Thursday, January 21, 2010

CHRONIC OSTEOMYELITIS

Bookmark and Share




CHRONIC OSTEOMYELITIS
Chronic osteomyelitis is difficult to eradicate completely. Systemic symptoms may subside, but one or more foci in the bone may contain purulent material, infected granulation tissue, or a sequestrum (Fig. 16-10). Intermittent acute exacerbations may occur for years and often respond to rest and antibiotics. The hallmark of chronic osteomyelitis is infected dead bone within a compromised soft-tissue envelope. The infected foci within the bone are surrounded by sclerotic, relatively avascular bone covered by a thickened periosteum and scarred muscle and subcutaneous tissue. This avascular envelope of scar tissue leaves systemic antibiotics essentially ineffective.

In chronic osteomyelitis, secondary infections are common, and sinus track cultures usually do not correlate with cultures obtained at bone biopsy. Multiple organisms may grow from cultures taken from sinus tracks and from open biopsy specimens of surrounding soft tissue and bone.                                                                                                                                                           Eradication of chronic osteomyelitis generally requires aggressive surgical excision combined with effective antibiotic treatment. Surgery is not always the best option, however, especially in compromised patients. Consider an ambulatory immunocompromised host with multiple medical problems, including chronic osteomyelitis of the femur. For this patient, who might not survive the extensive surgical stress required to eradicate the disease, less aggressive alternatives should be considered. Limited surgical débridement combined with suppressive antibiotics and nutritional support may limit the frequency of sinus drainage and pain in these difficult cases. The treatment course and definition of outcome success must be individualized for each patient.

Classification
Cierny and Mader developed a classification system for chronic osteomyelitis, based on physiological and anatomical criteria, to determine the stage of infection. The physiological criteria are divided into three classes based on three types of hosts. Class A hosts have a normal response to infection and surgery. Class B hosts are compromised and have deficient wound healing capabilities. When the results of treatment are potentially more damaging than the presenting condition, the patient is considered a class C host.
Anatomical criteria consist of four types. Type I, a medullary lesion, is characterized by endosteal disease. In type II, superficial osteomyelitis is limited to the surface of the bone, and infection is secondary to a coverage defect. Type III is a localized infection involving a stable, well-demarcated lesion characterized by full-thickness cortical sequestration and cavitation (in this type, complete débridement of the area would not lead to instability). Type IV is a diffuse osteomyelitic lesion that creates mechanical instability, either at presentation or after appropriate treatment (Table 16-2 and Fig. 16-11).

Table  --  Cierny and Mader Staging System for Chronic Osteomyelitis

Anatomical Type
I
Medullary
Endosteal disease
II
Superficial
Cortical surface infected because of coverage defect
III
Localized
Cortical sequestrum that can be excised without compromising stability
IV
Diffuse
Features of I, II, and III plus mechanical instability before or after débridement
Physiological Class
A host
Normal
Immunocompetent with good local vascularity
B host
Compromised
Local (B) or systemic (S) factors that compromise immunity or healing
C host
Prohibitive
Minimal disability, prohibitive morbidity anticipated, or poor prognosis for cure
The anatomical and physiological classes are combined to designate one of 12 clinical stages of chronic osteomyelitis. A type II lesion in a class A host is designated stage IIA osteomyelitis. This classification system is helpful in determining if treatment should be simple or complex, curative or palliative, and limb sparing or ablative.
Diagnosis
The diagnosis of chronic osteomyelitis is based on clinical, laboratory, and imaging studies. The “gold standard” is to obtain a biopsy specimen for histological and microbiological evaluation of the infected bone.
Physical examination should focus on the integrity of the skin and soft tissue, determine areas of tenderness, assess bone stability, and evaluate the neurovascular status of the limb. Laboratory studies generally are nonspecific and give no indication of the severity of the infection. ESR and C-reactive protein are elevated in most patients, but the white blood cell count is elevated in only 35%.

Imaging studies for confirmation of the diagnosis and to prepare for surgical treatment. Plain radiographs is initial study performed. Signs of cortical destruction and periosteal reaction strongly suggest the diagnosis of osteomyelitis. Plain tomography is not as readily available as it was previously; however, if it can be obtained, it is extremely useful in the detection of sequestra. Sinography can be performed if a sinus track is present and can be a valuable adjunct to surgical planning 
Isotopic bone scanning is more useful in acute osteomyelitis than in the chronic form because the former typically has negative plain films. Indium-111–labeled leukocyte scans are more sensitive than technetium or gallium scans and are especially useful in differentiating chronic osteomyelitis from neuropathic arthropathy in the diabetic foot.

