ACUTE OSTEOMYELITIS IN CHILDREN

IDENTIFICATION DATA

Name : Letchumi a/p Paranthaman

Age : 1½ years old

Sex : Female

R/N : 14356/00

This patient is a 1½ years old Indian child who was admitted with history of

left thigh pain and swelling for about a week prior to admission. The swelling was

slowly enlarging and very painful. The child refused to walk. There was no history of

trauma; she had a low-grade fever and cough and had been treated by her GP with

paracetamol and antibiotics.

Clinically she was febrile, irritable and slightly dehydrated. The left hip

revealed a diffused swelling, tender and warm. All movements of the left hip and knee

were limited and painful.

Initial blood investigation shown erythrocyte sedimentation rate was

121mm/hr., total white blood cells count was 23000/ mm and hemoglobin level was

10.8 gm%. The blood culture and sensitivity was negative. The plain radiograph

showed extensive lytic lesion over the metaphyseal part of the upper end of the left

femur. There was no obvious soft tissue swelling. There were no other lesions noted

on her left acetabulum. Ultrasound of her left hip showed no evidence of fluid

collection.

A diagnosis of acute osteomyelitis of the left femur was made. Incision and

drainage was done and revealed necrotic tissues with minimal pus collection around

the femur. The tissue was sending for culture and sensitivity .The culture result

showed Staphylococcus aureus.

1

MANAGEMENT

Intravenous fluid resuscitation was started. Intravenous broad spectrum antibiotic

(cefobid) was given. The antibiotic was continued after the culture tissues result were

available because the organism was sensitive to cefobid and her condition improved.

The intravenous antibiotic was continued for another two weeks followed by four

weeks of oral intake.

DISCUSSION

Osteomyelitis is an infectious process of the bone and its marrow and the term

osteomyelitis is normally refers to infections caused by pyogenic microorganisms but

can be used for granulomatous infections such as tuberculosis, syphilis, viral and

fungal infections (Aprin, 1998). The diagnosis and treatment of osteomyelitis

continue to be a problem. Early diagnosis with prompt and adequate treatment is

essential to reduces the risk of permanent damage and recurrence. Although now day

the mortality of osteomyelitis is relatively rare but the morbidity is still common

despite modern antibiotic and surgical treatment.

Osteomyelitis has commonly been classified based on duration of symptoms,

the mechanism of infection and the type of host response to the infection.

Osteomyelitis has been classified as acute, subacute or chronic, exogenous (cause by

trauma, surgery) or hematogenous, and pyogenic or non pyogenic (Warner, 1991).

Acute hematogenous osteomyelitis is the common type of bone infection and

it is the most common in children. Bacteremia is not necessarily the only etiologic

factor although bacteremia is an almost daily event in childhood, and other etiologic

factors such as a localised trauma or debilitation from chronic illness, malnutrition or

inadequacy of the immune system must be present for the infection to develop

(Morrissy, 1989 and Warner, 1991). Sometimes the exact cause for osteomyelitis

cannot be found.

2

PATHOPHYSIOLOGY

Organisms

Staphylococcus aureus is still the organism responsible for about 50% to 80%

of all such infections in children between one month to five years of age (Aprin,

1988). The second most common are both group A and group B streptococci and in

neonates Haemophilus influenza is an occasional cause that is often associated with

meningitis. There are increasing numbers of gram negative organism causing

osteomyelitis especially in drug addicts. Salmonella osteomyelitis has long been

associated with hemoglobinopathies (Warner, 1991). The other rare organisms such as

Candida albicans can be cultured in patients with diabetes, immunosuppressed

patients with long term antibiotic therapy and premature infants (Akbar Bonakdar-

pour, 1983).

Pathology

Osteomyelitis is most common in the long bone, but neonate multiple sites of

infection are relatively common. Metaphysis is a rapid growing area of the long bone

in children and the most frequently site of involvement. The vascular architecture of

the metaphysis where the nutrient capillaries form sharp loops and terminate as end

vessel predispose to infection following bacteremia. In children more than two years

old, the growth plate acts as a barrier that prevents the metaphyseal abscess from

extending directly into the epiphysis, but in children less than two years, some vessels

cross the growth plate and may allow the spread of infection into the epiphysis and

joint.

The infections causes an inflammatory reaction, local ischemic necrosis of the

bone marrow and subsequently abscess formation. As the abscess increased in size,

increases local intramedullary pressure impaired capillary circulation and this causes

more bone to become ischemic. The purulent material passes through the cortex into

the subperiosteal space and form a subperiosteal abscess and later the periosteum may

3

rupture and pus escapes into the adjacent tissues. Damage to the metaphyseal blood

supply, cause by the release of the bacterial toxins and stripping of the periosteum

cause the portions of the bone to become necrotic. The dead bones, which are

separated from the surrounding viable bone by granulation tissue, are call sequestra

and the periosteal responses are to lay down new bone called the involucrum.

