Table 6.

Description of the treatment strategies reported by all included studies

Study	Treatment
Beals 200518	4 treatment patterns: 8 patients received local debridement with or without soft tissue coverage, 3 radical debridement and bone transport using circular frame, 8 treated by Papineau grafting technique post debridement, 11 received debridement and circular frame fixation. All patients received 6 months targeted IV antibiotics.
Chan 199819	Stage 1: debridement, sequestrectomy and removal of metalwork with implantation of targeted antibiotic-impregnated poly(methyl methacrylate) bead chains. Stage 2: 2 – 10 weeks later, bead removal and targeted antibiotic-coated cancellous bone graft from anterior iliac crest. All patients received one week of post-operative intravenous antibiotic therapy.
Chan 2000 20	Staged antibiotic-impregnated autogenous cancellous bone graft (46 patients) or pure autogenous cancellous bone graft (50 patients).
Chang 200721	Group 1: debridement and targeted systemic antibiotic therapy only (40 patients). Group 2: debridement with insertion of tobramycin OSTEOSET- T® pellets and targeted systemic antibiotic therapy.
Chen 200410	Debridement followed by a course of hyperbaric oxygen therapy. The compression chamber used 100% oxygen delivered via a mask system with 2.5 atmospheres absolute for 2-hour duration with intermittent schedule of 25 minutes of 100% oxygen breathing and 5 minutes air breathing, 1 session per day, 5 days per week. Additional debridement followed if necessary; 11 patients also received cancellous bone grafting. All patients received 2 weeks targeted IV antibiotic, followed by 2–4 weeks oral antibiotic therapy.
Emara 200222	Debridement followed by hemi-corticotomy. Ilizarov external fixation frame then applied; Orthofix limb reconstruction external fixation system used. All patients given two weeks targeted antibiotic therapy post-operatively.
Euba 200923	Group 1: debridement with 6 weeks IV (2 g/4 h) then 2 weeks oral (500 mg/6 h) cloxacillin (22 patients). Group 2: debridement with rifampicin-cotrimoxazole (600 mg rifampicin/24 h + 7/8 mg/kg body weight/day cotrimoxazole) (28 patients). Surgery included extensive debridement of bone and soft tissue, removal of foreign material. Closed suction irrigation or muscular flap complemented debridement when indicated.
Ferguson 201424	Debridement with insertion of tobramycin OSTEOSET-T® pellets and targeted systemic antibiotic therapy.
Ferrando 201725	Group 1: surgical debridement, systemic antibiotics and local application of bioactive glass S53P4 (12 patients). Group 2: surgical debridement, systemic antibiotics and local application of calcium sulphate antibiotic beads with a combination of vancomycin and gentamycin (13 patients). All patients received 6–12 weeks of antibiotic therapy.
Fitzgerald 198526	Debridement/sequestrectomy and application of a local muscle flap. A soleus or gastrocnemius muscle flap was most frequently utilized to achieve closure. In 5 patients, combination of 2 muscle flaps was utilized. Multiple debridements performed in 28/42 patients. All patients received targeted IV antibiotic therapy, for a mean duration of 24 days following surgery.
Hashmi 200427	Lautenbach procedure – radical debridement and reaming with insertion of double lumen local antibiotic system with targeted systemic antibiotics.
Huang 201828	Autoplastic transplantation of ilium to eliminate sequestrum and inflammatory granuloma (all patients). Control group (40 patients): targeted antibiotic therapy, no treatment length recorded. Observation group (40 patients): antibiotic therapy and Chinese medicinal wuwei xiadou drink.
Jiang 201529	Radical debridement followed by IV antibiotic therapy and reconstruction of bone/soft tissue if necessary. Median duration of IV antibiotic treatment was 14 days.
Kelly 199030	Stage 1: soft tissue and bone debridement until bleeding tissue encountered. Chronically infected skin, soft tissue and muscle also excised. Stage 2: wound closure and coverage of saucerized osseous cavity by delayed closure muscle flap, free-tissue transfer and skin graft with suction drainage/irrigation. Bone grafts used in cases of nonunion. At least 4 weeks targeted IV antimicrobial therapy.
Khan 201231	Radical debridement and stabilization of fracture with open reduction and internal fixation (5 patients) or external fixation with Hoffman frame/hybrid ring/Braun frame (15 patients). Local flap skin grafts for soft tissue cover, taken from radial forearm. Detail regarding any antibiotic therapy not available.
