acute and chronic adult osteomyelitis and prosthesis-related infections

8

Acute and chronic adult osteomyelitis andprosthesis-related infections

Patricia Muñoz MD, PhD

Associate Professor of Clinical Microbiology

Emilio Bouza MD, PhD

Chief Professor of Clinical Microbiology

Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario ‘Gregorio Marañón’,Universidad Complutense, Madrid, Spain

Both acute and chronic osteomyelitis are causes of rising concern, mainly because of theincreasing number of traumatic accidents, the appearance of new groups of patients at risk,the widespread use of prosthetic devices and the emergence of new patterns of anti-microbial resistance. Classification systems, clinical features and risk factors will bereviewed. Diagnosis is usually clinical and microbiological, but imaging techniques such asplain radiography, radionuclide imaging, computed tomography and magnetic resonanceimaging are commonly used. Decisions regarding the best imaging modality can be challeng-ing and should reflect the location of the suspected infection and any associated illnesses orbone disorders. Osteomyelitis is characteristically recurrent, needs multiple surgical inter-ventions and is resistant to short courses of therapy. The application of more precise diag-nostic techniques and the availability of non-toxic, highly efficacious oral antimicrobial agentsfrequently permit a long-term ambulatory approach. The optimal length of therapy has notbeen established.

Key words: osteomyelitis; chronic osteomyelitis; acute osteomyelitis; infected non-unions;infected joint prosthesis; spine infection; Staphylococcus aureus; scintigraphy; magnetic resonanceimaging; computed tomography; plain X-rays; technetium; gallium; surgery; amputation; surgicaldebridement; external fixation; Ilizarov.

DEFINITION AND CLASSIFICATION

The term ‘osteomyelitis’ is used to describe any infection involving bone and bonemarrow (Hass and McAndrew, 1996). Such infections are usually classified accordingto several characteristics (Table 1) since, to date, there has been no universallyadopted system able to predict aetiology, guide therapeutic strategy or provideprognostic data or uniform criteria for comparative studies (Laughlin et al, 1995). Thedevelopment of a unique staging system (similar to those used in oncology)incorporating the essential elements of all of them is a vitally important task for thefuture (Mader et al, 1996).

Some of the most important factors to take into account are outlined below.

Baillière’s Clinical RheumatologyVol. 13, No. 1, pp 129–147, 1999

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Age of the patient

The pathogenesis and aetiology are usually different in the newborn, children andadults. In this chapter, we will deal only with adult infections.

The bone involved

The long bones of the lower limbs are more susceptible to infection because theirblood supply is poorer. They also bear more weight and have a worse venous return.The pelvic and cranial bones are infrequently involved.

Host nutrition, immune competence and co-morbidity

High-risk groups must be considered here. In intravenous drug abusers, atypicallocations of infection (pubic bones, clavicle or vertebrae) are more frequentlyencountered, and Gram-negative rods, mainly Pseudomonas aeruginosa, and yeasts haveto be considered as potential aetiological agents. Patients with haemoglobinopathies, forexample sickle-cell disease, have a higher incidence of infection caused by encapsulatedbacteria such as Streptococcus pneumoniae, Haemophilus influenzae or Salmonella.Chronic haemodialysis is also a risk factor for osteomyelitis, the most common sites ofinvolvement being the ribs and thoracic spine.

Aetiology

Regardless of the type of osteomyelitis, a specific microbiological diagnosis is essential.It is not possible to predict the microbial aetiology based on epidemiology or clinicalpresentation. In chronic osteomyelitis, organism(s) isolated from sinus tract drainagemay not accurately reflect organisms present in the bone.

Most cases of osteomyelitis are caused by Gram-positive bacteria, but practically anyother micro-organism may be responsible for bone infection. Gram-negative bacteriaare frequently found in post-traumatic and post-surgical osteomyelitis, and anaerobicor mixed infections have also to be considered in osteomyelitis in those with a poorvascular supply, for example diabetics. Mycobacterium spp. (particularly M. tuberculosis)are still an important cause of osteomyelitis and may be associated with other micro-organisms (staphylococci). Finally, fungal infections of bone have been described for allagents responsible for systemic mycosis, in both the normal and the immunocompro-mised host. This aspect is analysed in Chapter 2.

130 P. Muñoz and E. Bouza

Table 1. Different classification criteria for osteomyelitis.

Criteria Classification

Age Children—AdultsBone Affected Long—ShortHost Drug abusers—Immunosuppressed—NormalAetiology Bacterial—Non-bacterialPathogenesis Haematogenous—ContiguousExistence of fracture Consolidated—Non-unionRisk factors With/without prosthetic materialBlood supply Adequate—InadequateEvolution Acute—Chronic

Pathogenesis

Taking into account the mechanism by which the infecting organisms reach the bone,osteomyelitis may occur as a result of haematogenous seeding, secondary to acontiguous focus of infection or by direct traumatic or surgical inoculation.

Underlying fracture

The existence of an underlying fracture or non-union (pseudoarthrosis) is of greatimportance since it will influence the surgical approach. Major risk factors for boneinfection are contaminated open fractures, previous surgery, the insertion ofprosthetic material, delayed post-operative wound-healing and previous infections(Gillespie, 1990). Any traumatized bone may become infected.

Prosthetic material

The presence of prosthetic material near the infection site must be carefully soughtsince it helps to prolong the disease, increases the pathogenicity of micro-organismssuch as Staphylococcus epidermidis and hinders the efficacy of the antimicrobialtreatment. Although the withdrawal of these materials is regularly recommended, it isneither always necessary nor possible.