Inadequate treatment results in extensive sequestration of the bone and chronic

osteomyelitis.

CLINICAL FEATURES

The clinical diagnosis of osteomyelitis is difficult especially in the early stages

of the disease (Abiri, 1989) due to wide variation of clinical presentation. The

variation in clinical presentation may be due to interaction of the virulence of the

infecting organism, local environment, age of the patient and resistance of the host

(Wedge, 1988). The classical clinical picture is a short history of pain, swelling,

redness, high fever and impaired function of the infected limb. In infant sometime the

only early manifestation may be failure to thrive. The impaired systemic response to

the sepsis may allow the infant to remain apyrexic and normal white cells count

although the ESR is elevated. But usually the infant is septicemic and very ill, and

very difficult to exclude from other common causes of illness such as meningitis or

pneumonia until a large soft tissue abscess is apparent (Apin, 1988). There is frequent

association with minor trauma and the child may be given analgesic and antibiotics

that mask the systemic signs.

INVESTIGATIONS

Haematology

The white blood cell is raised and the differential shifted to the left, which

generally shows a neutrophil leucocytosis, and sometime mild anemia may be present

(Nade, 1993). The erythrocyte sendimentation rate (ESR) may be normal within the

4

first 48 hours but then raises rapidly and may exceed 100mm/hr and remains elevated

for weeks. Its gradual decline is an indication of a successful response to treatment

(Aprin. 1988).

O”Brian, 1982 however found that elevation of temperature, increased ESR

and raised peripheral white cell count are not specific to osteomyelitis and have little

value in arriving to the diagnosis. These findings are more useful in monitoring the

progress of the disease. C-Reactive protein (CRP ) have been found to be more

sensitive than ESR and WBC in monitoring the progress and respond of the disease

towards therapy.(Kallio,1994).CRP are found to increase and decrease more rapidly

as compared to ESR, thus more sensitive in monitoring the therapy and early

detection of complications.

Blood culture and serology

Blood culture is positive in about 50% to 75% of cases. A positive blood

culture can be obtained in 24 hours, but more time is required for determining specific

antibiotic sensitivity.

Bone aspiration can be done to establishing an accurate bacteriological

diagnosis. A negative aspiration should not rule out the diagnosis. Fine needle bone

biopsy (FNBB) has 87% sensitivity and 93% specificity. It accuracy is increased if it

is done under ultrasound guidance. Interpretation of the results of the biopsy should

be done cautiosly and it is not adiagnostic tool. It is however useful in addition to

clinical findings and radiological evidence to arrive into the diagnosis of osteomyelitis

especially in difficult cases (Howard et al , 1994).

Immunological study for detection of antibodies to the teichoic acid cell wall

of Staph. aureus may be helpful for detecting Staphylococcal osteomyelitis. The test is

more sensitive in acute (82%) than in chronic (43%) osteomyelitis. The cell wall of

Staphylococcus aureus has three components, peptidoglycan, teichoic acid and protein

5

A and the teichoic acid is the major component. The detection and quantification of

teichoic acid antibodies is of great value for early diagnosis of patients with acute

osteomyelitis caused by Staphylococcus aureus and for assessing the clinical response

of patients (Tauzon, 1982). In children younger than three years, H.influenzae type b

is the one of the causes of osteomyelitis and urine should be checked for H.influenzae

type b capsule antigen (Faden and Grossi, 1991).

Radiology

X-ray may show soft tissue swelling, but skeletal changes, such as localized

destruction of bone or periosteal reaction, are not seen for at least 10 to 12 days

(Warner, 1991). Alterations in radiographic density cannot be detected until there is a

decrease of 35 to 50% in bone mineral content (Akbar Bonakdar-pour, 1983).

Radiological diagnosis may be made on the basis of three signs which usually evolve

in the following order (Patton, 1988):-

1. Soft tissue swelling with poor definition of local fat plains.

2. Periosteal new bone formation

3. Focal bone radiolucency

Bone scan

Technetium-99m bone scan can confirm the diagnosis as early as 24 hours to

49 hours after onset in 90% to 95% of patients (Warner, 1991). Technetium 99m-

labelled methylene disphosphonate (99m-Tc-MDP) can be used to differentiate

osteomyelitis from overlying soft tissue lesions. The three phase bone scan shows

well defined increase in uptake in the bone on both the blood pool and the delayed

scan.

