DOI: http://dx.doi.org/10.18203/issn.2455-4510.IntJResOrthop20211599

Does local implantation of gentamicin impair renal function in patients undergoing surgery for chronic bone infection?

Ross Muir, Catherine Birnie, Robert Hyder-Wilson, Jamie Ferguson, Martin A. McNally

Abstract


Background: The treatment of chronic bone infection often involves excision of dead bone and implantation of biomaterials which elute antibiotics. Gentamicin is a preferred drug for local delivery, but its systemic use carries a well-established risk of nephrotoxicity.  We aim to establish the risk of acute kidney injury (AKI) with local delivery in a ceramic carrier.

Methods: 163 patients with Cierny-Mader type 3 or 4 chronic osteomyelitis had a single-stage operation including filling of the osseous defect with a calcium sulphate-hydroxyapatite carrier containing gentamicin. Mean gentamicin dosing was 191.3 mg (maximum 525 mg). Glomerular filtration rate (GFR) was calculated pre-operatively and during the first seven days post-operatively. Renal impairment was graded using the chronic kidney disease (CKD) staging system, and AKI was assessed using the RIFLE criteria.

Results: 155 cases had adequate data to allow calculation of pre- and post-operative GFR. 7 had pre-existing renal disease. 70 patients (45.2%) had a temporary GFR drop post-operatively, with the greatest decrease occurring at a mean of 3.06 days following surgery. Twenty cases had a >10% decline in GFR, but 12 resolved within 7 days. 7 patients transiently fell into the “Risk” category according to RIFLE criteria, but no patient had a change consistent with “Injury”, “Failure” or “Loss” of renal function and none had clinical signs of new acute renal impairment post-operatively. 

Conclusions: Renal function is not significantly affected by local implantation of gentamicin up to 525 mg. The presence of pre-existing renal disease is not a contraindication to local gentamicin therapy.

 


Keywords


Osteomyelitis, Gentamicin, Nephrotoxicity, Surgery, Biomaterial

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References


McNally M, Nagarajah K. Osteomyelitis. Orthop Trauma. 2010;24(6):416-29.

Metsemakers W-J, Morgenstern, M, Senneville E. General treatment principles for fracture-related infection: recommendations from an international expert group. Arch Orthop Trauma Surg. 2020;140:1013-27.

Chan JKK, Ferguson JY, Scarborough M, McNally MA, Ramsden AJ. Management of Post-Traumatic Osteomyelitis in the Lower Limb: Current State of the Art. Indian J Plast Surg. 2019;52(1):62‐72.

Cierny III G, DiPasquale D. Treatment of chronic infection. J Am Acad Orthop Surg. 2006;14:S105-10.

BMJ Best Practice Guideline for osteomyelitis. Available from: https://bestpractice.bmj.com/topics/en-gb/354. Accessed 8 November, 2020.

Dudareva M, Hotchen AJ, Ferguson J, Hodgson S, Scarborough M, Atkins BL et al. The microbiology of osteomyelitis: changes over ten years. J Infection. 2019;79:189-98.

Li HK, Rombach I, Zambellas R. Oral versus Intravenous Antibiotics for Bone and Joint Infection. N Engl J Med. 2019;380(5):425‐36.

Kruse Jensen L, Koch J, Hendriksen L, Bue M, Tottrup M, Hanberg P et al. Suppurative Inflammation and Local Tissue Destruction Reduce the Penetration of Cefuroxime to Infected Bone Implant Cavities. J Comparative Pathol. 2017;157(4):308-16.

Jensen LK, Bjarnsholt T, Kragh KN, Aalbæk B, Henriksen NL, Blirup SA et al. In vivo gentamicin susceptibility test for prevention of bacterial biofilms in bone tissue and on implants. Antimicrob Agents Chemother. 2019;63:e0188.

Rand BC, Penn-Barwell JG, Wenke JC. Combined local and systemic antibiotic. delivery improves eradication of wound contamination: an animal experimental model of contaminated fracture. Bone Joint J. 2015;97-B:1423-7.

Ruppen C, Hemphill A, Sendi P. In-vitro activity of gentamicin as adjunct to penicillin against biofilm group B Streptococcus. J Antimicrob Chemother. 2017;72:444-7.

Wahlig H, Dingeldein E. Antibiotics and bone cements. Experimental and clinical long-term observations. Acta Orthop Scand. 1980;52(1):49-56.

Moojen DJ, Hentenaar B, Vogely CH. In vitro release of antibiotics from commercial PMMA beads and articulating hip spacers. J Arthroplasty. 2008;23:1152-6.

Stravinskas M, Horstmann P, Ferguson J, Hettwer W, Nilsson M, Tarasevicius S et al. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute - In vitro and clinical release studies. Bone Joint Res. 2016;5:427-35

Ferguson J, Diefenbeck M, McNally M. Ceramic bio composites as biodegradable antibiotic carriers in the treatment of bone infections. J Bone Joint Infect. 2017;2:41-54.