Vascular supply

The importance of bone vascular supply has been stressed by Waldvogel andcolleagues (Lew and Waldvogel, 1997). The most characteristic example of osteo-myelitis with bad vascular flow is that it is associated with infections of the diabeticfoot. Neuropathic and vascular changes characteristic of diabetes mellitus put sufferersat risk of developing chronic foot wounds, and subsequent bone infection, after minortrauma.

Acute or chronic nature

In terms of disease activity, osteomyelitis can be classified as acute or chronic.Osteomyelitis is considered to be acute when symptoms are of recent origin and noprevious therapy has been provided. On the other hand, osteomyelitis is chronic if thesymptoms have lasted for 4–6 weeks, when a previous therapeutic approach has beentried or when it follows open fractures or surgical procedures. Chronic osteomyelitisimplies the presence of dead bone and the frequent need for surgery to effect a cure.An infection of prosthetic material may be ‘chronic’ from the beginning.

This classification is important since therapy and prognosis will be very different indifferent circumstances. At present, fewer than 6% of cases of haematogenousosteomyelitis become chronic, but all post-traumatic infections should be consideredas chronic.

Cierny and Mader have proposed a praiseworthy classification for adult chronicosteomyelitis that takes into account the anatomical status of the bone lesion, theinvolvement of soft tissues and the expected host response to infection (Mader et al,1996) (Table 2). Nevertheless, the system has not been broadly incorporated intoclinical practice. Each case should be classified with a number and a letter.

Acute and chronic adult osteomyelitis and prosthesis-related infections 131

Anatomical classification

● Type I: endosteal disease or infected (but consolidated) fractures with anintramedullary rod. Surgical treatment is simple and will not promote boneinstability.

● Type II: a coverage defect of cortical bone infection (pressure sore). Bone excisionis easy, although soft tissue coverage may be more complicated.

● Type III: osteomyelitis affecting cortical bone and marrow but not including thewhole bone circumference (sequestrum). Surgical debridement is complicated,although it does not promote instability.

● Type IV: osteomyelitis affecting the complete circumference of the bone. Thesurgical approach usually requires the ablation of a bone segment and promotesbone instability. Type IV: includes infected non-unions and infected articularprostheses.

Physiological classification

● Class A: patients and tissues with normal response to infection and surgery.● Class B: patients with local or systemic deficiencies that are supposed to promote

a delayed healing and response to infection (Table 3).● Class C: patients not considered to be suitable surgical candidates, for whom the

morbidity of treatment is greater than the morbidity of disease or exceeds theexpected gain.


Table 2. Cierny–Mader classification for adultchronic osteomyelitis.

Anatomical Type I MedullaryType II SuperficialType III LocalizedType IV Diffuse

Physiological Class A Normal hostClass B Compromised patientClass C Poor-risk candidate

Table 3. Local and systemic factors that affect theimmunological, metabolic and vascular response toosteomyelitis.

Systemic Local

Malnutrition Chronic lymphedemaRenal or hepatic failure Venous stasisImmunodeficiency Great or small vessel diseaseNeoplasm ArteritisDiabetes mellitus ScarsExtremes of age Post-radiation fibrosisSmoking Loss of local sensationChronic hypoxiaParenteral drug abuse

Some negative aspects of this classification are that it considers neither the aetiologynor the bone involved. The strongest predictor of failure is local or systemic immuno-compromise.

ACUTE PYOGENIC OSTEOMYELITIS IN ADULTS

Acute haematogenous osteomyelitis (AHO) is more common in children, although thecondition is now increasingly seen in adulthood rather than childhood, with aninsidious onset instead of an acute one and being caused by Gram-negative rather thanGram-positive organisms (Torda et al, 1995).

In adults, AHO most frequently involves the spine (Bateman and Pevzner, 1995),probably because of its abundant red marrow and slow and tortuous blood flow.Bacteria reach the vertebral bodies preferentially via the arteries but occasionally alsothrough the venous plexus. The plate, disc and vertebral body may be destroyed duringvertebral osteomyelitis (Calderone and Larsen, 1996). The sternoclavicular and sacro-iliac joints, and the symphysis pubis, may also be involved. Infection typically affects firstsubchondral bone and then spreads to the joint space.

Over 50% of episodes of vertebral osteomyelitis are caused by S. aureus,approximately 30% by Enterobacteriaceae and the remaining 10–20% by other micro-organisms, for example Brucella spp., M. tuberculosis and fungi (Jensen et al, 1998).Other micro-organisms, such as S. epidermidis, have also been identified in thissetting.

Pain that increases with vertebral column movement is the most common clinicalmanifestation of vertebral osteomyelitis. Other symptoms depend on the location ofthe infection (hip or abdominal pain, stiffness, muscle spasm or meningeal signs).Patients with cervical osteomyelitis and pre-vertebral abscesses may present withodinophagia or dysphagia.

Presentation is usually subacute (Ozuna and Delamarter, 1996). Fever and/or anelevated white blood cell count may be absent in up to half of the cases. An increasederythrocyte sedimentation rate (ESR) may be a useful tool for the diagnosis of activevertebral infection.

Overall, the lumbar spine is involved in more than 50% of episodes of vertebralosteomyelitis, 35% being located in the dorsal spine and the remaining 15% in thecervical spine. Lumbar osteomyelitis occasionally occurs as a septic metastasis ofinfections of the pelvis and genitourinary tract.

AHO constitutes a diagnostic challenge since its clinical and radiological mani-festations may be non-specific, and its rapid evolution may result in significant neuro-logical sequelae. Most cases of vertebral osteomyelitis have plain X-ray abnormalitieswhen first seen, but in cases with a very acute presentation, pain may occur withnormal plain films. Erosive, irregular images in the vertebral bodies and their adjacentintervertebral discs are common. Pre- and paravertebral abscesses and vertebralcollapse are common complications.

