Osteomyelitis Treatment & Management

The principles of management of osteomyelitis necessitate a multipronged, multidisciplinary approach that may involve a team consisting of the following:

• Orthopedic surgeon
• Infectious disease consultant
• Plastic surgeon
• Microbiologist
• Others as needed

This approach should first determine whether the disease is acute, chronic, or an acute exacerbation of a chronic disease or (in some cases) a partially treated subacute osteomyelitis. Acute osteomyelitis must be treated surgically to drain pus and prevent bone necrosis. Antibiotics suited to the patient's age and the organism are given to control hematogenous spread and to treat the local infection. In other words, antibiotics save life, and surgery helps save bone.

Debridement of necrotic tissues, removal of foreign materials, and sometimes skin closure of chronic unhealed wounds are necessary in some cases.

Although vertebral osteomyelitis does not usually necessitate surgical treatment, indications include failure to respond to antimicrobial therapy, neural compression, spinal instability, or drainage of epidural or paravertebral abscesses.

The Infectious Diseases Society of America (IDSA) has published clinical practice guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults, including recommendations regarding antibiotic therapy and surgical intervention (see Guidelines). ^[42]

Antibiotic treatment should be based on the identification of pathogens from bone cultures at the time of bone biopsy or debridement. ^{[1, 4]} Bone cultures are obtained first, and suspected pathogens are then covered by initiation of a parenteral antimicrobial treatment. However, treatment may be modified once the organism is identified. Parenteral and oral antibiotics may be used alone or in combination, depending on microorganism sensitivity results, patient compliance, and infectious disease consultation.

Prophylactic treatment with the bead pouch technique has been suggested in open fractures to reduce the risk of infection. Systemic antibiotics supplemented with antibiotic beads are preferred to systemic antibiotics alone.

Local antibiotic therapy with gentamicin-impregnated Septopal beads, though available in Europe, has been controversial. ^[43]  Factors involved in the debate include the length of implantation, the need for removal, and the choice of nonabsorbable versus bioabsorbable delivery vehicles. Prolonged implantation of antibiotic beads and spacers remains controversial owing to the risk of secondary infection and development of resistant organisms. Secondary infection stems from the beads, which may serve as a foreign body upon complete elution of antibiotic.

Traditionally, antibiotic treatment of osteomyelitis has consisted of a 4- to 6-week course. ^[4] Animal studies and observations show that bone revascularization following debridement takes about 4 weeks. However, if all infected bone is removed, as in forefoot osteomyelitis, antibiotic therapy can be shortened to 10 days. ^[44]

Oral antibiotics that have been proved to be effective include clindamycin, rifampin, trimethoprim-sulfamethoxazole, and fluoroquinolones. Clindamycin is given orally after initial intravenous (IV) treatment for 1-2 weeks and has excellent bioavailability. It is active against most gram-positive bacteria, including staphylococci. Linezolid is active against methicillin-resistant staphylococci and vancomycin-resistant Enterococcus. It inhibits bacterial protein synthesis, has excellent bone penetration, and is administered IV or orally.

Oral quinolones are often used in adults for gram-negative organisms. Quinolones have excellent oral absorption and may be used as soon as patient is able to take them. Rifampin has an optimal intercellular concentration and a good sensitivity profile for methicillin-resistant staphylococci. It is used in combination with cell wall–active antibiotics to achieve synergistic killing and to avoid rapid emergence of resistant strains.

Empiric therapy is necessary when it is not possible to isolate organisms from the infection site. ^[1] Hospital-acquired infections are usually derived from methicillin-resistant staphylococci. Infections contracted outside the hospital are often polymicrobial with the presence of gram-negative bacteria.

Infection may fail to improve, owing to the ability of bacteria to resist antibiotics. Some bacteria, such as S epidermidis in prosthesis infections, adhere to a biofilm that protects the organism from phagocytosis and impedes delivery of the antibiotic. The use of rifampin in combination with other antibiotics has been found to be more effective than monotherapy for treating infection associated with surgical hardware. ^{[1, 45]}

Suppressive antibiotic therapy should also be directed by bone culture and is given orally when surgery is contraindicated. ^[4] Good bioavailability, low toxicity, and adequate bone penetration are important factors in treatment. If the infection recurs after 6 months of suppressive antibiotic treatment, a new lifelong regimen of suppressive therapy may be tried.