CT provides excellent definition of cortical bone and a fair evaluation of the surrounding soft tissues and is especially useful in identifying sequestra. MRI is more useful for soft-tissue evaluation than CT. MRI provides a fairly accurate determination of the extent of the pathological insult by showing the margins of bone and soft-tissue edema. MRI was found to be much more sensitive than the nuclear studies.

In chronic osteomyelitis, MRI may reveal a well-defined rim of high signal intensity surrounding the focus of active disease (rim sign). Sinus tracks and cellulitis appear as areas of increased signal intensity on T2-weighted imaging. As previously noted, the “gold standard” in the diagnosis of osteomyelitis is a biopsy with culture and sensitivity. A biopsy is not only useful in establishing a diagnosis, but also is helpful in determining the proper antibiotic regimen. Typically, staphylococcal species are identified, especially in posttraumatic infections. Anaerobes and gram-negative bacilli are commonly isolated.

Treatment
Chronic osteomyelitis generally cannot be eradicated without surgical treatment. Antibiotics alone rarely can eradicate the infection for numerous reasons. Bacteria are able to adhere to orthopaedic implants and bone matrix through various receptors. Some can hide intracellularly. Others can form a slimy coat that protects them from phagocytic cells and antibiotics.
Surgery for chronic osteomyelitis consists of sequestrectomy and resection of scarred and infected bone and soft tissue. The goal of surgery is eradication of the infection by achieving a viable and vascular environment. Radical débridement may be required to achieve this goal. Inadequate débridement may be one reason for a high recurrence rate in chronic osteomyelitis.

No recurrences in the group treated with wide resection (>5 mm), whereas patients treated with marginal resection (<5 mm) had a 28% recurrence rate. Adequate débridement often leaves a large dead space that must be managed to prevent recurrence and significant bone loss that may result in bony instability. Reconstruction done such as skin grafts, muscle and myocutaneous flaps, and occasionally free flaps (Fig. 16-13). The duration of postoperative antibiotics is controversial. 6-week course of intravenous antibiotics is prescribed after surgical débridement of chronic osteomyelitis, followed by clinical and laboratory examinations.

Sequestrectomy and Curettage for Chronic Osteomyelitis
Sinus tracks can be injected with methylene blue 24 hours before surgery to make them easier to locate and excise.
TECHNIQUE  
•    Expose the infected area of bone and excise all sinus tracks completely.
    Incise the indurated periosteum and elevate it 1.3 to 2.5 cm on each side.
    Use a drill to outline a cortical window at the appropriate site and remove it with an osteotome.
    Remove all sequestra purulent material and scarred and necrotic tissue (Fig. 16-14A and B). If sclerotic bone seals off a cavity within the medullary canal
open it into the canal in both directions to allow blood vessels to grow into the cavity. A high-speed burr helps to locate the demarcation between healthy and ischemic bone.
    After removing all suspicious matter carefully excise the overhanging edges of bone and avoid leaving a cavity or dead space. If a cavity cannot be filled by the surrounding soft tissue a local muscle flap or a free tissue transfer can be used to obliterate the dead space.
    If there is a nonunion present with any bony instability the bone must be stabilized preferably with an Ilizarov-type external frame.
    If possible close the skin loosely over drains and ensure that no excessive skin tension is present. If closure is impossible pack the wound open loosely or apply an antibiotic bead pouch and plan for delayed closure or skin grafting at a later time (Fig. 16-14C).
    Appropriate antibiotics should be used before during and after the operation.
AFTERTREATMENT
The limb is splinted until the wound has healed, and then it is protected to prevent pathological fracture. Antibiotic treatment is continued for a prolonged period and should be monitored by an infectious disease consultant.
Bony and soft-tissue defects must be filled to reduce the chance of continued infection and loss of function. The methods described to eliminate this dead space are (1) bone grafting with primary or secondary closure; (2) use of antibiotic polymethyl methacrylate (PMMA) beads as a temporary filler of the dead space before reconstruction; (3) local muscle flaps and skin grafting with or without bone grafting; (4) microvascular transfer of muscle, myocutaneous, osseous, and osteocutaneous flaps; and (5) the use of bone transport (Ilizarov technique).
Open Bone Grafting

Papineau et al. described an open bone grafting technique for the treatment of chronic osteomyelitis. This procedure is based on the following principles: (1) granulation tissue markedly resists infection, (2) autogenous cancellous bone grafts are rapidly revascularized and are resistant to 
infection, (3) the infected area is completely excised, (4) adequate drainage is provided, (5) adequate immobilization is provided, and (6) antibiotics are used for prolonged periods.