Isotope imaging is highly sensitive in patients with negative or imprecise plainX-rays. Both computed tomography (CT) and magnetic resonance imaging (MRI)offer early and precise images that are very useful for surgical or aspirativeorientation.

Aetiological confirmation requires positive blood cultures, vertebral material orboth. Only a quarter of the episodes are documented by blood culture; consequently,bone aspiration should be undertaken whenever possible.


Most cases of vertebral osteomyelitis do not require surgical debridement. Surgeryshould be reserved for patients with spinal instability, those with neurologicalimpairment, patients with a large progressive abscess impossible to drain by guidedneedle aspiration and those with an unknown aetiology not responding rapidly toantimicrobial therapy (Arnold et al, 1997).

Empirical therapy must be initiated after the collection of blood and infected bonefor culture. Immobilization in bed is only required for patients with pain or vertebralinstability, and, in most cases, casts are not necessary.

LOCAL RESPONSE OF BONE TO INFECTIONS: INFLUENCE ON TREATMENT

The clinical course of osteomyelitis is characterized by a tendency toward chronic,recurrent infection. Although most recurrences develop in the first year, long-termdelays have been described, proving that the micro-organisms are able to survive in thebone. This may be partly explained by the capacity of the micro-organisms to adhereto either natural solid surfaces or prosthetic materials, and to synthesize glycocalyx.Biofilm production protects the bacteria from antibodies, phagocytosis and themajority of cell wall active antimicrobial agents. Tissue perfusion and intramedullaryoxygen tension are reduced in infected fractures. Finally, surgical implant material hastoxic effects on host defences.

A brief review of the pathogenesis of osteomyelitis is necessary to help tounderstand the moment at which each imaging technique becomes appropriate. Oncethe micro-organism reaches the bone, a suppurative reaction is produced, followed bymarrow oedema, which can be readily detected only by MRI. The next step consists ofvascular congestion, thrombosis and ischaemia. At that moment, soft tissue changesmay already be detectable on CT but not with plain X-ray technology. Finally (after atleast 2–3 weeks), bone reaction begins, with the production of new periosteal bone,sequestrum, decalcification and neosteogenesis that can be detected even using plainfilms.

The local pathological anatomy also depends on the route of infection. Initially,haematogenous infection is medullary, extending to involve the cortex, sub-periosteal space and soft tissues. Post-traumatic osteomyelitis initially involves thecortex.

CHRONIC PYOGENIC OSTEOMYELITIS IN ADULTS: CLINICAL FEATURES

Chronic osteomyelitis is usually a local disease that only rarely produces systemicmanifestations. Fever is more common in acute infections or in the presence of softtissue abscesses.

Failure of the patient to follow a normal recovery process or the presence of localor systemic signs of infection should arouse the suspicion of osteomyelitis. The mostcharacteristic symptom is constant pain. The onset is usually gradual, and the painincreases with movement. Rigidity, as a result of ‘protective’ muscular contraction, isalso a common finding.

The detection of a sinus tract with suppurative drainage will establish the diagnosisin an adequate clinical setting and mark the clinical activity of osteomyelitis. Distal


oedema, caused by the physiological decrease of venous and lymphatic return inresponse to infection, may also be encountered.

Most patients with chronic osteomyelitis present with a past history of acuteinfection and a relapse (or several relapses) of pain, erythema, swelling, fluctuation anddischarge from a sinus. Between relapses, the patient may be asymptomatic or have apersistent sinus discharge.

DIAGNOSTIC APPROACH: ACTIVE OSTEOMYELITIS OR SEQUELAE?

The diagnosis of osteomyelitis and prosthetic joint infections is usually made on thebasis of clinical, laboratory and imaging techniques. The gold standard is histologicaland microbiological examination of the bone. Although the problem is usuallylocalized, a detailed history should be taken and a complete examination performed(Levine et al, 1993). Data regarding the presence of any kind of prosthetic material,previous surgical and medical therapy, the length of any antimicrobial courses andthe response obtained, and the volume and odour of the discharge must becarefully recorded. In most cases, the diagnosis is almost established after taking thehistory, and imaging and laboratory aids are used to confirm the site, size andactivity of the infection, and to determine the aetiological agent. Experiencedclinicians place much more reliance on clinical data than on imaging or laboratorytests.

Physical examination should address evaluation of the integrity of the involvedosteomuscular tissues, inflammatory signs, pain, bone instability, sinus tracts andneurovascular changes. The nutritional status of the patient should also be considered.

Laboratory investigations

Analytical data are not essential for the diagnosis of osteo-articular infections. The ESRis usually high with active infections (92%) and tends to decrease after efficacioustherapy. However, there is no direct relationship between the ESR and the severity ofinfection, nor should it be used as a guide to the duration of treatment. Its accuracyin infected prostheses is variable. In our experience, the ESR is not useful as an indexof activity or cure in osteomyelitis.

The level of C-reactive protein is usually also increased, although this measure is lesswell studied and lacks specificity. Levels increase after surgery, but a raised level 2months or more after joint replacement may be a marker of infection.

Only 35% of patients have leukocytosis at the time of admission.In summary, no single laboratory parameter is reliable enough to be of routine value

in the diagnosis of osteomyelitis.

Imaging techniques

Although the site of pain and tenderness provides a useful clue to the site of infection,imaging plays an important role in establishing the diagnosis and directing the treat-ment of osteomyelitis. However, confirmation that the changes seen on the images arethe result of infection can only be obtained by identification of the organisms present(Bohndorf, 1996).