The blood pool phase (phase 2) shows the relative vascularity of the area,

whereas the delayed image phase (phase 3) obtained 3 to 4 hour after injection reflects

6

increased uptake in the skeleton. By contrast with the well defined bone uptake seen

in osteomyelitis, there is rather diffuse uptake in cellulitis and septic arthritis.

Gallium-67-labelled scans and indium-111-labeled leukocyte scans may also be

useful in conjunction with the technetium-99m. Gallium citrate accumulated locally

with white cells has high sensitivity to infectious inflammatory precess but variable

and unpredictable sensitivity to other inflammatory condition and if used 48 hours

after technetium will show both isotopes accumulated in the same region of bone

highly suggestive of infection. The accuracy is 62%. The problem with indium-

labeled leukocyte was the time length to prepare the white cell from the sample of the

patient blood and this is not appropriate in a sick patient. This technique is more

accurate and easier to interpret than Tc-Ga scanning with a reported sensitivity of

83%, specificity of 86% and accuracy of 83% (April, 1988 and Scoles, 1980).

Confirmatory bone scan should not be necessary if the diagnosis is clinically obvious

and under no circumstances should appropriate treatment be delayed while awaiting

such a test.

Bone scan should be reserved in difficult site of involvement, eg, pelvis ,

shoulder or foot. False positive are due to contagious soft tissue infection with

secondary hyperaemia of the surrounding bone (Charles, 1980). Israel, 1987

differiantiate this finding by comparing the ratio of uptake at 24 hours to 4 hours at

the hyperaemic bone. In infected bone, the uptake would last longer than 24 hours.

False negative can be due to previous antibiotic treatment or transition period from

the cold to the hot phase.

Predictive value of cold scan is higher (100%) as compared to hot scan (82%)

in acute osteomyelitis (Tuson and Hoffman, 1994). Cold scan are due to local

ischaemia due to increased intraosseous and subperiosteal pressure. Patient with

clinical findings of osteomyelitis with positive cold scan can safely be diagnosed as

osteomyelitis. Osteomyelitis in bone scan shows uneven distribution of uptake in the

joint with extensive and asymmetrical involvement beyond the joint. Cold scan

indicate severe infection and also associates with severe systemic presentation (Scott

7

et al, 1990). High positive results bone aspiration from cold spot as compared to the

hot spots on the bone scan (Pennington et al, 1999). Cold scan however can present in

leukamia, metastatic bone disease, avascular necrosis or sickle cell disease.

Ultrasound

The early clinical signs may be minimal, non-specific and difficult to elicit in

an uncooperative child. The primary lesion of osteomyelitis is within the bone, but the

surrounding soft tissues are very soon involved. Ultrasound cannot penetrate dense

bone but it can show early changes in the tissues.

In children with osteomyelitis there were characteristic ultrasound findings

(Howard, 1993): -

1. thickening of the periosteum, with hypo echogenic zones both superficial

and deep to it, giving the appearance of a ‘sandwich’.

2. elevation of the periosteum by more than 2mm ; in severe cases there

were both echoless and moderately echogenic zones between the

periosteum and the cortex

3. swelling of the overlying muscle or subcutaneous tissue, maximal

nearest to the bone

Magnetic Resonance Imaging (MRI)

In the early stage of osteomyelitis the MRI will show intraosseous and

extraosseous changes. These changes are evident before any that may be seen on

routine x-ray films (Aprin, 1988). In osteomyelitis, the typical finding is a low signal

on T1 images and high intensity signal in T2 images. These findings are due to

increased water content in the marrow due to oedema, hyperaemia and purulent

exudative characteristics of osteomyelitis (Tachdjian, 1990).

8

TREATMENT

Surgery or antibiotic treatment for acute hematogenous osteomyelitis is

complimentary, in some patients antibiotic alone will cure the disease but in others

prolonged antibiotic alone is doomed to failure without surgical treatment (Warner,

1991).

Nade (1983) proposed the following five principles for treatment of

osteomyelitis: -

1. an appropriate antibiotic will be effective before the pus formation.

2. antibiotic will not sterilize avascular tissues and purulent material that

must be removed surgically.

3. if such removal is effective, then antibiotics should prevent their

reformation primary wound closure should be safe.

4. surgery should not further damage already damage bone, pus removal

allows restoration of continuity between periosteum and cortex and

restores blood flow.

5. antibiotics should be continued after surgery.

It is reasonable to start the treatment with a combination of antibiotics active

against Staph. aureus and also beta-hemolytic Steptococcus. When the organism is

identified and antibiotic sensitivity is determined, treatment can be continued with a

single appropriate drug (Cole, 1982 and Scoles, 1984). The combination of cloxacillin

and penicillin has been recommended by several authorities (Nade, 1883 and Cole,

1982) and others advocated a combination of sodium fusidate and erythromycin.