Extensive studies of suppressive therapy with administration of rifampin, ofloxacin, fusidic acid, and trimethoprim-sulfamethoxazole for 6-9 months have been performed in patients with infected orthopedic implants. Studies have shown that, after discontinuance of antibiotics, no recurrence of infection occurred in 67% of patients treated with trimethoprim-sulfamethoxazole, 55% of patients treated with rifampin and fusidic acid, and 50% of patients treated with rifampin and ofloxacin. ^[4]

The Ilizarov technique is usually well tolerated by the patient, with little associated pain. A few complications that have been reported include pin-tract infections and cellulitis, flexion contractures above and below the frame, limb edema, and bone-fragment rotation with malunion. ^[46]

During the course of treatment with the Ilizarov technique, patients have a high emotional and physical burdens. However, these symptoms improve, and patients are similar to the general population postoperatively. Appropriate patient counseling regarding the psychological impact of this treatment is needed. ^[47]

The complication rate may be decreased by future efforts to improve the Ilizarov method. ^[48]  Some goals include improving the technique to prevent pin-track infections and osteomyelitis, premature or delayed consolidation of bone, angular or axial deviation of the new bone, joint contracture or instability, neurovascular compromise, and psychological adjustment reactions.

Preoperative planning

The Cierny-Mader classification system (see Workup) plays an important role in guiding treatment. As noted, stage 1 and 2 disease usually do not require surgical treatment, whereas stage 3 and 4 respond well to surgical treatment. In Cierny-Mader class C hosts, treatment may be more harmful than the osteomyelitis itself. ^[9]

Operative treatment consists of the following ^[4] :

• Adequate drainage
• Extensive debridement of necrotic tissue
• Management of dead space
• Adequate soft-tissue coverage
• Restoration of blood supply

When a fracture and stable hardware are involved, surgery is used to treat a residual infection after suppressing the infection until the fracture heals. Techniques involve second-stage hardware removal followed by treatment of an infected nonunion, often with an external fixator. External fixators, plates, screws, and rods may be used to restore skeletal stability at the infection site. ^[4] Because hardware tends to become secondarily infected, external fixation is preferred to internal fixation.

Remission or cure is most likely with extensive debridement, obliteration of dead space, removal of any hardware, and appropriate antibiotic therapy.

Debridement of all nonviable or infected tissue is critical because retained necrotic or infected debris can result in osteomyelitis recurrence. Bone debridement is performed until punctuate bleeding is noted. ^[4] The remaining tissue is still considered contaminated even after adequate debridement of necrotic tissue. Studies have shown that marginal resection may be sufficient in normal hosts. However, in compromised hosts, extensive resection seems to be much more important.

The term dead space refers to the soft-tissue and bony defect left behind after debridement. ^[4] Appropriate management of this space is necessary to reduce the risk of persistent infection from poor vascularization of the area and to maintain the integrity of the skeletal part.

Dead space must be filled with durable vascularized tissue, sometimes from the fibula or ilium. Antibiotic-impregnated beads may be used for temporary sterilization of dead space. Vancomycin, tobramycin, and gentamicin are some of the common antibiotics used in these beads. Within 2-4 weeks, the beads may be replaced with cancellous bone graft.

Because two major aims of surgical treatment are resection of necrotic bone and thorough debridement of intraosseous and soft-tissue fistula, computed tomography (CT) is sometimes performed for the purpose of planning a surgical intervention and guiding surgery. Preoperatively, CT is helpful for characterizing bone quality, demonstrating intraosseous fistula, and detecting devitalized bone areas or cortical defects that lead to soft-tissue sinus tracts. ^[2]

When osteomyelitis involves a fracture, it is also important to include a workup to be sure the fracture has healed. Antibiotic-impregnated beads may be used as an effective measure to maintain sterile dead space until a definitive surgical procedure can be performed.