Plain X-rays

For an acute osteomyelitis to be detectable in a plain X-ray, a 35% loss of the calciumcomponent is required in the bone lesion. This usually takes a minimum of 15 days. Atthis stage, examination of the soft tissues may reflect the presence of swelling causedby pus or oedema. This is not a problem in chronic osteomyelitis, in which the dilemmausually involves establishing whether radiological changes correspond to activeinfection, surgical sequelae or just trauma (Elgazzar et al, 1995).

The changes that occur in the bone are those of destruction and repair (theresponse of the periosteum and bone marrow to insult being to form bone). Thedetection of a sequestrum (a clearly defined dense isolated area surrounded by anosteopenic zone, which is in turn demarcated by a radiodense zone) or an involucrum(newly formed living bone appearing as a hyperdense zone under an elevatedperiosteum) is considered pathognomonic of osteomyelitis. Other signs suggesting thepresence of active infection are the detection of poorly delineated osteolytic areas, aloss of cortical continuity, periosteal hyperplasia and irregular periosteal bone extend-ing into the adjacent soft tissue.

Signs of activity in chronic osteomyelitis include a change from the previous X-rayin both bone and soft tissues, ill-defined osteolysis, periostitis and sequestration(Norden et al, 1994).

The presence of peri-prosthetic bone reabsorption or new periosteal boneformation is, in the appropriate clinical circumstances, highly suggestive of infection.Considering their simplicity and low price, conventional X-rays should always beobtained if osteo-articular infection is suspected.

Tomography

Sequential tomographic cuts may provide a clearer location of any opacities. Theirmajor role is in the detection of sequestra in chronic osteomyelitis.

Sinography

When a chronic discharging sinus is present, the injection of a contrast agent into thecutaneous opening may provide an excellent picture of its extent, path and volume.This has proved to be a useful guide for surgical treatment.

Isotope bone scanning

In most cases of chronic osteomyelitis, clinical and radiological data permit an easydiagnosis. However, bone changes as a result of other conditions, and soft tissueinfection, sometimes render laboratory and X-ray signs unreliable as indicators ofosteomyelitis. This regularly happens in acute haematogenous osteomyelitis. In thissituation, scintigraphic methods may be helpful. Scintigraphy is, because it providesmetabolic data, also useful in evaluation of the therapeutic response. However,anatomical definition is clearly inferior to that obtained using CT or MRI. We willbriefly comment on the widely used techniques, although more sophisticated methodsof investigation are being developed (Becker et al, 1996).

99mTc methylene diphosphonate. 99mTechnetium methylene diphosphonate (MDP) is takenup by areas of increased blood flow or osteoblastic activity. Three-phase MDP bone


scanning (vascular, pool and late or bone phase) increases specificity and is the first-line diagnostic imaging technique after a plain X-ray in the evaluation of suspectedosteomyelities (Caglar et al, 1995).

The image quality is rather good, the dose of irradiation small, and the costreasonable, and the technique is available in most centres. Preparation is simple, andit provides an earlier and more sensitive diagnosis than do plain X-rays.

Specificity is, however, poor, the most reliable parameter of this technique being thenegative predictive value, although false negatives have also been described. Falsepositives may be related to neoplasm, fractures, heterotopic ossification, arthritis,neuropathic osteopathy, trauma and arthrosis. It is not very useful in children or inbone that has recently undergone surgery.

67Gallium citrate. This compound is taken up by areas where leukocytes or bacteriaaccumulate, providing quantitative information about inflammatory activity. Thecomparison of a gallium scan with the MDP scan is useful.

Gallium scans become positive earlier than MDP scans and are sensitive in thedetection of active bone and joint lesions. A normal gallium scan virtually excludes thepresence of an inflammatory process.

False-positive gallium scans in non-union or after recent surgery are common. Adultpatients with previous bone disorders and possible osteomyelitis, or patients withdubious MDP scan results, should have a gallium scan. Gallium may also be thepreferred technique for follow-up after treatment.

111Indium or 99Tc autologous leukocyte scintigraphy. If the previous bone scans areinconclusive, 111In-leukocyte scintigraphy is the next-line diagnostic imaging technique,particularly in adults with other bone disorders (Nijhof et al, 1997).

The patient’s leukocytes are obtained and labelled. Afterwards, they are infused intothe patient, accumulating in the focus of infection, where they can be detected.

Indium scans have a higher specificity than techniques previously mentioned for thediagnosis of infection, mainly in traumatized bone. They provide very good results indiabetic foot osteomyelitis, delayed union- or non-union-related infection andprosthetic infections.

Indium scans have a higher sensitivity in acute osteomyelitis than in chronic cases(60% versus 100%), probably because of the massive presence of leukocytes in theformer. False positives may appear after trauma, tumours and other osseousdisorders. The quality of the image is inferior to that of technetium scintigraphy,and the technique is not very accurate for the central skeleton. Preparation is longand complex, the major concerns being the hazards associated with withdrawal andhandling of the blood, plus the need to delay imaging for 18–24 hours, thusprecluding a rapid result. Potential replacement agents for 111In-leukocytes includelabelled immunoglobulins and labelled antigranulocyte antibody agents (Becker et al,1996).

Indium scans should be reserved for patients with a suspicion of osteomyelitis in thebones of the lower extremities not diagnosed using other techniques. Neither type ofscan permits differentiation between septic and non-septic inflammatory processeswith sufficient accuracy.

Ultrasonography

Sonographic criteria for the diagnosis of osteomyelitis are:


1. an abnormal collection of fluid adjacent to the bone without intervening softtissues, and elevation of the periosteum by 2 mm;

2. thickening of the periosteum, with hypoechoic zones;3. swelling of the overlying muscle or subcutaneous tissue, which is maximal nearest

the bone. In the hip, joint effusion and thickening of the synovium may also beassessed.