The operation is divided into three stages: (1) excision of infected tissue without or with stabilization using an external fixator or an intramedullary rod, (2) cancellous autografting, and (3) skin closure.
TECHNIQUE  
Papineau et al. 
STAGE I: DéBRIDEMENT
 •    Use a pneumatic tourniquet if possible.
 •    In this stage, completely excise the sinus tracks and sequestra, and saucerize the areas of devitalized bone. It sometimes may be necessary to resect the diaphysis in segments, such as in cases of infected nonunion.
 •    If the demarcation between healthy and infected tissues is difficult to recognize, repeat this stage at intervals of 5 to 7 days. Between the operations, pack the wound open with dressings soaked in antibiotic, or use an antibiotic pouch technique (described later).
 •    If stabilization is required, an external fixator is applied at this time. Papineau et al. recommended an intramedullary nail for stabilization.
 •    After 4 or 5 days, begin dressing the wound daily; excise infected tissue as necessary, and delay the next stage until signs of infection are absent, and healthy-appearing granulation tissue is present throughout.
STAGE II: GRAFTING
 •    This stage consists of autogenous cancellous bone grafting, preferably from the posterior iliac crest. Papineau et al. recommended taking the graft in strips 3 to 4 cm long.
 •    Place the grafts in concentric and overlapping layers, and fill the cavity completely.
 •    In the area of resection, envelop the previously “fish-scaled” bone ends with the strips to recreate the shape of the diaphysis.
 •    Pack the wound open with dressings soaked in antibiotics.
 •    Change the first dressing between the third and fifth days, and replace any grafts that adhere to the dressing. Change the dressings until the grafts stabilize.
 •    If indicated, use local muscle pedicle grafts to enhance the blood supply to the grafts, and leave the overlying skin and subcutaneous tissue open.
 •    Especially in subcutaneous bones such as the tibia, excise the lips of the wound if the skin tends to cover the granulation tissue before it completely covers the graft.
STAGE III: WOUND COVERAGE
 •    In some cases, spontaneous epithelialization results in adequate wound coverage; otherwise, in stage III use one of several techniques, including skin grafts, myocutaneous flaps, muscle pedicle flaps, and free flaps requiring microvascular anastomosis to obtain adequate coverage.