Sodium fusidate and erythromycin are drugs of low toxicity, show synergism and

broaden the range of antibiotic coverage (for instance, to include Haemophilus)

(Nade, 1983).

The duration of the antibiotic therapy is controversial. The current trend is

toward a short course intravenous antibiotics, followed by oral antibiotic and

9

monitoring of serum antibiotic levels. Trueta (1968) recommended prolonged

antibiotic treatment of patients with acute osteomyelitis, for example, six weeks of

full dosage because inadequate duration of treatment appears to be empirical by some

authors, they recommended that after 10 days it would be reasonable to discontinue

antibiotic therapy if the clinical signs had subsided, the ESR was normal or falling,

and a radiograph showed only local osteoporosis without erosion of the cortex or new

bone formation (Nade, 1983). In general, four to six week of effective antimicrobial

therapy is required for successful treatment of childhood osteomyelitis.

Oral therapy may be used if the following criteria are met (Scoles, 1984):

1. clinical response to parenteral antibiotic therapy

2. isolation of a bacterial pathogen that is susceptible to orally

administrated antibiotics.

3. patient tolerance of an orally administered agent

4. adequate serum bactericidal activity on oral therapy (peak serum

bactericidal titer greater than 1: 8, trough titer greater than 1:2).

5. ensurance of patient compliance with drug therapy, usually by

hospitalization

In the early stage of disease, successful response to the treatment is seen

within 24 to 36 hours, with a dramatic fall in temperature and improvement in the

local signs. The white blood cell count falls rapidly provided these is no abscess. The

ESR will probably decline slowly, and return of function in the infected limb is a

good sign of positive response.

Conservative treatment with antibiotics has equeal results with surgical

treatment in subacute osteomyelitis with benign radiological findings. Surgery withy

open surgical debridement should be reserved in patients who do not respond to

antibiotics or radiological features of an aggressive disease or malignant tumour

(Reggie et al, 1996).

10

During treatment the affected limb is immobilized to diminish pain,

occasionally some form of the skin traction is required. Protective splintage is

continued in the upper limb until antibiotic therapy is terminated.

Failure to response to treatment after 36 hours probably means that pus is

present in the metaphysis and possibly in the subperiosteal region. Surgical drainage

of any intramedullary or subperiosteum abscess is required in these patients without

further delay.

Two main indications for surgery in the acute hemtogenous osteomyelitis are

(Warner, 1991): -

1. the presence of an abscess requiring drainage.

2. failure of the patient to improve despite appropriate intravenous

antibiotic treatment.

The bone is exposed at the side of maximum tenderness and swelling, and the

periosteum is incised longitudinally. Pus is evacuated and specimens are obtained for

a gram stain, cultures and tests for antibiotic sensitivity. The objective of the surgery

is to drain any abscess cavity and remove all dead or necrotic material, and if a

subperiosteal abscess is found, several small holes should be drilled through the

cortex into medullary canal. If intramedullary pus is found, then a small window of

bone is removed, the pus is drained, and the necrotic tissue is gently removed

(Warner, 1991). Some authors do not recommend drilling the cortex to explore the

metaphysis in view that pus under pressure is rarely found inside the medulla (Cole,

1982).

They believe that the concept of decompressing the medulla and improving

the blood flow is unlikely to be of much benefit since bone death has already occurred

in the presence of a large subperiosteal abscess. It is, however, worthwhile drilling

any obviously soft tissue areas in the cortex (Aprin, 1988)

11

The wound may be loosely closed but provision made for free drainage

through appropriate surgical drains. The value of closed suction drainage with

continous intramedullary irrigation remains to be proved (Aprin, 1988).

PROGNOSIS AND COMPLICATION

Acute hematogenous osteomyelitis is curable provided there is early diagnosis

and prompt treatment with the correct antibiotic for the correct period of time (April,

1988).

The chance of cure is directly related to the following five factors (Nade,

1983): -

1. the virulence of the organism causing the infection, and the resistance of

the host to the spread of the infection.

2. the choice of the antibiotics used initially – these should be the

bactericidal antibiotics most appropriate in treating staphylococcal

infections, given parenterally in adequate dosage.

3. the site of infection.

4. the duration of treatment with antibiotics.

5. a short interval between onset of symptoms and institution of correct

therapy.

Cold spot on bone scan in children with a painful, inflammed limb gives a

poorer prognosis because of the more aggressive nature of infection it associates with

(Pennigton et al ,1999).