Ultrasound is very useful for detecting soft tissue abscesses and pyomyositis, whichcan be confirmed by needle aspiration guided by ultrasound scanning during theprocedure. It should always be performed when inflammatory signs appear soon afterprosthetic joint surgery.

Computed tomography

This technique accurately detects the increase in medullary density typical of the earlystages of osteomyelitis as well as any subsequent changes in the soft tissues andcortical bone.

Its principal advantage is an excellent definition of cortical bone, including zones ofnecrosis, sclerosis and demineralization, periosteal alterations and adjacent soft tissueswelling.

CT does not provide data on the activity of the infection, and there may be imageinterference caused by the presence of prosthetic material. The main drawback is thehigh radiation dose, which prevents its repeated use.

CT is especially recommended in chronic osteomyelitis prior to surgery. It may helpto delineate any abscesses, sinus tract or sequestrum present. It may also be useful forthe evaluation of an infected joint prosthesis and osteomyelitis of the spine, pelvis andsternum.

Magnetic resonance imaging

MRI easily detects the bone marrow oedema characteristic of the earlier phases ofbone infection. Typical MRI findings include a low-intensity area (an abnormal focaldark signal) within the marrow in T1 and a hyperintense area in T2 (an abnormalbrighter-than-fat signal) sequences. The most specific image of osteomyelitis in MRIis that of an increased signal in medullary bone, with a well-defined lucent margin.Infection must be present for several weeks to allow this reactive margin todevelop.

Bone reaction to fracture or surgery appears as low marrow intensity in T1 and anormal signal in T2 sequences. Sinus tracts and cellulitis appear as hyperintense areasin T2 scanning. In chronic osteomyelitis, MRI demonstrates a well-defined rim of lowsignal intensity surrounding the area of focal active disease (the rim sign).

MRI imaging has proved to be as sensitive as bone scintigraphy in the early detectionof osteomyelitis, and, because of its higher spatial resolution, MRI is often morespecific than planar scintigraphy in differentiating bone from soft tissue infection and inseparating arthritis, cellulitis and soft tissue abscesses from osteomyelitis (Hass andMcAndrew, 1996). MRI may facilitate the differentiation of acute from chronicosteomyelitis and may help to detect foci of active infection in the presence of chronicinflammation or post-traumatic lesions. The patient is not irradiated, and newtechniques, such as fat-suppressed contrast-enhanced MRI, are significantly moresensitive and specific (Hovi et al, 1995).


MRI, however, also has some drawbacks. It images not crystalline hydroxyapatite butthe soft tissues and fluid around and within the bone, so it does not provide veryprecise images of cortical bone. Its utility decreases in the presence of metallicmaterials. False-positive results may be obtained in the presence of neoplasia orintra/extramedullary inflammation. The comparative cost is still high, although it isfalling.

Major indications for MRI are in cases of vertebral and foot osteomyelitis, and whena diagnosis has not yet been established after using the techniques described above.New techniques, for example positron emission tomography, are being been evaluatedin this setting (Guhlmann et al, 1998).

OBTAINING AND HANDLING SAMPLES

This aspect has been covered in more depth in Chapter 2, but we will also mentionsome aspects of this important issue here.

The identification of the causative organism should always be the first step inmanagement (White et al, 1995). With the exception of acute haematogenousosteomyelitis, the aetiological diagnosis usually relies on local samples. The usefulnessof these samples will be strongly influenced by the manner in which specimens areobtained, by the accuracy of their handling and microbiological processing, and by theinformation given to the microbiologist.

The best sample is the one that is more likely to reflect the real causative organism(bone or pus aspiration is better than sinus tract culture). Unopened abscesses areexcellent sources of significant micro-organims. A large enough quantity of materialshould be sent rapidly to the laboratory, and contamination should be carefullyavoided. Timing is also important, and, whenever possible, cultures should be obtainedbefore initiating antimicrobial therapy.

BONE INFECTIONS RELATED TO PROSTHETIC MATERIALS:HOW DOES THE PRESENCE OF PROSTHETIC MATERIALCHANGE THE APPROACH TO OSTEOMYELITIS?

Infection rates following total joint replacement are less than 1% in most centres, butthese infections are becoming increasingly common. Infected prosthetic joints areextremely difficult to treat and often require the surgical withdrawal of foreign bodies,which may be very aggressive when artificial joints are well fixed. Attempts to place anew prosthesis are usually carried out after prolonged courses of antimicrobialtherapy, thus leaving the patient with a major incapacity for a long time.

At least 70% of prosthetic joint infections are monomicrobial, the remaining20–30% being either polymicrobial or undocumented. Among the micro-organismsresponsible, S. epidermidis and S. aureus are far more common than other bacteria,followed by Gram-negative rods and anaerobes.

Chronic infection of an articular prosthesis usually begins with continuous pain,prosthetic dysfunction and even complete loosening. Evident sinus tract drainage maybe absent.

Infections have been classified according to their chronicity into those presenting inthe first 3 months after surgery (type I), those presenting between 3 months and 2years post-operatively (type II) and those occurring more than 2 years post-surgery


(type III) (Coventry, 1975). Type I infections are almost exclusively acquired duringsurgery and may be divided into superficial (involving soft tissues but not theprosthesis) and deep (involving the prosthesis) categories. In group II, most infectionsare surgically acquired, and practically all of them involve the prosthesis. Finally, groupIII infections are acquired by haematogenous spread, and the prosthesis is also usuallyinvolved.

