Pathology, pathogenesis, general principles of management including principles guiding antibiotic use

1. Principles of
antibiotic use in
management of
Osteomyelitis
Dr Aker Kenneth Ityo FWACS
Consultant Trauma & Orthopaedic Surgeon
Garki Hospital Abuja, Nigeria

2. Introduction
Osteomyelitis, especially the chronic type is a
nightmare to every orthopaedic surgeon
Every action of the orthopaedic surgeon is aimed
toward preventing this disaster or ways of containing
it
Establish osteomyelitis limits all forms of care to
patients

3. Introduction
Nelaton (1834) coined osteomyelitis
The root words osteon (bone) and myelo
(marrow) are combined with itis (inflammation)
to define the clinical state in which bone is
infected with microorganisms

4. Introduction
NB: Acute haematogenous osteomyelitis is mainly
a disease of children
When adults are affected it is usually because
their resistance is lowered
Trauma may determine the site of infection,
possibly by causing a small haematoma or fluid
collection in a bone, in patients with concurrent
bacteraemia

5. Introduction
Epidemiology
Age : Any age group, most common in Infancy &
childhood.
Sex : M:F=4:1
Location : Any part could be involved but
Metaphysis of long bone in children
Poor nutrition, unhygienic surroundings
Highest incidence amongst monozygous forms of
haemoglobinopathies-HBSS, HBSC, etc
4. Blyth MJ, Kincaid R, Craigen MA, Bennet GC. The changing epidemiology of acute and subacute
haematogenous osteomyelitis in children. J Bone Joint Surg Br. 2001;83:99-102.
5.Gillespie WJ. Epidemiology in bone and joint infection. Infect Dis Clin North
Am. 1990;4:361-76.

6. Introduction
Incidence
Scotland decline in incidence from 8.7 per 100.000 in
1970 to 2.9 per 100 000 in 1997
Another Scottish study demonstrated a decline in
incidence of acute haematogenous osteo myelitis in
western European children in recent years, with less
than 3 cases per 100 000 per year
A Lithuanian study a rise in the incidence from 11.5 per
100 000 in 1982 to 14.3 in 2003
Nigerian and African studies are unavailable
Øystein Rolandsen Riise,Eva Kirkhus,Kai Samson Handeland, et al .Childhood osteomyelitis-incidence and
differentiation from other acute onset musculoskeletal features in a population-based study. BMC Pediatrics20088:45
Blyth MJG et al. The changing epidemiology of acute and subacute haematogenous osteomyelitis in
children. J Bone Joint Surg 2001; 83B: 99–102

7. Aetiological Agents
Birth - 1 year
 Staph aureus

E.coli, S. pneumoniae, P.auriginosa, P. mirabilis
1- 16 years
 S. aureus ,
 S. pyogenes
 H. Influenza, Kingella kingae
> 16 years
 S.aureus
 S.epidermidis

8. Aetiological Agents
Anaerobic Bacteria are usually part of mixed infection
Other G-ve organisms (e.g. E. coli, P. aeruginosa, P.
mirabilis & the anaerobic Bacteroides fragilis) occasionally
cause acute bone infection
HBSS -Salmonella typhi

9. Aetiologic Agents: Rare organisms Isolated in
Bacterial Osteomyelitis
Bartonella henselae
Pasteurella multocida or Eikenella
corrodens
Aspergillus species, Mycobacterium
avium-intracellulare or Candida
albicans
Mycobacterium tuberculosis
Brucella species, Coxiella burnetii
(cause of chronic Q fever) or other
fungi found in specific
geographic areas
Human immunodeficiency virus
infection
Human or animal bites
Immunocompromised patients
Populations in which tuberculosis
is prevalent.
Population in which these
pathogens are endemic
Lew DP, Waldvogel FA. Osteomyelitis. N Engl J Med 1997;336:999-1007.

10. Pathoanatomy
<2 years of age, some blood vessels cross the physis &
may allow the spread of infection into the epiphysis
>2 years, the physis effectively acts as a barrier to the
spread of a metaphyseal abscess
Post physeal closure, infection can extend directly
from metaphysis into epiphysis and involve the joint
Septic arthritis resulting from acute hematogenous
osteomyelitis generally is seen only in infants and
adults

11. Pathoanatomy
Metaphysis has relatively fewer phagocytic cells,
allowing infection to occur
Metaphysis cortex is thinner resulting abscess breaks
through forming a subperiosteal abscess

12. Pathoanatomy
Some physes of some joints are intracapsular e.g.
femoral neck, the proximal humerus, radial neck, and
distal fibula also are intraarticular, and infection in
these areas can lead to septic arthritis as well
In severe infection, epiphyseal separation can occur
in children younger than 2 years

13. Pathogenesis /Pathology
Acute Osteomyelitis shows characteristic progression
Inflammation Bone necrosis reactive new
bone formation resolution
Intractable chronicity
Blood stream is invaded from a minor skin abrasion,
treading on a sharp object, an injection point, a boil, a
septic tooth or – in the newborn – from an infected
umbilical cord
In adults the source of infection may be a urethral
catheter, an indwelling arterial line or a dirty needle
and syringe, post op

