Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies.
OBJECTIVE
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.


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.
Orthopaedic Surgeon, Lithuanian University of Health, Eivenių str. 2, LT-50009 Kaunas, Lithuania.
M
M
Stravinskas
Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
P
P
Horstmann
The Bone Infection Unit, Nuffield Orthopedic Centre, Oxford University Hospitals, Windmill Road, Headington, Oxford OX3 7HE, UK.
J
J
Ferguson
Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
W
W
Hettwer
Department of Orthopedics, Lund University Hospital, SE-221 85 Lund, Sweden malin@lalit.se.
M
M
Nilsson
Orthopaedic Surgeon, Lithuanian University of Health, Eivenių str. 2, LT-50009 Kaunas, Lithuania.
S
S
Tarasevicius
Musculoskeletal Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
M M
MM
Petersen
The Bone Infection Unit, Nuffield Orthopedic Centre, Oxford University Hospitals, Windmill Road, Headington, Oxford OX3 7HE, UK.
M A
MA
McNally
Department of Orthopedics, Lund University Hospital, SE-221 85 Lund, Sweden.
L
L
Lidgren
Antibiotics; Bone graft substitute; Gentamicin; Infection; Prevention
BMC Musculoskelet Disord. 2015 May 13;16:115
25968241
Acta Orthop Scand. 1997 Feb;68(1):34-40
9057565
Clin Orthop Relat Res. 1983 Dec;(181):99-106
6641072
Clin Orthop Relat Res. 1993 Oct;(295):102-11
8403633
Clin Orthop Relat Res. 2004 Oct;(427):101-6
15552144
J Bone Joint Surg Br. 2006 Sep;88(9):1149-57
16943463
J Trauma. 1998 Oct;45(4):758-64
9783617
Semin Plast Surg. 2009 May;23(2):100-7
20567732
J Bone Joint Surg Am. 2014 Mar 5;96(5):380-6
24599199
Antimicrob Agents Chemother. 2008 Mar;52(3):920-6
18172002
J Shoulder Elbow Surg. 2014 Sep;23(9):1272-6
24613181
J Orthop Trauma. 2010 Sep;24(9):587-91
20736800
Antimicrob Agents Chemother. 1996 Dec;40(12):2675-9
9124821
Antimicrob Agents Chemother. 2006 Aug;50(8):2626-31
16870751
Acta Orthop Scand. 1980 Dec;51(6):863-9
7010892
J Biomater Appl. 2011 Nov;26(4):491-506
20819915
Infect Dis Clin North Am. 1990 Sep;4(3):391-408
2212596
Biomaterials. 2003 May;24(10):1829-31
12593965
Injury. 2010 Oct;41(10 ):1053-9
20541756
Antimicrob Agents Chemother. 2003 Jul;47(7):2283-92
12821480
Bone Joint J. 2016 Sep;98-B(9):1289-96
27587534
Bone Joint Res. 2014 Jul;3(7):223-9
25005841
Can J Surg. 2012 Oct;55(5):E8-9
22992425
J Trauma. 2000 Feb;48(2):246-55
10697082
Ann Epidemiol. 2014 Sep;24(9):660-5
25088754
Acta Orthop. 2014 Jun;85(3):218-20
24758324
J Bone Joint Surg Br. 1995 Jan;77(1):93-7
7822405
J Antimicrob Chemother. 2007 Feb;59(2):246-53
17220162
Ann Chir Plast Esthet. 2000 Jun;45(3):346-53
10929461
J Biomed Mater Res B Appl Biomater. 2010 Jan;92(1):281-6
19904822
J Antimicrob Chemother. 2004 Dec;54(6):1013-8
15537698
Antimicrob Agents Chemother. 2015 Jan;59(1):111-20
25313221
N Engl J Med. 2004 Oct 14;351(16):1645-54
15483283
Clin Orthop Relat Res. 1996 Aug;(329):273-80
8769462
J Arthroplasty. 2008 Aug;23(5):762-71
18534525
Clin Orthop Relat Res. 2003 Sep;(414):7-24
12966271
J Biomed Mater Res B Appl Biomater. 2009 Apr;89(1):102-13
18698616
Acta Biomater. 2011 Mar;7(3):1274-80
21081183
Acta Orthop Scand. 1992 Jun;63(3):301-4
1609595
J Bone Joint Surg Br. 1989 Nov;71(5):851-5
2584258
Biomaterials. 2007 Nov;28(32):4880-8
17697708
Curr Microbiol. 1998 Apr;36(4):212-5
9504987
J Orthop Trauma. 2011 Mar;25(3):156-61
21278604
J Bone Joint Surg Br. 2004 Jan;86(1):120-5
14765879
Injury. 2011 Sep;42 Suppl 2:S82-6
21762911
Acta Orthop. 2010 Dec;81(6):660-6
21110700
J Orthop Res. 2011 Jul;29(7):1070-4
21567453
Cell Tissue Bank. 2006;7(4):319-23
16710632
Hip Int. 2012 Jul-Aug;22 Suppl 8:S62-8
22956385
Clin Orthop Relat Res. 1986 Apr;(205):171-83
3516500
J Gastrointest Surg. 2007 Feb;11(2):138-42
17390162
Orthop Clin North Am. 2015 Oct;46(4):495-510
26410638
Acta Orthop Scand. 1989 Dec;60(6):668-9
2624085
Acta Orthop Scand. 1980 Feb;51(1):49-56
7376844
Lancet. 2012 Apr 7;379(9823):1331-40
22398175