Type I infections with superficial involvement and no evidence of prosthetic dys-function should be treated with antimicrobial agents, the removal of bloodcollections, very prompt soft tissue debridement and irrigation. A high proportionof these cases (approximately 70%) will not require future prosthetic replacement.Even in cases with a deep infection, antimicrobial therapy together with earlydebridement and irrigation save at least 50% of prostheses (Drancourt et al, 1993).If discharge persists following initial debridement and antimicrobial therapy, repeatdebridement is indicated. In many of these cases, exchange of the prosthesis willthen be necessary.

In patients with types II and III infection, the final aim is to preserve a functionalprosthesis with no pain. In patients without prosthetic dysfunction and with no orminimal pain, antimicrobial therapy without surgical replacement of the prosthesisshould be attempted.

Whenever possible, oral antimicrobial agents are preferred, frequently includingrifampicin in a combination regimen (Norden et al, 1986). We maintain the treatmentfor a 6–12-month period provided that an adequate response is rapidly obtained. Incases that relapse, treatment is individualized taking account of variables such as the ageof the patient, functional status and the risk of surgical replacement.

Recently, Drancourt et al have reported an acceptable rate of success (74%) whentreating osteo-articular prostheses infected with staphylococci with prolonged periods(9–12 months) of ofloxacin and changing the prosthesis, when necessary, at the sametime as withdrawal of the infected one (Drancourt et al, 1993).

In patients with pain, prosthetic dysfunction or loosening, surgical replacementbecomes necessary. It may be performed in one or two stages, with a low rate of re-infection. If exchange arthroplasty fails or is contra-indicated, the preferred surgicaloption is arthrodesis.

Regarding an infected osteosynthesis, the main principle is retention of the fracturefixation. Whether debridement and implant exchange are necessary, and when theyshould be performed, must be decided on an individual basis. Here again, wheninfection becomes apparent, evaluation of the wound using ultrasonography may allowthe identification of accumulations of pus or blood requiring drainage or aspiration,and may help to identify the causative organism.

TREATMENT

The treatment of osteomyelitis is not yet completely satisfactory. No experiencedphysician would guarantee a cure to a patient with chronic osteomyelitis, so the firstobjective of the evaluation should be to decide whether simple or radical treatmentshould be instituted (Hass and McAndrew, 1996).

The principles of management should include (Norden et al, 1994):

1. complete microbiological diagnosis;2. assessment of the host defence status;


3. definition of the extent of local disease;4. correct antimicrobial therapy;5. surgical debridement of necrotic and poorly vascularized tissue;6. obliteration of dead space;7. restoration of functional skeletal stability;8. rehabilitation.

Therapy for osteomyelitis requires a multidisciplinary approach, and antibiotics andsurgery must be considered in all cases of musculoskeletal infection. The patient mustbe informed that the potential for reactivation exists for the rest of his life, andattention should be paid to the possibility of work loss, frequent hospitalization andprolonged wound discharge (Bamberger, 1993). Because of the chronic nature of theinfection and its various presentations and surgical approaches, management must beindividualized, taking into account the patient’s quality of life and the expectationsoffered by therapy (Mader et al, 1996). The cure should not be worse than thedisease.

Antimicrobial agents: parenteral versus oral—which and for how long?

When the diagnosis of osteomyelitis has been established, the first question is, shouldI use empirical therapy? Antimicrobial agents should only be administered empirically(after obtaining a blood culture and local samples) in acute osteomyelitis. Once chronicosteomyelitis is well established, the administration of antimicrobial agents is almostnever an emergency, so all efforts should be made to determine the aetiological agent.In this sense, it is advisable not to start therapy until adequate samples have beenobtained.

The next issue is which antibiotic should be used for specific treatment (Mader etal, 1992). The individual antimicrobial drugs and the overall characteristics of theagents used in osteo-articular infection have been reviewed in Chapter 2, so we willcover only some concrete aspects of the antimicrobial therapy, that is the route andthe duration of treatment.

Parenteral agents used to be the drugs of choice for the treatment ofosteomyelitis. Some authors still believe that at least the initial treatment ofosteomyelitis should be carried out using intravenous antibiotics. Others, includingourselves consider that, in clinically stable patients with aetiologically well-documented osteomyelitis, some oral drugs are adequate from the very beginning(Gentry 1990, 1991). For maintenance therapy, intravenous antibiotics have beenlargely substituted by new orally active, wide-spectrum agents, which permitprolonged ambulatory treatment.

Rifampicin and clindamycin are the only agents that appear to have degradativeeffects on biofilm. No other single antimicrobial sterilizes bone (Norden et al, 1994).The most frequently used drugs for staphylococcal infections are combinations ofrifampicin with either oral fluoroquinolones or co-trimoxazole (Gentry, 1993;Galanakis et al, 1997; Rissing, 1997; Sánchez et al, 1997). Most Gram-negativeinfections in adults can be treated with an oral quinolone. When intravenous therapyis needed, out-patient therapy is highly desirable (Graninger et al, 1997).

In summary, we believe that, for chronic osteomyelitis caused by susceptibleorganisms, oral therapy with agents that achieve adequate levels at the site of infectionmay be as effective as parenteral therapy. In addition, probably because of the lowbacterial load, the development of resistance is infrequently encountered.


Length of therapy

New orally active and low-toxicity antimicrobial agents, such as quinolones, have ledto significant changes in the recommended length of therapy for chronicosteomyelitis (Rissing, 1997). The 6-week benchmark, which was determined largelyby experience with childhood haematogenous osteomyelitis, may not be enough forcontiguous focus osteomyelitis after trauma in adults (Dirschl and Almekinders,1993).