Selby NM, Shaw S, Woodier N, Fluck RJ, Kolhe NV. Gentamicin-associated acute kidney injury. QJM. 2009;102(12):873-80.

Hayward RS, Harding J, Molloy R, Land L, Longcroft-Neal K, Moore D, Ross JDC. Adverse effects of a single dose of gentamicin in adults: a systematic review. Br J Clin Pharmacol. 2018;84:223-38.

Walenkamp GH, Vree TB, van Rens TJ. Gentamicin-PMMA beads. Pharmacokinetic and nephrotoxicological study. Clin Orthop Relat Res. 1986;205:171-83.

Metsemakers W-J, Fragomen AT, Moriarty F, Morgenstern M, Egol KA, Zalavras C et al. Evidence-based recommendations for local antimicrobial strategies and dead space management in Fracture-related Infection. J Orthop Trauma. 2019;34:18-29.

Oliver RA, Lovric V, Christou C, Walsh WR. Evaluation of comparative soft tissue response to bone void fillers with antibiotics in a rabbit intramuscular model. J Biomaterials Applications. 2019;34(1):117-29.

McNally M, Ferguson J, Diefenbeck M. Single-stage treatment of chronic osteomyelitis with a new absorbable, gentamicin-loaded, calcium sulphate/hydroxyapatite bio-composite. A prospective series of 100 cases. Bone Joint J. 2016;98-B:1289-96.

Levey AS, Stevens LA, Schmid CH. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604-12.

K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis. 2002;39:S1-266.

Bellomo R, Ronco C, Kellum JA. Acute renal failure-definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8:R204.

Klemm K. The treatment of chronic bone infections with gentamicin-PMMA-chains and beads. H Contzen (Ed.), Gentamycin-PMMA-Kette, Unfallchirurgie. 1977;3(1):20-5.

Neut D, van de Belt H, van Horn JR, van der Mei HC, Busscher HJ. Residual gentamicin-release from antibiotic-loaded polymethylmethacrylate beads after 5 years of implantation. Biomaterials. 2003;24(10):1829-31.

Thomes B, Murray P, Bouchier-Hayes D. Development of resistant strains of Staphylococcus epidermidis on gentamicin-loaded bone cement in vivo. J Bone Joint Surg Br. 2002;84:758-60.

Ferguson J, Athanasou N, Diefenbeck M, McNally M. Radiographic and Histological Analysis of a Synthetic Bone Graft Substitute Eluting Gentamicin in the Treatment of Chronic Osteomyelitis. J Bone Jt Infect. 2019;4(2):76‐84.

Smith CR, Lipsky JJ, Laskin OL, Hellmann DB, Mellits ED, Longstreth J et al. Double-blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin. N Engl J Med. 1980;302:1106-9.

Matzke GR, Lucarotti RL, Shapiro HS. Controlled comparison of gentamicin and tobramycin nephrotoxicity. Am J Nephrol. 1983;3(1):11-7.

Nicolau DP, Freeman CD, Belliveau PP, Nightingale CH, Ross JW, Quintiliani R. Experience with a once-daily aminoglycoside program administered to 2,184 adult patients. Antimicrob Agents Chemother. 1995;39(3):650‐55.

Uchino S, Bellomo R, Goldsmith D. An assessment of the RIFLE criteria for acute renal failure in hospitalized patients. Crit Care Med. 2006;34:1913-7.

Ostermann M, Chang RW. Acute kidney injury in the intensive care unit according to RIFLE. Crit Care Med. 2007;35:1837-43.

Hoste EA, Clermont G, Kersten A. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care. 2006;10:R73.

Bell S, Davey P, Nathwani D, Marwick C, Vadiveloo T, Sneddon J et al. Risk of AKI with Gentamicin as Surgical Prophylaxis. JASN. 2014;25(11):2625-32.

Mergenhagen KA, Borton AR. Vancomycin nephrotoxicity: a review. J Pharm Pract. 2014;27(6):545‐53.

Rybak MJ, Abate BJ, Kang SL, Ruffing MJ, Lerner SA, Drusano GL. Prospective evaluation of the effect of an aminoglycoside dosing regimen on rates of observed nephrotoxicity and ototoxicity. Antimicrob Agents Chemother. 1999;43(7):1549‐55.

Moenster RP, Linneman TW, Finnegan PM, Hand S, Thomas Z, McDonald JR. Acute renal failure associated with vancomycin and β-lactams for the treatment of osteomyelitis in diabetics: piperacillin-tazobactam as compared with cefepime. Clin Microbiol Infect. 2014;20(6):O384‐9.

Doi K, Yuen PS, Eisner C, Hu X, Leelahavanichkul A, Schnermann J et al Reduced production of creatinine limits its use as marker of kidney injury in sepsis. J Am Soc Nephrol. 2009;20(6):1217-21.

Clark WR, Mueller BT, Kraus MA, Macias WL. Quantification of creatinine kinetic parameters in patients with acute renal failure. Kidney Int. 1998;54(2):554-60.