Research Article| Volume 61, ISSUE 2, P239-247, March 2022

Complex Foot Infection Treated With Surgical Debridement and Antibiotic Loaded Calcium Sulfate—A Retrospective Cohort Study of 137 Cases


      Complex foot infections involving bone and soft tissue in patients with co-morbidities such as diabetes and peripheral arterial disease (PAD) are a cause of significant hospital admission. They are associated with substantial economic costs to health services worldwide. Historically, severe foot infection has been treated with surgical debridement and prolonged courses of systemic antibiotics. Prolonged systemic antibiotic use increases the risk of drug side effects, antimicrobial resistance and Clostridium difficile infection. The purpose of this study was to investigate whether surgical debridement and implantation of antibiotic loaded calcium sulfate is effective in the resolution of foot infection and wound healing. A retrospective cohort study of 137 consecutive cases of osteomyelitis (127) or significant soft tissue infection (10) over 62 months from 02/2013 to 04/2018 was conducted following local ethical approval. All cases of infection were treated with surgical debridement and local antibiotic-loaded calcium sulfate. The primary outcomes of infection resolution, time to healing and duration of postoperative antibiotics were measured. In 137 cases, 88.3% of infections resolved. Infection was eradicated in 22 patients without postoperative systemic antibiotics. About 82.5% of wounds healed, with an average healing time of 11.3 weeks. Healing time was significantly increased for the co-morbidities of diabetes and PAD (p =< .05) and for those requiring prolonged systemic postoperative antibiotics. Conservative surgical debridement and implantation of local antibiotic impregnated calcium sulfate is safe and effective in managing complex foot infections. We advocate early surgical intervention before deeper tissue involvement to help preserve lower limb structure and function.

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        • Zhang P
        • Lu J
        • Jing Y
        • Tang S
        • Zhu D
        • Bi Y.
        Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis.
        Ann Med. 2017; 49:2: 106-116
        • Armstrong DG
        • Boulton AJM
        • Bus SA.
        Diabetic foot ulcers and their recurrence.
        N Engl J Med. 2017; 376: 2367-2375
        • Hobizal KB
        • Wukich DK.
        Diabetic foot infection: current concept review.
        Diabetic Foot Ankle. 2012; 3: 18409
        • Panagopoulos P
        • Drosos G
        • Maltezos E
        • Papanas N.
        Local antibiotic delivery systems in diabetic foot osteomyelitis: time for one step beyond?.
        Int J Lower Extremity Wounds. 2015; 14: 87-91
        • Lazaro-Martinez J
        • Aragon-Sanchez J
        • Garcia-Morales E.
        Antibiotics versus conservative surgery for treating diabetic foot osteomyelitis: a randomized comparative trial.
        Diabetes Care. 2014; 37: 789-795
        • Iannuccelli V
        • Coppi G
        • Bondi M
        • Pinelli M
        • Mingione A
        • Cameroni R.
        Biodegrad-able intraoperative system for bone infection treatment II. In vivo evaluation.
        Int J Pharm. 1996; 143: 187-194
        • Fleiter N
        • Walter G
        • Bösebeck H
        • Vogt S
        • Büchner H
        • Hirschberger W
        • Hoff-Mann R.
        Clinical use and safety of a novel gentamicin-releasing resorbable bone graft substitute in the treatment of osteomyelitis/osteitis.
        Bone Joint Res. 2014; 3: 223-229
        • Papegelopoulos PJ
        • Mavrogenis AF
        • Tsiodras S
        • Vlastou C
        • Giamarellou H
        • Sou-cacos PN
        Calcium sulphate delivery system with tobramycin for the treatment of chronic calcaneal osteomyelitis.
        J Int Med Res. 2006; 34: 704-712
        • Wang Y
        • Wang X
        • Li H
        • Xue D
        • Shi Z
        • Qi Y
        • Ma Q
        • Pan Z
        Assessing the character of the rhBMP-2- and vancomycin-loaded calcium sulphate composites in vitro and in vivo.
        Arch Orthop Trauma Surg. 2011; 131: 991-1001
        • Panagopoulos P
        • Tsaganos T
        • Plachouras D
        • Carrer D-P
        • Papadopoulos A
        • Giamarellou H
        • Kanellakopoulou K
        In vitro elution of moxifloxacin and fucidic acid by a synthetic crystallic semihydrate form of calcium sulphate (stimulan).
        Int J Antimicrob Agents. 2008; 32: 485-487
        • Gauland C.
        Managing lower extremity osteomyelitis locally with surgical debridement and synthetic calcium sulphate antibiotic tablets.
        Adv Skin Wound Care. 2011; 24: 515-523
        • Smits WK
        • Lyras D
        • Lacy B
        • Wilcox MH
        • Kuijper EJ.
