In vivo pharmacokinetics of a gentamicin-loaded collagen sponge in acute periprosthetic infection: Serum values in 19 patients

Swieringa, Anne J; Goosen, Jon H. M.; Jansman, Frank G A; Tulp, Niek J. A.

doi:10.1080/17453670810016650

Cited by 41 publications

(32 citation statements)

References 24 publications

(29 reference statements)

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“…We estimate the volume of G-PNDJ hydrogel that might be used in a human case would be approximately 15 to 20 mL, one-sixth the volume that led to renal toxicity in rats. When similar amounts of gentamicin are delivered using a collagen sponge as the delivery vehicle, the release is more rapid [59] and this is reported to be well tolerated in human patients [60], understanding that pharmacokinetics of gentamicin in human patients are highly variable [65].…”

Section: Discussionmentioning

confidence: 99%

Local Gentamicin Delivery From Resorbable Viscous Hydrogels Is Therapeutically Effective

Overstreet

McLaren

Calara

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Local delivery can achieve the high antimicrobial concentrations necessary to kill biofilm-related microbes. Degradation times for resorbable carriers are too long. Hydrogels (gels of hydrophilic polymer in water) can degrade faster but release antimicrobials too quickly. We previously developed hydrogels based on the copolymer poly(N-isopropylacrylamide-co-dimethyl-c-butyrolactone acrylate-co-Jeffamine 1 M-1000 acrylamide) (PNDJ) with delivery times of several days with complete degradation in less than 6 weeks. Questions/purposes We asked: (1) What is the elution profile of gentamicin from PNDJ hydrogels? (2) Is gentamicin released from gentamicin-loaded PNDJ (G-PNDJ) hydrogel effective for treatment of orthopaedic infection? (3) Does local gentamicin delivery from G-PNDJ hydrogel cause renal dysfunction? Methods (1) Two formulations of G-PNDJ, lower dose (1.61 wt%) and higher dose (3.14 wt%), five samples each, were eluted in buffered saline under infinite sink conditions. (2) Infections were induced in 16 New Zealand White rabbits by inserting a Kirschner wire in a devascularized radius segment and inoculating with 7.5 9 10 6 colony-forming units Staphylococcus aureus. At 3 weeks, débridement was performed and a new Kirschner wire was placed in the dead space. Treatment was randomized to higher-dose G-PNDJ or no hydrogel. No systemic antimicrobials were used. Positive culture and acute inflammation on histology were used to determine the presence of infection 4 weeks postdébridement. (3) 3.14 wt% G-PNDJ, 0.75, 1.5, or 3.0 mL, was injected subcutaneously in nine Sprague-Dawley rats, three of each dose. Serum gentamicin, blood urea nitrogen, and creatinine were measured on Days 1, 3, 7, 14, and 28. Results (1) Gentamicin release was sustained over 7 days with the higher-dose formulation release profile similar to release from high-dose antimicrobial-loaded bone cement.(2) Four weeks postdébridement, infection was present in eight of eight no-hydrogel rabbits but zero of eight rabbits treated with G-PNDJ hydrogel (p \ 0.001). (3) Blood urea nitrogen and creatinine were transiently elevated

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Section: Discussionmentioning

confidence: 99%

Local Gentamicin Delivery From Resorbable Viscous Hydrogels Is Therapeutically Effective

Overstreet

McLaren

Calara

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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“…Antibiotic-loaded collagen sponges provide high local concentrations of antibiotic in a biocompatible matrix [14,24]. A possible drawback to these sponges is potentially toxic serum levels of gentamicin in the initial treatment cycle [34]. A limitation with use of calcium sulfate, collagen, and other local delivery systems is a lack of data validating each particular system with multiple antibiotics.…”

Section: Introductionmentioning

confidence: 99%

Chitosan Sponges to Locally Deliver Amikacin and Vancomycin: A Pilot In Vitro Evaluation