In order to apply the Ilizarov method successfully and to prevent damage to vital nerves and blood vessels, preoperative planning is helpful, with careful attention to "safe zones" during wire insertion. It is important to adjust the skin to prevent tension on the skin-wire interface. Correction of the deformity or lengthening is better achieved by appropriately constructing the Ilizarov frame. ^[49]

Antibiotic-impregnated ceramics

Given that a central tenet in surgical management of osteomyelitis involves filling in the dead space with viable vascularized tissue, it is not surprising that various ways of filling the defect and maximizing local antibiotic delivery have been engineered (eg, use of antibiotic-impregnated cements). Antibiotic-impregnated polymethylmethacrylate (PMMA) cement can provide sustained therapeutic concentrations of antibiotics locally in treatment and prophylaxis of osteomyelitis and has been widely used in clinical practice for 40 years. ^[50] This method relies on local diffusion and depends on the surface area of the cement and the concentration gradient between the cement and the local tissues. ^[51]

A retrospective cohort study of 501 shoulders showed that antibiotic-impregnated PMMA cement was effective in reducing deep infection for primary reverse total shoulder arthroplasty. ^[52] Nevertheless, PMMA cement has several drawbacks: it undergoes a thermogenic reaction that can degrade impregnated antibiotics, it loses structural integrity with high concentrations of antibiotic, and the dose of locally administered antibiotic is high in the first 24-72 hours but falls steeply to lower levels thereafter. Furthermore, PMMA is not biodegradable, and a second surgical procedure must be performed to remove to remove the implants once the infection has been treated.  

To address this issue, exploration into biodegradable inorganic ceramic materials has yielded developments in ceramic antibiotic carriers—principally, calcium phosphate cement (CPC) materials and calcium sulfate–based materials. These biomaterials, which have chemical and crystal properties similar to those of bone, may promote osteoconduction and osteogenesis and have been used to repair bone defects. ^{[50, 53]}  In addition, they are biodegradable and thus do not have to be removed with a second surgical procedure after placement.

CPC impregnated with antibiotics can release locally therapeutic amounts of antibiotics over long periods. ^{[54, 55, 56]}  Studies comparing the release efficacy of vancomycin from CPC with that from PMMA have demonstrated that CPC can release more antibiotics than PMMA because it does not undergo a thermogenic reaction, which can cause the molecule to undergo thermal degradation. ^{[57, 58]}

The most commonly used commercially available antibiotic ceramic carriers are the following ^[59] :

• Osteoset T - α-Hemihydrate calcium sulphate pellets, with tobramycin
• Herafill G - Calcium sulphate and carbonate pellets, with gentamicin
• Cerament G and Cerament V - Biphasic paste mix of calcium sulphate and nanocrystalline hydroxyapatite, with gentamicin (G) or vancomycin (V)

To date, there have been few high-powered studies investigating the outcomes in humans treated for osteomyelitis with these compounds. In a prospective study of 100 patients with chronic osteomyelitis who were treated with standard care plus a gentamicin-loaded calcium sulfate–hydroxyapatite biocomposite into the dead space, 96 patients were successfully treated with a single surgical procedure; the other four were successfully treated with a subsequent surgical procedure. ^{[60, 61]}

Bone transport (Ilizarov method)

The Ilizarov method, developed by Ilizarov in 1951, promotes bone growth through distraction osteogenesis using a specialized device and systematic approach. This technique has facilitated limb-lengthening, reduced the incidence of many complications, and decreased the level of surgical intervention necessary.

The Ilizarov method involves the use of a tissue-sparing cortical osteotomy-osteoclasis technique that preserves the osteogenic elements in the limb. To create a preliminary callus that can be lengthened, Ilizarov advocated a delay of several days before distraction is initiated. A high-frequency, small-step distraction rhythm permits regeneration of good-quality bone and leads to fewer soft-tissue complications (eg, nerve and vessel injury). It utilizes the concept of "tension stress," in which gradual distraction stimulates bone production and neogenesis.

The Ilizarov device is attached to the distal or proximal portion of the affected bone. Bone regenerates as the screw and wire mechanism moves the healthy bone fragment at a maximal rate of approximately 0.25 mm four times per day for an overall rate of 1 mm/day. An advantage of using this procedure is that it minimizes the prevalence of nonunion and thus further bone grafting by producing good-quality bone formation.

The risk of repeat osteotomy and osteoclasis is also decreased, owing to less premature consolidation of the lengthened segment. ^[48] However, Ilizarov techniques are often not tolerated well by patients, and other options, including amputation, may be preferred.

The Ilizarov external fixator is a popular device that is composed of wires, fixation bolts, rings, threaded rods, hinges, and plates, together allowing customized assemblies. Although this apparatus is stiff for bending and torsion, it is less stiff for axial loading. This feature is thought to help promote osteogenesis. ^[49]

Nonunions, malunions, or defects of any length can be treated and may also be corrected by using the Ilizarov method. At the same time, the Ilizarov technique is labor-intensive and may require at least 8 months of treatment. In addition, the fixator pins can be uncomfortable and often become infected. Amputation is an option if reconstruction is not suitable.