Kinik 200832	Debridement with saline irrigation and insertion of vancomycin poly(methyl methacrylate) beads and targeted systemic antibiotic therapy.
Koval 199233	All patients received debridement and osseous stabilization if needed. Soft tissue management was divided into 3 groups: Group 1 (15): free or rotational muscle flap coverage. Group 2 (11): suction irrigation primary closure. Group 3 (5): Papineau technique of open cancellous bone grafting. All patients received antibiotic therapy for an average of 39.2 days (range 5–84 days).
Lam 201934	Stage 1: debridement – single (21 patients), multiple 46. 14 patients received local antibiotic-loaded beads and 10 patients received poly(methyl methacrylate)-coated intramedullary nails. Stage 2: limb salvage and soft tissue coverage using free tissue transfer. Stage 3: IV/PO antibiotics for 6 weeks in all patients, and average of 2.7 months of additional daily antibiotics for infected nonunion cases (54 patients).
Lê Thua 201535	Drainage, extensive debridement, reduction of dead space, soft tissue coverage and antibiotic therapy for 4-6 weeks. When the clinical absence of infection was confirmed by microbiological testing, open bone was irrigated with saline solution for 2 weeks, followed by free muscle transfer. Muscle flaps included latissimus dorsi, gracilis and rectus abdominis muscles depending on the location, size and length of dead bone.
Li 201936	Debridement with external fixation of the tibia and vacuum seal drainage. Antibiotic bone cement consisting of vancomycin-loaded poly(methyl methacrylate) inserted into defect. Post-operative antibiotic treatment for 6 weeks.
Lidgren 198037	Intramedullary reaming in all. Closed intramedullary suction irrigation drainage daily for 5 days (9 patients). Gentamycin-poly(methyl methacrylate) beads were implanted into marrow cavity (5 patients). Post-operative targeted antibiotics were administered perorally for average of 10 months, according to pattern of resistance.
Lindfors 2017 38	Group 1 (98 patients) – 1-stage procedure: debridement followed by filling of cavitary defect with bag-S53P4. Group 2 (18 patients) – 2-stage procedure: debridement with implantation of Septopal antibiotic beads. Second stage performed 1–4 months later, at which time the beads were removed, and defect filled with bag-S53P4. Muscles flaps used in 15 patients, and skin transplantation performed in 3 patients. All patients received systemic antibiotics (unknown period).
Marais 201639	Marginal or wide resection, dead-space management, provision of bony stability, soft tissue reconstruction, and/or skeletal reconstruction. Post-operatively, all patients were treated with IV cefazolin and imipenem until microscopy culture and sensitivity results became available. Following this, patients received targeted oral antibiotic therapy for 6 weeks.
McNally 199340	Belfast technique: Stage 1 – radical debridement with dead-space elimination using either muscle flap transfer, direct skin closure with implantation of gentamycin loaded poly(methyl methacrylate) beads or composite flaps from deep circumflex iliac artery. At least 2 antibiotics were given before surgery, these antibiotics were continued with oral preparations of the chosen drug. Stage 2 – autogenous bone grafting, carried out between 3–6 weeks after stage 1 when soft tissues had adequately healed. 5 patients did not have 2nd stage to their treatment. Antibiotics were continued until there was radiological and clinical evidence of union.
McNally 201641	Debridement with insertion of gentamycin-infused CERAMENT G® (Bonesupport, Lund, Switzerland) and targeted systemic antibiotic therapy.
Meissner 198942	Debridement with adjuvant IV Fosfomycin therapy. Fosfomycin therapy was withdrawn around 3 days after confirmed reduction in inflammatory parameters.
Pape 199543	Reaming of intramedullary canal in all. 13/32 patients received poly(methyl methacrylate) chains after reaming, 3 received instillation drainage. No data regarding antibiotic therapy recorded.
Patzakis 199344	Randomized Septopal-gentamicin group (17 patients) of which 12 in Septopal arm, 5 in antibiotic arm. Remainder (16) in non-randomized group. Septopal patients (12 patients): systemic antibiotic therapy. Antibiotic arm (5 patients): 4–6 weeks of IV antibiotic therapy followed by 3 months of oral antibiotic therapy. Non-randomized group (16): 3–4 weeks of IV antibiotic therapy followed by oral antibiotic therapy. Randomized group received primary closure of wounds or soft tissue muscle transfer at time of debridement. Non-randomized group received initial debridement with muscle transfer 3–9 days later.