Cole and co-workers observed that the prognosis for cure is much worse in

patients diagnosed late (25%) than in patients diagnosed early, in whom the cure rate

was 92% in their series (Cole, 1982). The risk of recurrence is below 4% after one

year following treatment (Gillespie, 1981). Involvement of an adjacent joint is

common in neonate because of the anatomy of the vasculature of this age group and

the intracapsular position of the physis. This causes irreversible damage to the physis

12

and joint. Damaged to the physis can result in overgrowth or growth retardation

leading to the leg length discrepancy and angular deformity (Aprin, 1988).

Pathological fracture may be caused by resorption of bone either in the acute

phase or following surgery and decompression by drill holes through the cortex.

Preventive splint or cast for an appropriate period of 2 to 3 months is indicated.

REFERENCES

1. Abiri MM., Kirpekar M. and Ablow RC. : Osteomyelitis : Detection with

US. Radiology (1989), 172: 509-511

2. Akbar Bonakdar-pour and Gaines VD. : The radiology of osteomyelitis.

Clin. Orthop. (1983), 14: 21

3. Aprin H. and Dee R. : Bone and joint infections. Principles of Orthopaedic

Practice. McGraw-Hill Book Co. (1988), Chap 22: 294-316

4. Cole WD., Dalziel RE. and Leitl S.: Treatment of acute osteomyelitis in

children. J.Bone and Joint Surg. (1982), 64B: 218-223

5. Gillespie WJ. and Mayo KM. : The management of acute haematogenous

osteomyelitis in the antibiotics era: A study of outcome. J.Bone and Joint

Surg. (1981), 63B: 126-131

6. Howard C.B , Einhorn M,Dagan R,Yagupski P : Fine neddle bone biopsy

to diagnose osteomyelitis. J Bone Joint Surg 1994,76 B:311-4.

7. Faden H. and Grossi M. : Acute osteomyelitis in children. Reassessment of

the etiologic agents and their clinical characteristics. Am. J. Dis. Child.

(1991), 145: 65-69

13

8. Howard CB., Einhorn E., Dagan R. and Nyska M. : Ultrasound in

diagnosis and management of acute haemogenous osteomylitis in children.

J.Bone and Joint Surg. (1993), 75B: 79-82

9. Kallio L.U, Kallio M.J.T, Eskola J : Serum Creactive protein,Erythrocyte

Sedimentation Rate and White Blood Cell Count in Acute Haemetogenous

Osteomyelitis of children.Paediatric 93:59-62,1994.

10. Morrissy RT. And Haynes Dw. : Acute hematogenous osteomyelitis : A

model with trauma as an etiology. J.Pediatric Orthop. (1989), 9: 447-456

11. Nade S.: Acute haematogenous osteomyelitis in infancy and childhood. J.

Bone and Joint Surg. (1983), 65B: 109-119

12. O”Brian T , Mc Manus F , Mac Auley PH : Acute haematogenous

osteomyelitis.J Bone Joint Surg 1982 ;64-B:109-19.

13. Ogden JA : Changing patterns of proximal femoral vascularity .J Bone Joint

Surg 1974:56:941-50

14. Patton JT.: Osteomyelitis : Radiological evaluation. Current Orthop. (1988),

2. : 69-75

15. Pennington W.T, Mott M.P, Thometz J.G, Sty J.R : Photophenic bone scan

osteomyelitis :Aclinical prespective. J.Paed.Orthop,1999 19: 695-698.

16. Reggie C.H, Lawton L, Carey T : Subacute haemategenous

osteomyelitis :Are biopsy and surgery always indicated ? J Paeds Orthop

16:220-223,1996

14

17. Scoles PV, Hilty MD. and Sfakianakis GN. : Bone scan patterns in Acute

osteomyelitis. Clin. Orthop. (1980), 153: 210-217

18. Scoles PV. and Aronoff SC. : Current concept review : Antimicrobial therapy

of childhood skeletal infections. J. Bone and Surg. (1984), 66A: 1487-1492

19. Tuazon CU.: Teichoic acid antibodies in osteomyelitis and septic arthritis

caused by Staphylococcus aureus. J.Bone and Joint Surg. (1982), 64A: 762-

765

20. Tuson C.E,Hoffman E.B : Isotope bone scanning for acute osteomyelitis and

septic athritis in children .

21. Warner WC. Jr.: Osteomyelitis. Campbell’s operative orthopaedics, edited

by Crenshaw AH, eight edition. Mosby Year Book. (1991), Chap. 4: 131-150

22. Wedge JH. :. Osteomyelitis: Clinical Presentation. Current Orthop. (1988), 2:

65-68.

15