Polymethylmethacrylate Antibiotic Bead Chains
The use of antibiotic-impregnated PMMA beads in the treatment of chronic osteomyelitis is common practice. This has the advantage of obtaining very high local antibiotic concentrations (200 times higher than systemic antibiotic), while maintaining low serum levels and low systemic toxicity. The antibiotic is leached from the PMMA beads into the postoperative wound hematoma and secretion, which act as a transport medium. High concentrations of the antibiotic can be achieved only with primary wound closure; if such closure cannot be performed, the wound can be covered with a water-impermeable dressing (bead pouch technique). Before the beads are implanted, all infected and necrotic tissue should be adequately débrided surgically, and all foreign material should be removed. Suction drains are not recommended because the concentration level of the antibiotic is diminished when they are used.
Aminoglycosides are the most commonly used; Penicillins, cephalosporins, and clindamycin are eluted well from PMMA beads; vancomycin elutes much less effectively. Fluoroquinolones, tetracycline, and polymyxin B are broken down during the exothermic process of cement hardening and cannot be used with PMMA beads. Porous, high-viscosity cements, by providing greater surface area, may allow antibiotics to elute more readily than less porous cements. Currently, most commercially available bone cements have a prepackaged form available with gentamicin (500 mg per 40 g pack). We generally add 2 to 4 g of vancomycin to each pack because methacillin-resistant S. aureus is the most common bacterium we see in this setting.
TECHNIQUE  
Henry, Ostermann, and Seligson
 •    Thoroughly débride all necrotic tissue as previously described. Irrigate the wound using a pulsatile lavage system with 9 L of saline solution containing bacitracin.
 •    Prepare antibiotic PMMA beads by mixing high-viscosity bone cement powder with a powder form of the antibiotic in a bowl. Add the activating solution, and stir the mixture until the cement is workable.
 •    Form several beads by rolling them into small spheres. Place the beads on an 18-gauge or 20-gauge wire to form a bead chain. Allow the cement to harden. Record the number of beads on the chain to ensure all beads are accounted for on removal.
 •    Place the PMMA antibiotic bead chains into the bony defect filling the dead space. Close all wound extensions with interrupted nylon sutures.
 •    Dry the skin edges surrounding the wound, and apply a benzoin solution to the skin edges circumferentially.
 •    Apply an adhesive porous polyethylene wound film (OpSite) to cover the wound. A second layer with a larger OpSite or Ioban is placed over the first dressing to prevent leakage.
AFTERTREATMENT
The limb should be appropriately immobilized. The bead pouch should be changed at 72-hour intervals with repeat débridement and irrigation until the wound is ready for a soft-tissue coverage procedure.
Antibiotics
90% of the cases of acute hematogenous osteomyelitis children are caused by coagulase-positive staphylococci. For patients who are not allergic to penicillin, a semisynthetic penicillin that is β-lactamase resistant should be chosen. The antibiotic of choice is either oxacillin or nafcillin. Methicillin is also effective, but this antibiotic carries a higher risk of interstitial nephritis than do the others. In choosing nafcillin, be careful with peripheral needle sites for the administration of the drug IV, because nafcillin may cause significant sloughing of the skin and subcutaneous tissues if infiltration of the IV solution occurs. Cefazolin is an acceptable alternative, at a dosage of 150 mg/kg/24 hr, in place of the semisynthetic penicillin. In patients with identifiable risk factors for MRSA, empiric use of vancomycin is considered. Clindamycin has generally been effective in treating community-acquired MRSA infections in children, including acute osteomyelitis, and in patients allergic to penicillin. Patients with life-threatening infections likely to be staphylococcal be treated empirically with both vancomycin and a semisynthetic penicillin such as oxacillin or nafcillin.
The recommended dosage of oxacillin is 150 to 200 mg/kg administered in divided doses over 24 hours. The current mode of therapy involves a shorter period of initial IV therapy, given a good response by the patient, followed by oral therapy.
Combined IV and oral antibiotic therapy has now become accepted as the standard treatment for acute hematogenous osteomyelitis. The current regimen is to begin treatment of the patient with IV antibiotics. If the patient responds quickly to this form of therapy, consider switching the child to oral antibiotics (Table). To do this, the patient must meet certain requirements (Table).
Antistaphylococcal antibiotic therapy is started while awaiting the culture results. It is important to retain the bacteria so that the laboratory may test it against the antibiotic being used to be certain that adequate blood levels can be obtained. If the child responds quickly to the initial therapy with IV antibiotics, consider beginning oral therapy. The IV antibiotics are continued for at least 5 days, oral therapy is begun 5 to 7 days after. Treatment should continue for a total of 4 to 6 weeks, which includes the time of IV and oral therapy combined (Table).
TABLE. Doses of Antibiotics Used in Osteomyelitis
Medication
Daily Dose in mg/kg
(adult maximum)
Interval in Hours
Intravenous
Nafcillin or Oxacillin
150-200
(12 g)
6
Cefazolin
100-150
(6 g)
8
Clindamycin
40
(2.7 g)
6-8
Vancomycin
60
(4 g)
6-8
Foot Puncture Wounds:
Ceftazidime
150
(6 g)
8
Cefepime
150
(4 g)
8
Piperacillin
200-300
(18 g)
4-6
Ticarcillin (+/- Clavulanate)
200-300
(24 g)
6
Tobramycin
5-7.5
(5 mg)
8
Oral
Dicloxacillin
100
(2 g)
6
Cephalexin
150
(4 g)
6
Cefadroxil
50
(2 g)
12
Clindamycin
20
(1.8 g)
6-8
Rifampin (not appropriate for monotherapy)
20
(600 mg)
12
Foot Puncture Wounds:
Ciprofloxacin (see text for comment on use in children)
30
(1.5 g)
12
TABLE. Contraindications to Oral Antibiotic Therapy
·   Inability to swallow or retain the prescribed medicine
·   Questionable or unreliable gastrointestinal absorption of antibiotics (e.g., short bowel syndrome, Crohn's disease, neonates)
·   Inadequate response to intravenous therapy
·   Response to intravenous antibiotic for which there is no oral equivalent (e.g., vancomycin) and etiologic agent not established
·   Infection with organism for which there is no effective and acceptable oral antibiotic (e.g., multidrug resistant staphylococci)
·   Parents' and patient's strict compliance with prescribed oral regimen in doubt

