Staphylococcus aureus added at 6 hours; Group 3 (antibiotic BDDS [Ab-BDDS]) Ab-BDDS added at 24 hours; Group 4 (infected Ab-BDDS) 405 cfu S. aureus added at 6 hours, Ab-BDDS added at 24 hours. Both types of Ab-BDDS were used (n = 7/type/group). Explants were incubated in standard medium for 4 days. Medium was cultured and analyzed for (G) and hyaluronic acid concentration (HA). Explants were analyzed for viability and morphologic changes. The Ab-BDDS released >500 microg/mL of active gentamicin for 10 days. In Group 3, infection was eliminated within 24 hours, but histologic scores did not return to normal. Viability was significantly reduced by infection, but if eliminated, viability tended to return to normal. In Group 3, the Ab-BDDS had no significant effect on viability or (HA). Histopathologic scores were significantly higher for infected synovium. Infection, even if treated, significantly reduced (HA). Both Ab-BDDS eliminated infection within 24 hours. However, synovial morphology, viability and function did not return to normal. The Ab-BDDS may be useful for treatment of synovial membrane infection.

Pharmacokinetics of a degradable drug delivery system in bone.

Local delivery of antibiotics via a degradable carrier has the potential for high local antibiotic levels and avoids systemic toxicity. Intravenous access, renal function monitoring, and later surgical removal may not be required when degradable local delivery modalities are used. This study examined the in vivo elution of gentamicin from processed bovine collagen (Type I). Gentamicin impregnated collagen (3 mg/kg) was implanted into the femoral medullary canal of 45 adult white rabbits. The gentamicin was released into the bone and averaged greater than 600 micrograms/ml during the initial 48 hours. Local bone levels fell to 144.40 +/- 229.84 micrograms/ml at 5 days and were subsequently greater than or equal to 10.30 +/- 5.02 micrograms/ml through Day 28. Serum levels reached an average peak of 1.25 +/- 0.29 micrograms/ml 5 hours after implantation and fell below 1.0 microgram/ml at 12 hours after implantation. Serum levels subsequently averaged less than or equal to 0.63 +/- 0.09 microgram/ml through Day 28. Collagen impregnated with gentamicin proved to be an effective degradable carrier of gentamicin in the healthy rabbit; it provided local bone concentrations above the minimum inhibitory concentration of gentamicin and serum concentrations below levels associated with systemic toxicity as long as 28 days after implantation.

Gentamicin distribution from a collagen carrier.

Local delivery of antibiotics by a degradable carrier has the potential for high local antibiotic levels and avoids systemic toxicity. Intravenous access, renal function monitoring, and subsequent surgical removal may not be required when degradable local delivery modalities are used. This study examined the in vivo elution of gentamicin from processed bovine collagen (type I) in 66 adult White rabbits. Collagen impregnated with gentamicin (3 mg/kg) was implanted into the vastus lateralis, and data were collected from 15 minutes to 28 days after implantation. Local tissue biopsies were taken a minimum of 2 mm from the implantation site. The gentamicin was released into the local tissue and averaged more than 3,800 micrograms/ml during the initial 4 hours after implantation. Local levels fell to 6.90 +/- 5.22 micrograms/ml at 24 hours and subsequently were 2.70 +/- 1.75 micrograms/ml or more through day 28. Serum levels reached an average peak of 4.04 +/- 1.75 micrograms/ml at 5 hours after implantation, decreased after the initial 24 hours, and subsequently were less than 0.41 +/- 0.20 microgram/ml through day 28. Collagen impregnated with gentamicin proved to be an effective degradable carrier of gentamicin in the healthy rabbit; it provided local tissue concentrations above the minimum inhibitory concentration and serum concentrations below levels associated with systemic toxicity for 28 days after implantation.

Gentamicin in Tissue and Whole Milk: An Improved Method for Extraction and Cleanup of Samples for Quantitation on HPLC

A new, inexpensive, and rapid procedure for the extraction of gentamicin from animal tissue and whole milk samples is described. Tissue samples from gentamicin-treated calves were homogenized in a pH 8.8 extraction buffer, mixed, filtered, and centrifuged. The resulting supernatant fractions were extracted using bifunctional hydrophobic/ion exchange solid phase cartridges. The isolated gentamicin was derivatized with a chromophore and analyzed using high-performance liquid chromatography. Whole milk samples were similarly extracted and analyzed. The resulting chromatograms showed exceptionally clean samples with no interfering peaks in the area of gentamicin elution. This allowed good separation and detection of all four isomers of gentamicin. The detection limit for gentamicin was 0.6 μg/mL in whole milk and 1 μg/g in tissue samples. The coefficients of variation were 2.5% for whole milk and 8.1% for tissue samples. The efficiency of recovery was greater than 90%.