        Clostridium difficile infection.
        Nat Rev Disease Primers. 2016; 2201620
        • Morley R
        • Webb
        An unusual complication following charcot neuroarthropathy.
        Diabetic Foot J. 2018; 21: 107-114
        • Barber A
        • Morley R
        • Webb F.
        Incision and drainage of a septic abscess following corticosteroid injection for plantar fasciitis.
        Podiatry Now. 2018; 21: 14-18
        • Morley R
        • Lopez F
        • Webb F.
        Calcium sulphate as a drug delivery system in a deep diabetic foot infection.
        Foot. 2016; 27: 36-40
        • Jogia RM
        • Modha DE
        • Nisal K
        • Berrington R
        • Kong M-F
        Use of highly purified synthetic calcium sulfate impregnated with antibiotics for the management of diabetic foot ulcers complicated by osteomyelitis diabetes care.
        Diabetes Care. 2015; 38: e79-e80
        • Agarwal S
        • Healey B.
        The use of antibiotic impregnated absorbable calcium sulphate beads in management of infected joint replacement prostheses.
        J Arthrosc Joint Surg. 2014; 1: 72-75
        • Kumar YC
        • Nalini KB
        • Menon J
        • Patro DK
        • Banerji BH.
        Calcium sulfate as bonegraft substitute in the treatment of osseous bone defects, a prospective study.
        J Clin Diagn Res. 2013; 7: 2926-2928
        • Gitelis S
        • Brebach GT.
        The treatment of chronic osteomyelitis with a biodegradable antibiotic-impregnated implant.
        J Orthop Surg. 2002; 10: 53-60
        • Wahl P
        • Livio F
        • Jacobi M
        • Gautier E
        • Buclin T
        Systemic exposure to tobramycin after local antibiotic treatment with calcium sulphate as carrier material.
        Arch Orthop Trauma Surg. 2011; 131: 657-662
        • Laycock PA
        • Cooper JJ
        • Howlin RP
        • Delury C
        • Aiken S
        • Stoodley P
        In vitro efficacy of antibiotics released from calcium sulfate bone void filler beads.
        Materials. 2018; 11: 2265
        • Kanellakopoulou K
        • Galanopoulos I
        • Soranoglou V
        • Tsaganos T
        • TziortziotiV MI
        • Papalois A
        • Giamarellou H
        • Giamarellos-Bourboulis J.
        Treatment of experimental osteomyelitis caused by methicillin-resistant Staphylococcus aureus with a synthetic carrier of calcium sulphate (stimulan) releasing moxifloxacin.
        Int J Antimicrobiol Agents. 2009; 33: 354-359
        • Song JW
        • Chung KC.
        Observational studies: cohort and case-control studies.
        Plast Reconstr Surg. 2010; 126: 2234-2242
        • Grayson ML
        • Gibbons GW
        • Balogh K
        • Levin E
        • Karchmer AW.
        Probing to bone in infected pedal ulcers. A clinical sign of underlying osteomyelitis in diabetic patients.
        JAMA. 1995; 273: 721-723
        • Lipsky BA
        • Berendt AR
        • Cornia PB
        • Pile JC
        • Peters EJG
        • Armstrong DG
        • Gunner Deery H
        • Embil JM
        • Joseph WS
        • Karchmer AW
        • Pinzur MS
        • Senneville E
        Clinical practice guideline for the diagnosis and treatment of diabetic foot infections.
        Clin Infect Dis. 2012; 54: 132-173
        • Gardner SE
        • Haleem A
        • Jao Y-L
        • Hillis SL
        • Femino JE
        • Phisitkul P
        • Heilmann KP
        • Lehman SM
        • Franciscus CL
        Cultures of diabetic foot ulcers without clinical signs of infection do not predict outcomes diabetes care.
        Diabetes Care. 2014; 37: 2693-2701
        • Kapur B.
        Preserving the diabetic foot—outcomes of diabetic foot ulceration and osteomyelitis treated with antibiotic loaded stimulan.
        in: British Orthopaedic Foot & Ankle Society Annual Scientific Meeting Sheffield, UK2017
        • Pierides M
        • Liarakos AL.
        Local delivery of antibiotics via highly purified calcium sulphate beads as an adjunct to surgical debridement in the acute management of diabetic foot osteomyelitis.
        in: 15th Annual Meeting of the Diabetic Foot Study Group, Berlin, Germany2018
        • Wai Chon HT
        • Hamish M
        • Kirupananthan P
        • Gmati A
        • Abdalla H
        • Hicks R.
        Stimulan® antibiotic impregnated beads for the treatment of diabetic foot infection.