After a corticotomy is made for bone lengthening, a latency period is required before distraction. Once distraction has begun, new bone should be apparent within 3-4 weeks. After the appropriate length is obtained or the angular deformity corrected, the apparatus remains in place until completion of the consolidation phase. During the postoperative period, it is necessary to adjust or modify the assembly, and the apparatus is removed when the goal is achieved. ^[49]

Because the apparatus may be in place for an extended period, even as long as 1 year, special postoperative considerations are important. ^[49]  Pain management may be a challenge because of the duration of mild-to-moderate postoperative pain. For preventing flexion contractures of the surrounding joints, intensive physical therapy and splinting techniques are key elements. Successful treatment also requires psychological support and family counseling.

Problems to be particularly watchful for during the postoperative period include pin-track infections, premature or delayed consolidation, joint contractures, and pin breakage that may require replacement.

Imaging studies in the follow-up period are most useful in patients who have equivocal or worse clinical status at the end of therapy.

Management of critical bone defect

Debridement of all nonviable or infected tissue is critical because retained necrotic or infected debris can result in recurrence of osteomyelitis. Bone debridement is typically performed until punctuate bleeding is noted. ^[4]  In this process, a bone defect is often left to be dealt with. A so-called critical bone defect is one that will not heal without additional surgical intervention. Typically, a segmental bone deficit of a length exceeding 2 to 2.5 times the diameter of the affected bone is considered a critical bone defect. ^[62]

Induced membrane (Masquelet) technique

The induced membrane technique (Masquelet technique) is a two-stage procedure that requires a robust preoperative assessment of the patient and planning of the surgical procedures. The steps of the method along with the specific technical details have been well described. ^[63]  Although retrospective in nature, all of the studies on the use of this technique have reported favorable outcomes. ^{[64, 65, 66]}

The only prospective study to date, by Cho et al, ^[67]  included 21 patients who were treated with the Masquelet technique. The patients had critical-size defects located at the metadiaphyseal area of 11 tibias, eight femurs, and two humeri, averaging  8.9 cm in length and 65.2 cm³ in volume. Eighteen patients (86%) were healed radiographically at an average of 9.1 months.

Nonvascularized bone graft

Nonvascularized bone grafts can be used for reconstruction of large segmental defects but require at least 4 to 8 weeks for revascularization. Most cells in autogenous grafts do not survive the transplantation and must be replaced and repaired by using new bone in a process called creeping substitution. It is likely that the graft is never completely replaced by healthy bone; the result is a mixture of necrotic and viable bone. Accordingly, autogenous nonvascularized bone graft is indicated only for filling bone defects smaller than 6 cm, in the setting of adequate soft-tissue coverage.

The disadvantages are infection of the wire site, docking-site nonunion, and prolonged use of the external fixator.

Vascularized bone graft

Vascularized bone grafts are indicated when the skeletal defect is longer than 6 cm. ^[68]  They combine the viability of cancellous grafts with the stability of cortical analogues while leaving their nutrient blood supplies intact. Their use can achieve the following goals:

• Obliterate the dead space
• Bridge the large bone defect
• Enhance bone healing
• Resist infection (with increased blood supply)
• Allow early rehabilitation
• Ensure better clinical outcomes

The reported success rates for microsurgical flap transfer for osteomyelitis treatment has ranged from 80% to 95%. ^[68]

Suction irrigation system

The Lautenbach system, using a closed double-lumen tube delivering antibiotic locally, followed by suction, has previously been used in the treatment of infected hip replacements. ^[69]

Hashmi et al ^[70] described a series of 17 patients with posttraumatic osteomyelitis who were treated by this method and achieved a 94.4% infection clearance rate after a mean follow-up of 75 months. All patients remained infection-free for the duration of the study.

Wound closure

To arrest infection, it is necessary to provide adequate soft-tissue coverage. ^[4] Over small soft-tissue defects, a split-thickness skin graft may be placed, whereas large soft-tissue defects may be covered with local muscle flaps and free vascularized muscle flaps. Rotation of a local muscle with its neurovascular supply must be possible anatomically for that procedure to be successful.

These flaps bring in a blood supply, which is important for host defense mechanisms, new bone regeneration, delivery of antibiotics, and healing. They also may be used in combination with antibiotics and surgical debridement of necrotic and infected tissues. The fibula and iliac crest are common donor sites for free flaps.