Unfortunately, to our knowledge, no well-designed prospective clinical trials haveestablished the precise effective duration of antimicrobial therapy for chronicosteomyelitis. We recommend a minimum of 3 months once all the infected tissue andprosthetic material has been excised. This may be extended in several circumstances,for example a poor initial response, unsatisfactory coverage of the soft tissues, thepresence of non-union and the delayed withdrawal of prosthetic material. However,the superiority of this approach has not been validated.

Occasionally, patients not considered candidates for surgery, require permanentsuppression rather than a curative approach or therapy when relapses are detected.

Local delivery of antimicrobial agents

Several devices designed to deliver antimicrobial agents locally (regional perfusion,external closed suction irrigation, pump irrigation, antibiotic-impregnated implants andcement, and biodegradable microcapsules) have been developed. The most extensivelystudied are gentamicin-impregnated polymethylmetacrylate (PMMA) beads, which areclaimed to provide an immediate filling of the bone loss and to deliver high antibioticconcentrations. Good results in the treatment of infected non-unions and contami-nated compound fractures have been reported. In some centres, this treatment hasbecome standard orthopaedic practice (Cho et al, 1997). The bead chains are left inthe infected bone cavity after debridement, their distal end projecting from the scar.During the following 4–6 weeks, the chain is progressively pulled out. The procedureis painful, and adherence sometimes prevents total extraction of the beads. Althoughit may be a useful option, success rates are difficult to evaluate since most patientsreceive combined surgical and medical treatment (local and systemic antimicrobialdrugs).

The main drawback is the potential danger of leaving a foreign material in a septicspace, connected with the exterior. In addition gentamicin does not seem to be themost adequate agent, considering that S. aureus is the major pathogen. New devicesimpregnated with more active antimicrobial agents, such as vancomycin, teicoplaninand ciprofloxacin, and the use of biodegradable implants, are being studied.

When is surgery needed?

Despite the advances achieved with medical therapy, the successful treatment of post-traumatic chronic osteomyelitis has traditionally been associated with strict adherenceto several basic principles: the complete debridement of necrotic and infected tissue,obtaining bone stability, the elimination of dead space and the provision of a durablesoft tissue coverage (Monsivais, 1996).

Antibiotic treatment does not substitute surgical debridement of the infecteddevitalized bone, and the absence or inadequacy of surgical treatment is clearlyassociated with higher rates of initial failure and recurrence.


On the other hand, experience has taught us that, when dealing with osteomyelitis,surgery is ‘the art of the possible’ and not always a sine qua non. Major functional lossand bone stability must be carefully considered with the surgical team. Besides, the aimof surgical treatment should be cure. If cure is not possible, there are only limited indi-cations for bone surgery (Norden et al, 1994). A conservative non-surgical approachor partial excision may be preferable for asymptomatic or oligosymptomaticosteomyelitis in elderly patients.

In this chapter, we do not intend to review the different surgical techniques for bonedebridement. The main principle is that, when physically possible, only viable boneshould be left in place. The assessment of bone viability is of fundamental importancein this field. The use of vital dyes or laser Doppler flowmetry as a surgical adjunctallowing the quantitative determination of bone vascularity has recently proved to bequite helpful.

When indicated, surgery should ideally be performed before the administration ofantimicrobial agents. The purpose of the surgical intervention may then not only betherapeutic but also serve to establish a precise aetiological diagnosis.

As previously mentioned, acute haematogenous osteomyelitis usually responds toantimicrobial therapy. The presence of an abscess, a metaphyseal cavity caused byhaematogenous osteomyelitis or evidence of spinal cord compression in vertebralosteomyelitis requires surgical treatment. Another situation that requires rapidfunctional reconstruction is sternal bone osteomyelitis associated with mediastinitis(Christenson et al, 1996). For this, wide debridement should lead on to (at the sametime or soon after) chest wall reconstruction by means of pectoral vascularized muscleflaps.

Chronic osteomyelitis implies that dead bone is present, thus requiring surgicaldebridement. On some occasions, lack of bone consolidation and stability precludeearly surgical therapy, so surgery has to be postponed until consolidation is achieved.In such cases, antimicrobial administration is ‘palliative’ and leaves a potentiallycurative and definitive treatment for patients with well-developed bone unions inwhich osteosynthesis material and partial bone debridement are tolerable to thepatient.

When the axial long bones are implicated, aggressive debridement is not easy toperform since wound coverage and mechanical stability may be difficult to achieve ormaintain. The treatment of infected non-unions is especially difficult (Toh and Jupiter,1995). Prognosis has become more optimistic with the description of new orthopaedicmethods such as Ilizarov limb reconstruction, which is cost-effective compared withamputation and which permits compression of the fracture (Dendrinos et al, 1995).Osteotomies, bone grafts, muscular flaps, and even local electrical stimulation, areoccasionally also necessary (Brighton et al, 1995).

Finally, it is important to bear in mind that amputation is sometimes the mostfunctional therapeutic alternative in patients with refractory osteomyelitis of the feetor lower limbs. We feel that early amputation in chronic and relapsing osteomyelitis ofthe feet, particularly when associated with poor vascular supply or neuropathicdisease, is better for the patient than a long course of disability and antimicrobialtherapy condemned to failure.

Administration of hyperbaric oxygen

Open, non-randomized studies suggest the potential usefulness of hyperbaric oxygenin the treatment of refractory chronic osteomyelitis (Mader et al, 1990). Its principal


effect is the enhancement of host defences and repair. Hyperbaric oxygen increasesthe bactericidal activity of phagocytic cells and the bactericidal effect of drugs such asvancomycin and aminoglycosides. Collagen production by fibroblasts occurs moreefficiently with oxygen tensions greater than 10 mmHg.