If there is adequate response to the IV therapy, oral dicloxacillin may be started at a dosage of 100 mg/kg/24 hr. As an alternative, cephalexin may be administered at a dosage of 150 mg/kg/24 hr. The oral suspension form of dicloxacillin is not palatable, and parents may find it difficult to persuade young children to swallow it. For that reason, cephalexin may be preferred, as the oral suspension of this antibiotic is more palatable. Cephalexin may also be used as the IV drug, at a dosage of 150 mg/kg/24 hr, in place of the semisynthetic penicillin. The oral dosage of clindamycin is 30 mg/kg/24 hr IV, followed by 50 mg/kg/24 hr by mouth, in patients allergic to penicillin. Clindamycin has excellent oral bioavailability, but as with dicloxacillin, the oral suspension has an unpleasant taste that may contribute to therapeutic noncompliance.
MRSA is more common pathogen in bone and joint infections in children. Any child who does not respond appropriately to adequate therapy should be considered to have infection caused by MRSA.
For methicillin-resistant staphylococcal organisms one should use vancomycin, 50 mg/kg/24 hr IV, combined with rifampin, 15 mg/kg/24 hr orally as covered earlier.
Biodegradable Antibiotic Delivery Systems
Biodegradable antibiotic delivery systems offer a significant advantage over PMMA in that a second procedure is not required to remove the implant. Some of these biodegradable substrates contain osteoconductive and osteoinductive materials, which can be used to promote new bone formation.
Closed Suction Drains
Closed suction antibiotic ingress and egress high-volume irrigation systems can be used over 3 to 21 days; however, because of the risk of secondary contamination and infection with new organisms, most surgeons have abandoned this treatment method.
Soft-Tissue Transfer
To fill dead space left behind after extensive debridement may range from a localized muscle flap on a vascular pedicle to microvascular free tissue transfer. The transfer of vascularized muscle tissue improves the local biological environment by bringing in a blood supply that is important in the host's defense mechanisms and for antibiotic delivery and osseous and soft-tissue healing. The success rates are from 66% to 100%.
For tibia, gastrocnemius muscle is used for proximal third defects of the tibia, and the soleus muscle is used for middle third. A microvascular free muscle transfer is required for distal third of the tibia.
Microvascular transfer of tissue may consist of muscle that is covered with a skin graft or a myocutaneous, osseous, or osteocutaneous flap. Adequate initial débridement of the involved area, so that the flap is placed in a healthy environment, helps to ensure the success of the procedure.
When a microvascular free muscle flap is used, and segmental bone loss has occurred, autogenous cancellous bone grafting can be done about 6 weeks after the initial free flap transfer. A free fibular graft can be used for segmental bone loss of the tibia. If chronic osteomyelitis involves segmental bone loss of the tibia and the fibula, the results of a free fibular graft are not good, and amputation or reconstruction by the Ilizarov technique is advised.
Ilizarov Technique
In chronic osteomyelitis and infected nonunions, it allows radical resection of the infected bone. A corticotomy is performed through normal bone proximal and distal to the area of disease. The bone is transported until union is achieved. Disadvantages of this technique include the time required to achieve a solid union and the high incidence of associated complications. An average of 6 months for union is seen.
Hyperbaric Oxygen Therapy
It has not proved to be reliably effective. The use of hyperbaric oxygen can be recommended only as an adjuvant to more traditional methods of treatment.
Neonatal Osteomyelitis
Its a different disease from that seen in children, because of the variety of organisms involved, the frequency of multiple sites of infection, and the presence of transphyseal vessels until age 12 to 18 months, which leads to infection on both sides of the physis. As a result, the infection destroys the center of ossification of the epiphysis and the physis itself, producing complete growth arrest (Figure 5-3). This is most likely to occur in the proximal femur, where the result is destruction of the head of the femur. The infection frequently spreads out of the involved epiphysis into the joint, producing a septic arthritis. It produces fewer clinical and laboratory signs than in the child. Although Staphylococcus may be the etiologic agent of the osteomyelitis, Gram-negative organisms and group B Streptococcus are also common; therefore, antibiotics that cover all of the organisms must be given while awaiting the results of cultures. Neonates with acute hematogenous osteomyelitis frequently have multiple sites of involvement—as often as 40% of the time. Infants with multiple sites of osteomyelitis are usually sick before the onset of the infection, and most have an umbilical catheter. Infants with single sites of osteomyelitis have a milder disease and are generally less ill than those with multiple sites of infection.