        Arab J Intervent Radiol. 2020; 4: 73-78
        • Patil P
        • Singh R
        • Agarwal A
        • Wadhwa R
        • Bal A
        • Vaidya S
        Diabetic foot ulcers and osteomyelitis: use of biodegradable calcium sulfate beads impregnated with antibiotics for treatment of multi-drug resistant organisms.
        Wounds. 2021; 33: 70-78
        • Cunha BA
        Oral antibiotic therapy of serious systemic infections.
        Med Clin North Am. 2006; 90: 1197-1222
        • MacGregor RR
        • Graziani AL
        Oral administration of antibiotics: a rational alternative to the parenteral route.
        CID. 1997; 24: 457-467
      1. Turnbull C, Young L, Lowery S. Oral vs. intravenous antibiotics for the treatment of acute bacterial osteomyelitis in the veteran population open forum infectious diseases 4:1S96, 2017. Available at: Accessed June 06, 2020

        • Rausschmann M.A
        • Wichelhaus TA
        • Stirnal V
        • Dingeldein E
        • Zichner L
        • Schnettler R
        • Alt V
        Nanocrystalline hydroxyapatite and calcium sulphate as biodegradable composite carrier material for local delivery of antibiotics in bone infections.
        Biomaterials. 2005; 26: 2677-2684
        • Tiemann AH
        • Hofmann GO
        Wound irrigation within the surgical treatment of osteomyelitis.
        GMS Interdiscip Plast Reconstr Surg DGPW. 2012; 1: 1-6
        • Phyo N
        • Tang W
        • Kavarthapu V
        Medium-term outcomes of multi-disciplinary surgical management of non-ischemic diabetic heel ulcers.
        J Clin Orthop Trauma. 2021; 17: 30-36
        • Grannon P
        • Pierides M
        Evaluation: local delivery of antibiotics in elective surgery to cure chronic diabetic foot osteomyelitis and its value to antibiotic stewardship.
        in: 15th Annual Meeting of the Diabetic Foot Study Group, Berlin, Germany2018
        • Jogia RJ.
        The use of locally delivered highly purified calcium sulphate impregnated with antibiotics in the management of the diabetic foot with osteomyelitis.
        in: 15th Annual Meeting of the Diabetic Foot Study Group, Berlin, Germany2018
        • Dekker AP
        • Uzoho C
        • Scammell B.
        Do antibiotic-impregnated calcium sulfate beads improve the healing of neuropathic foot ulcers with osteomyelitis undergoing surgical debridement.
        Wounds. 2019; 31: 145-150
        • Qin C-H
        • Zhou C-H
        • Song H-J
        • Cheng G-Y
        • Zhang H-A
        • Fang J
        • Tao R.
        Infected bone resection plus adjuvant antibiotic-impregnated calcium sulfate versus infected bone resection alone in the treatment of diabetic forefoot osteomyelitis.
        BMC Musculoskelet Disorders. 2019; 20: 246
        • Tsourdi E
        • Barthel A
        • Rietzsch H
        • Reichel A
        • Bornstein SR.
        Current aspects in the pathophysiology and treatment of chronic wounds in diabetes mellitus.
        Biomed Res Int. 2013; 2013: 385641
        • Creager MA
        • Lüscher TF
        • Cosentino F
        • Beckman JA.
        Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I.
        Circulation. 2003; 108: 1527-1532
        • Trujillo J.M
        • Logue ME
        • Kunkel R
        • Demas CP.
        Off-label usage of absorbable beads containing antibiotics for prevention of surgical site infections.
        Wounds. 2017; 29: E84-E87
        • Khansa I
        • Barker JC
        • Ghatak PD
        • Sen CK
        • Gordillo GM.
        Use of antibiotic impregnated resorbable beads reduces pressure ulcer recurrence: a retrospective analysis.
        Wound Repair Regen. 2018; 26: 221-227
        • Dinh T
        • Veves A.
        The influence of gender as a risk factor in diabetic foot ulceration.
        Wounds. 2008; 20: 127-131
        • Peek ME.
        Gender differences in diabetes-related lower extremity amputations.
        Clin Orthop Relat Res. 2011; 469: 1951-1955
        • Cavanagh PR
        • Bus SA.
        Off-loading the diabetic foot for ulcer prevention and healing.
        J Vasc Surg. 2010; 52: 37s-43s
        • Rogers LC
        • Frykberg RG
        • Armstrong DG
        • Boulton AJM
        • Edmonds M
        • Van GH
        • Hartemann A
        • Game F
        • Jeffcoate W
        • Jirkovska A
        • Jude E
        • Morbach S
        • Morrison WB
        • Pinzur M
        • Pitocco D
        • Sanders L
        • Wukich DK
        • Uccioli L.
        The Charcot foot in diabetes.
        Diabetes Care. 2011; 34: 2123-2129