The definitive role of hyperbaric oxygen in the treatment of human osteomyelitisrequires well-designed prospective clinical studies. Arteritis and radiation fibrosisjustify considering hyperbaric oxygen therapy.

PROGNOSIS AND MONITORING OF TREATMENT

Osteomyelitis-associated mortality is usually low, but the tendency of the condition torecur and become chronic is well known. Patients have to get used to the un-predictable appearance of episodes of fistulous discharge. Recurrences are mostcommon within 1 year of the initial episode, but extremely long delays have beenreported, and suppression may be a better concept than cure.

Antibiotic therapy alone may temporarily suppress chronic osteomyelitis in 70–80%of patients. The combination of antibiotic therapy with correct surgical managementcan achieve arrest of the disease after 2 years in 85–95% of patients with haemato-genous and post-operative infection, and in 80–95% of patients with infected non-unions (Norden et al, 1994).

In any case, the evaluation of patients with chronic osteomyelitis must becontinued for a prolonged period (lifelong if possible), and patients must be toldwhen and why to report without delay. Serial determinations of ESR and plain X-raysmay be useful, but resolution of the signs and symptoms is the best indication ofresponse.

Malignant degeneration arising from a fistula in patients with chronic osteomyelitisis extremely rare, although isolated cases have been described.

PROPHYLAXIS

Antimicrobial prophylaxis is recommended after open fractures, in which the infectionrate is high (Kindsfater and Jonassen, 1995). As previously mentioned, most cases ofchronic pyogenic osteomyelitis in adults are post-traumatic or related to pressuresores or diabetic ulcers. The risk of infection after an open fracture varies widely withthe site, size and nature of the open fracture. Table 4 (Gustilo et al, 1990) rates therisk from zero to 50% in different situations. Infection remains a complicationassociated with considerable morbidity (delayed and non-union, and poor functionaloutcome). According to these data, patients with complicated open fractures shouldbe started promptly on antimicrobial therapy and undergo wound debridement. Someauthors suggest that the adjuvant use of local antibiotic-laden PMMA beads mayreduce the incidence of infection in severe compound fractures (Ostermann et al,1995).

When an articular joint prosthesis is to be implanted, prophylaxis is recom-mended—usually 1–3 doses of cefazolin beginning on the induction of anaesthesia andlasting for a maximum of 24–48 hours.

Although the infection rate is higher following open fracture, the majority of casesof osteosynthesis are carried out on closed fractures (with an infection rate of lessthan 1%). In these cases, peri-operative antibiotic prophylaxis (introduced immediately


prior to surgery and lasting for 12–18 hours) is widely accepted. Antibiotic prophy-laxis is indicated in lower extremity amputation.

As most osteo-articular infections have been shown to be acquired in the operatingtheatre, highly sophisticated centrifugal laminar flow systems have been installed insome suites, achieving a 104-fold reduction of the concentration of micro-organisms inthe environment and a 10-fold reduction in the incidence of infection. At present, the


Table 4. Risk of infection in open fractures (adapted from Gustilo et al, 1990).

Type Wound Fracture Infection

Type I <1 cm Simple, transverse 0–2%Clean puncture Comminution +Soft tissue damage +

Type II >1 cm Moderate contamination 2–7%Moderate contamination Comminution ++Soft tissue damage ++

Type III Soft tissue damage +++ InstabilityComminution +++

III A Soft tissue coverage adequate Contamination ++ 7%III B Loss of soft tissue Contamination +++ 10–50%

Exposure of bone or periosteal strippingIII C Arterial injury 25–50%

Practice points

● Osteomyelitis should be suspected in the presence of a draining sinus tract, anon-union, an open fracture, pain in a patient with a prosthetic joint, or adeep pressure sore

● Acute haematogenous osteomyelitis should be excluded if persistent spinepain or fever appears after a bacteraemic episode

● Osteomyelitis is considered chronic if symptoms have lasted 4–6 weeks, whena previous therapy attempt has failed, or when it follows open fractures orsurgical procedures (including prosthetic material). Chronic osteomyelitisimplies the need for surgery

● An accurate microbiological diagnosis is needed in all types of osteomyelitis.Samples should be obtained before starting antimicrobial therapy

● Imaging techniques are usually needed to confirm the clinical diagnosis and toprepare surgery

● Long-lasting antimicrobial therapy (3–6 months) and surgical debridement ofnecrotic tissue is usually required to treat chronic osteomyelitis. Wheneverpossible, oral therapy is preferred

● The final aim of treatment should be to provide the best possible quality oflife to the patient, so it should always be individualized (age, functional status,risk of surgery)

incidence of infection has been reduced by 0.5% for hip prostheses, while knee andshoulder prostheses are associated with a higher incidence of septic complications(1–4% and 4–7% respectively).

Some orthopaedic surgeons recommend prophylactic antimicrobial agents for theprevention of infection in patients with prosthetic joints undergoing some distalinvasive procedures. A prophylactic approach similar to that for endocarditis isrecommended in the presence of bacteriuria or before the implantation of intra-vascular devices, drainage of purulent collections and dental manipulations.


Research agenda

● A unique staging system able to incorporate aetiological data and to implytherapeutic and prognosis information is needed

● Clear validation of imaging techniques, their indications and positive andnegative predictive values should be more clearly established

● The idoneous length of antimicrobial therapy for different situations, thebenefits of combination regimens and of local antimicrobials have to bedetermined in multicentric studies

● The indications and extent of surgical debridement and of prosthesiswithdrawn have to be established

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acute and chronic adult osteomyelitis and prosthesis-related infections

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