Noel

Courtney

Bumgardner

et al. 2010

Clinical Orthopaedics &Amp; Related Research

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Background Open orthopaedic wounds are ideal sites for infection. Preventing infection in these wounds is critical for reducing patient morbidity and mortality, controlling antimicrobial resistance and lowering the cost of treatment. Localized drug delivery has the potential to overcome the challenges associated with traditional systemic dosing. A degradable, biocompatible polymer sponge (chitosan) that can be loaded with clinician-selected antibiotics at the point of care would provide the patient and clinician with a desirable, adjunctive preventive modality. Questions/purposes We asked (1) if an adaptable, porous chitosan matrix could absorb and elute antibiotics for 72 hours for potential use as an adjunctive therapy to débri-dement and lavage; and (2) if the sponges could elute levels of antibiotic that would inhibit growth of Staphylococcus aureus and Pseudomonas aeruginosa? Methods We fabricated a degradable chitosan sponge that can be loaded with antibiotics during a 60-second hydration in drug-containing solution. In vitro evaluation determined amikacin and vancomycin release from chitosan sponges at six time points. Activity tests were used to assess the release of inhibitory levels of amikacin and vancomycin. Results Amikacin concentration was 881.5 lg/mL after 1 hour with a gradual decline to 13.9 lg/mL after 72 hours. Vancomycin concentration was 1007.4 lg/mL after 1 hour with a decrease to 48.1 lg/mL after 72 hours. Zone of inhibition tests were used to verify inhibitory levels of drug release from chitosan sponges. A turbidity assay testing activity of released amikacin and vancomycin indicated inhibitory levels of elution from the chitosan sponge. Clinical Relevance Chitosan sponges may provide a potential local drug delivery device for preventing musculoskeletal infections.

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“…In contrast to bacterial infections, which might be locally treated with insertion of antibiotic-loaded collagen sponges [33] or implantation of cement device [34], it is not known that antifungal local therapy can be a reliable treatment [35]. To the best of our knowledge, there are no current guidelines suggesting that fungal periprosthetic joint infections should be managed locally.…”

Section: Discussionmentioning

confidence: 94%

Systemic Review of Published Literature on Candida Infection Following Total Hip Arthroplasty

Kim

Huh²,

Odrobina

2014

Mycopathologia

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Candida species (Candida spp.) infection following total hip arthroplasty (THA) is a rare but potentially devastating complication. The purpose of this study was to provide an evidence-based summarization of the treatment and outcome of Candida spp. infection after THA. We conducted a systemic review of the literature and pooled analysis of Candida spp. infection after THA published between 1950 and 2014. A total of 20 articles with 37 patients were identified. Median time between THA and readmission for Candida spp. infection was 25 months (range 0.5-184 months). Thirty-two patients (87%) underwent removal of the prosthesis for initial surgical treatment. All patients were treated with systemic antifungal medication therapy for various durations after the surgical procedure or primary therapy without surgical procedures except for one patient who was treated with only amphotericin B joint cavity irrigation after removal of the prosthesis. Relapse of the infection occurred in three patients who had retention of the original prosthesis. There were three deaths related to the Candida spp. infection following THA owing to uncontrolled Candida spp. infection and deteriorating candidemia sepsis. Of note, among 15 patients who underwent two-stage exchange arthroplasty, there was one patient (7%) who developed complication (death) while other 14 patients had uncomplicated recovery. In conclusion, surgical debridement with removal of the original prosthesis or two-stage exchange arthroplasty with combination of adequate systemic antifungal therapy is highly recommended in the treatment of Candida spp. infection following THA.

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In vivo pharmacokinetics of a gentamicin-loaded collagen sponge in acute periprosthetic infection: Serum values in 19 patients

Abstract: The application of 2 to 5 130-mg gentamycin-loaded collagen fleeces may be useful as an adjuvant treatment for implant-related infections, since no toxic concentrations were measured 24 hours postoperatively.

Cited by 41 publications

References 24 publications

Local Gentamicin Delivery From Resorbable Viscous Hydrogels Is Therapeutically Effective

Local Gentamicin Delivery From Resorbable Viscous Hydrogels Is Therapeutically Effective

Chitosan Sponges to Locally Deliver Amikacin and Vancomycin: A Pilot In Vitro Evaluation

Systemic Review of Published Literature on Candida Infection Following Total Hip Arthroplasty

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