Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute

Abstract

ObjectivesDeep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing.The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets.DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory.Materials and MethodsWe present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer’s solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis.ResultsThe release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years).ConclusionsThis new biphasic bone substitute containing antibiotics provides safe prevention of bone infections in a range of clinical situations. The in vitro test method predicts the in vivo performance and makes it a reliable tool in the development of future antibiotic-eluting bone-regenerating materials.Cite this article: M. Stravinskas, P. Horstmann, J. Ferguson, W. Hettwer, M. Nilsson, S. Tarasevicius, M. M. Petersen, M. A. McNally, L. Lidgren. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies. Bone Joint Res 2016;5:427–435. DOI: 10.1302/2046-3758.59.BJR-2016-0108.R1.

The Use of Calcium Sulphate beads in Periprosthetic Joint Infection, a systematic review

“…PMMA beads require subsequent removal and may develop biofilm on their surface if left in situ for long periods (9). Some authors have shown a relatively short period of antibiotic release with a decrease in local concentrations to 10% of the initial levels within 24 hours (10). Currently, CS beads are used as an alternative void filler to PMMA in the presence of infection, non-union or bone loss (11).…”

Developments in Antibiotic-Eluting Scaffolds for the Treatment of Osteomyelitis

“…In another study that used gentamicin-eluting PMMA, 90% of the bacteria isolated were found to be resistant compared to 16% for plain cement [32]. It has also been suggested that chronic, unnecessary exposure to drugs such as gentamicin may cause nephrotoxicity, even at a low dose [33]. Those with renal impairment are especially at risk [33].…”

“…It has also been suggested that chronic, unnecessary exposure to drugs such as gentamicin may cause nephrotoxicity, even at a low dose [33]. Those with renal impairment are especially at risk [33]. Moreover, when complete elution from a non-biodegradable scaffold is eventually achieved, the material acts as a foreign body and can become colonised, leading to recurrent infections [34].…”

First report on treating spontaneous infectious spondylodiscitis of lumbar spine with posterior debridement, posterior instrumentation and an injectable calcium sulfate/hydroxyapatite composite eluting gentamicin: a case report

“…In our opinion, the advantage of the injectable calcium sulfate/hydroxyapatite composite plus gentamicin is the high local concentration of gentamicin at the desired location [24], the complete resorption of the BGS, and its osteoconductivity.…”