Romanò 201445	Group 1: debridement and application of S53P4 bioactive glass, no local antibiotics (27 patients). Group 2: debridement and targeted antibiotic-loaded hydroxyapatite and calcium sulphate (27 patients). Group 3: debridement and teicoplanin-loaded demineralized bone matrix (22 patients). All groups received 4–12 weeks teicoplanin. Debridement involved removal of all foreign materials, bone substitutes and macroscopically infected/necrotic tissues and debridement of medullary canal followed by repeated lavage with saline. Post-operatively, all groups received 4–12 weeks of systemic antibiotic therapy, determined by prior consultation with infectious diseases specialist and microbiology department. A combination of targeted 2 antibiotics usually administered or if cultures were negative, vancomycin or teicoplanin and meropenem for 14 days followed by oral levofloxacin and rifampicin.
Sachs 198446	3-stage Papineau protocol. Oral antibiotics were continued until each wound had complete skin coverage.
Sen 201947	Stage 1: radical bone resection and soft tissue debridement, with implantation of antibiotic-coated beads and targeted intravenous antibiotic therapy. Stage 2: acute shortening and re-lengthening osteotomy (17 patients) or segmental bone transport with a 4-ring Ilizarov frame (15 patients). In all cases, targeted IV antibiotics were administrated for a minimum of 6 weeks, or until CRP and ESR levels had returned to normal.
Shen 201548	Debridement and vacuum sealing drainage after which culture and sensitivity testing performed. 2nd debridement with internal fixation device removed if not contributing to stability of bone. External fixation added if unstable fracture present. Defect packed with calcium sulphate beads impregnated with vancomycin 1 g. If debridement cavity was large and autograft was used to fill the residual space. Systemic targeted antibiotics administered for 2–4 weeks.
Siegel 2000 49	Limb salvage, including extensive debridement, autogenous bone grafting, and soft tissue reconstruction and flap coverage (30 free flaps, 16 rotational flaps). All patients were treated with local and systemic antibiotics under the supervision of an infectious-disease specialist. Duration of treatment not provided.
Simpson 200150	Group 1: wide excision > 5 mm margin (15 patients). All necrotic and infected bone was excised, remaining bone was clearly viable with good punctate bleeding. Group 2: marginal excision < 5 mm margin (29 patients). All necrotic and infected bone was excised but with smaller margin of clearance. Group 3: intralesional biopsy with pus drainage, lavage and debulking (6 patients). Broad-spectrum IV antibiotics administered to all patients, later modified after results from cultures and sensitivity assessment were obtained and continued for 6 weeks. Patients then switched to 6 weeks oral antibiotic therapy.
Smith 200651	Wide excision of affected soft and hard tissue. Involucrum fenestrated and necrotic bone sequestra excised. Suction drain placed in remaining gutter. Dead space obliterated with free muscle transfer. IV ciprofloxacin given at time of surgery and then orally for 6 weeks post-operatively. If microbiology culture and sensitivity suggested another more appropriate antibiotic, targeted antibiotics were given.
Sun 201852	Experimental group (36 patients): debridement with insertion of gentamycin-impregnated beads, drainage and wound closure. IV antibiotics administered to all patients (unknown period). Control group (36): removal of necrotic and infected tissue with lavage/drainage. Daily local rinsing with gentamycin dissolved in saline. All patients received targeted IV antibiotic therapy.
Wang 201753	Induced membrane 2-stage surgical technique, Stage 1: radical debridement followed by insertion of antibiotic-loaded poly(methyl methacrylate). Targeted IV antibiotics administered for 2 weeks post-operatively. Stage 2 occurred 6–8 weeks later: bone graft implantation to repair defects after 6–8 weeks, prophylactic antibiotics administered for 24 hours and suction drainage applied for 10–12 days.
Yamashita 199854	Debridement with insertion of gentamycin/imipenem calcium hydroxyapatite implants and systemic targeted antibiotic therapy.
Zhou 202055	Fenestration and debridement with placement of vancomycin/gentamycin-loaded calcium sulphate. Broad-spectrum antibiotics administered post-operatively, later switched to targeted therapy for no more than 2 weeks.
Zweifel-Schlatter 200656	Radical bone excision and, if necessary, further stabilization of the tibia carried out followed by microvascular transfer of fasciocutaneous flap after 7–10 days. Targeted antibiotic treatment started from time of definitive coverage with free fasciocutaneous flap and continued for 3–6 months post-operatively.

Note. IV, intravenous; PO, per os (by mouth) ; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate.