Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute:<i>In vitro</i> and clinical release studies

OBJECTIVES: Deep 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 METHODS: We 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. RESULTS: The 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). CONCLUSIONS: This 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 CONSTITUTIONAL POSSIBILITIES FOR GOVERNMENTAL FINANCIAL ASSISTANCE TO NONPUBLIC SCHOOL PARENTS

The purpose of the study was to discover the constitutional possibilities for federal financial assistance to nonpublic school parents in a multi-disciplinary manner. Special consideration was given to the Supreme Court\u27s perception of the nature and purpose of Catholic schools and to diocesan school policy handbooks for refutation or substantiation of the Court\u27s impressions of Catholic schools. Major finds at the public policy level were that aid: has ample precedents; would improve educational quality because of competition; is supported by a majority of Americans but has been opposed by many for reasons of anti-Catholicism. Constitutional aspects of the question revealed that: The First Amendment\u27s prohibition of an establishment of religion was primarily designed to prevent the erection of a governmentally sponsored national church; other western democracies prove that separation of Church and State is possible even with governmental support of denominational schools, as does the first 125 years of this nation\u27s history. Difficulties with financial aid have surfaced at the Supreme Court level, where the Court has mistakenly stereotyped Catholic education as a monolithic system, with no support for their views in the diocesan policy manuals. Yet another insight gained was the strong, consistent relationship that exists between a justice\u27s image of the parochial school and how he voted on a given case before him, and how special interest groups or those with a history of anti-Catholic bias have influenced the Court. The study concluded with recommendations for the Supreme Court, nonpublic school personnel and parents, legislative bodies and public schools personnel

Vancomycin elution from a biphasic ceramic bone substitute

Objectives: The aim of this study was to analyze drain fluid, blood, and urine simultaneously to follow the long-term release of vancomycin from a biphasic ceramic carrier in major hip surgery. Our hypothesis was that there would be high local vancomycin concentrations during the first week with safe low systemic trough levels and a complete antibiotic release during the first month.Methods: Nine patients (six female, three male; mean age 75.3 years (sd 12.3; 44 to 84)) with trochanteric hip fractures had internal fixations. An injectable ceramic bone substitute, with hydroxyapatite in a calcium sulphate matrix, containing 66 mg of vancomycin per millilitre, was inserted to augment the fixation. The vancomycin elution was followed by simultaneously collecting drain fluid, blood, and urine.Results: The antibiotic concentration in the drain reached a peak during the first six hours post-surgery (mean 966.1 mg/l), which decreased linearly to a mean value of 88.3 mg/l at 2.5 days. In the urine, the vancomycin concentration reached 99.8 mg/l during the first two days, followed by a logarithmic decrease over the next two weeks to reach 0 mg/l at 20 days. The systemic concentration of vancomycin measured in blood serum was low and decreased linearly from 2.17 mg/l at one hour post-surgery to 0 mg/l at four days postoperatively.Conclusion: This is the first long-term pharmacokinetic study that reports vancomycin release from a biphasic injectable ceramic bone substitute. The study shows initial high targeted local vancomycin levels, sustained and complete release at three weeks, and systemic concentrations well below toxic levels. The plain ceramic bone substitute has been proven to regenerate bone but should also be useful in preventing bone infection.Cite this article: M. Stravinskas, M. Nilsson, A. Vitkauskiene, S. Tarasevicius, L. Lidgren. Vancomycin elution from a biphasic ceramic bone substitute. Bone Joint Res 2019;8:49-54. DOI: 10.1302/2046-3758.82.BJR-2018-0174.R2