Hydrocolloid wound dressings

Hydrocolloid dressings form an occlusive barrier over the wound while maintaining a moist wound environment and preventing bacterial contamination. A gel is formed when wound exudate comes in contact with the dressing. This gel can have fibrillolytic properties that enhance wound healing, protect against secondary infection, and insulate the wound from contaminants. Hydrocolloids help prevent friction and shear and may be used in stage 1, 2, 3, and some stage 4 pressure injuries with minimal exudate and no necrotic tissue. ^[71]

Negative-pressure wound therapy

Negative-pressure wound therapy (NPWT) has increasingly become a popular treatment for the management of both acute and chronic wounds. Its use in orthopedics is diverse and includes the acute traumatic setting, as well as chronic wounds associated with pressure injuries and diabetic foot surgery.

The theoretical basis for the use of NPWT is that the local factors at the wound bed can have a negative effect on the wound-healing process. The presence of infection, local edema, high-flowing exudates, and ischemia can delay the healing process. NPWT is thought to reduce these negative effects via the following mechanisms ^[72] :

• Promoting a lower bacterial count
• Increasing vascularity and cell proliferation
• Promoting removal of exudate from the wound
• Promoting granulation tissue and encouraging the wound edges to come together

In the case of acute open traumatic wounds, NPWT may be used to facilitate delayed primary closure, promote secondary healing by granulation, or prepare for subsequent placement of a graft or flap.

Lee et al reported on the use of NPWT in 16 patients with severe open traumatic wounds of the foot and ankle. ^[73] Before applying NPWT, the authors irrigated and debrided necrotic and contaminated tissue and fixated fractures, if present. Negative pressure was applied continuously at 100-125 mm Hg. The mean reduction in wound size was 24%. In 15 patients, the wound bed granulated sufficiently to allow application of a split-thickness skin graft for closure; one patient required a free flap. There were no major complications and only two minor complications of skin-graft contracture.

NPWT may preserve limbs in patients with diabetic or neuropathic foot ulcers by diminishing their size to allow subsequent coverage procedures. In a meta-analysis (eight studies; N = 669) aimed at determining the efficacy and safety of NPWT for diabetic foot ulcers, ^[74] Zhang et al found that NPWT, compared with treatment without NPWT, had a relative risk (RR) of 1.52 for healing, a greater reduction in the area of the ulcer, and a shorter time to healing (mean difference, −1.1 months). NPWT resulted in significantly fewer major amputations, but there was no significant difference in the rate of minor amputations.

Adjunctive hyperbaric oxygen therapy

Adjunctive hyperbaric oxygen therapy (HBOT) can promote collagen production, angiogenesis, and healing in an ischemic or infected wound. ^[4]

Adults 

In patients without retained hardware, a course of IV antibiotics for at least 6 weeks is recommended, with weekly blood chemistries and inflammatory markers (including erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]) at the beginning and end of antibiotic therapy to monitor for recurrence. ^[75]

For patients with retained hardware, an extended course of antibiotics is recommended for at least 6 weeks. Follow-up involves monitoring of blood chemistries weekly and inflammatory markers (including ESR and CRP) at the beginning and end of therapy and during the transition from IV to oral antibiotics. For patients with retained hardware or necrotic bone not amenable to debridement, oral antibiotics should be administered for an extended period for suppression. While the patient is on oral antibiotics, blood chemistries and inflammatory markers are checked at 2, 4, 8, and 12 weeks and 6 and 12 months. ^{[76, 77, 78]}

Children 

Follow-up for children with osteomyelitis is similar to that for adults. Antimicrobial therapy is initiated for a minimum of 4 weeks, typically starting with IV antibiotics and then bridging to oral antibiotics as systemic symptoms (eg, fever and leukocytosis) resolve. Before therapy has been completed, ESR and CRP are checked, and antimicrobial therapy is maintained if there are any elevations. Radiographs are commonly obtained as well to evaluate for bony lesions.

In chronic osteomyelitis, IV therapy for 2-6 weeks, followed by oral antibiotics for a total of 4-8 weeks, may be required. Prolonged courses may be required in neonates, immunocompromised or malnourished patients, patients with sickle cell disease, and patients with distant foci of infection (eg, endocarditis). ^{[75, 79, 80, 81, 82]}