14. Pathogenesis
In children the infection commences in the
metaphysis
Relative vascular stasis and consequent lowered
oxygen tension favour bacterial colonization
Structure of the fine vessels in the hypertrophic zone
of the physis allows bacteria to pass through and
adhere to type 1 collagen in that area
 Song KM, Sloboda JF Acute haematogenous osteomyelitis in children. J Am Acad Orthop Surg 2001;
9:166-75

15. Pathogenesis
Pre-existing focus / Exogenous Infection
Acute inflammation PMN, exudation of fluid,congestion
Infected thrombus forms & blocks small caliber hairpin
loop vessels(metaphysis)
Vascular congestion from Thrombosis
Increased intraosseous pressure

16. Bacteria enzymes, phagocytes, Cytokines, GF, PG,
osteoclastic activity leads to demineralization
debris & intramedullary
pressure
Pus formation within bone

17. Pus follows paths of least resistance
Passes through Haversian canal and Volkmann canal
Subperiosteal abscess
Local cortical necrosis
Pus spreads to shaft
Re-enter bone at another level
or bursts to surrounding tissues
or burst through joint capsule

18. granulation tissues forms undrneath stripped periosteum
Underlying bone is sequestered and appears by end of 1st
week

19. Development of Osteomyelitis

20. Clinical features
Varies with age
Fever
Chills
Fatigue
Lethargy
Irritability
Classic signs of inflammation as defined by first
century AD Roman scholar Celsus viz: tumor, calor,
dolor, rubor and functio laesa the 5th
sign of
inflammation added by Galen may also occur &
normally disappear within 5-7 days

21. Clinical features
Haemoglobinopathy, trauma, sepsis, surgery, past
history of trauma & previous antibiotic

22. Clinical features
Physical Examination
SWD
Note cardinal signs of inflammation
ROM

23. Clinical features
Children
Clinical presentation can be challenging & extremely
variable
Nonspecific signs & symptoms
Decreased movement & pain in the affected
limb/adjacent joint
Oedema & erythema over the involved area
Fever, malaise, & irritability
Newborns with osteomyelitis may demonstrate
decreased movement of a limb without any other
symptoms /signs

24. Clinical features
Sympathetic synovitis with joint effusion with
sterile clear fluid
Note that metaphysis in lies within the joint
capsule of the hip, shoulder, ankle. Therefore
these joints can develop septic arthritis by
extension of osteomyelitis

25. Differential Diagnosis
 Cellulitis Cellulitis:
 Organism is usually staphylococcus or streptococcus
 widespread superficial redness and lymphangitis
 MRI will help to distinguish between bone infection
and soft-tissue infection
 Mild cases will respond to high dosage oral
antibiotics
 severe cases need intravenous antibiotic treatment.

26. Differential Diagnosis
 Acute suppurative arthritis:
 Diffuse tenderness restriction of ROM by muscle
spasm
 In infants the distinction between metaphyseal
osteomyelitis & septic arthritis of the adjacent joint is
theoretical, as both often coexist
 A progressive rise in C-reactive protein values over
24–48 hours is said to be suggestive of concurrent
septic arthritis (Unkila-Kallis et al., 1994)

27. Differential Diagnosis
 Streptococcal necrotizing myositis:
 Group A betahaemolytic streptococci occasionally
invade muscles and cause an acute myositis which, in
its early stages, may be mistaken for cellulitis or
osteomyelitis
 Rare but usually rapidly progresses towards muscle
necrosis, septicaemia & death
 Medical emergency

28. Differential Diagnosis
 Streptococcal necrotizing myositis:
 Intense pain & board-like swelling of the limb in a
patient with fever and a general feeling of illness
 Confirmation of diagnosis by MRI - muscle swelling
and possibly signs of tissue breakdown
 Immediate treatment with intravenous antibiotics is
essential
 Treatment: Debridement or even amputation

29. Differential Diagnosis
 Sickle-cell crisis: Features indistinguishable
from those of acute osteomyelitis
 Gaucher’s disease: ‘Pseudo-osteitis’ may
 Features closely resembling those of osteomyelitis
 The diagnosis is made by finding other stigmata of
the disease, especially enlargement of the spleen and
liver

30. Investigations
Laboratory
FBC Leucocytosis rarely exceeds 15,000/µL
Anaemia
ESR & CRP Elevated
Blood cultures positive in only 50% They should be
obtained before or at least 48 hours after antibiotic
treatment
Bone biopsy- before the initiation of antibiotics or more
than 48 hours after discontinuance definitive diagnosis
by isolation of pathogens

31. Investigations
X Rays
Must include contralateral normal limb for comparison
Normal findings in 1st
2 weeks & of no help in diagnosis
X ray appearance indicates chronic stage/complication
It takes from 10 to 21 days for an osseous lesion to
become visible on conventional radiography, because a
30–50% reduction of bone density must occur before
radiographic change is apparent

32. Investigations
X Rays
Findings include:
1. Localized osteopaenia & trabecular destruction are early
signs of a suppurative acute process in the bone
2. Wide spectrum of cortical destruction ranging from a
solitary radiolucency to irregular, multiple
radiolucencies (mottling) to a permeative pattern
3. Lamellated periosteal reactions are invariably present

33. Investigations
X Rays
Findings include:
5. Endosteal & periosteal new bone formation,
development of surrounding sclerosis and sometimes
large osteosclerotic areas
6. Soft tissue changes, such as swelling and obliteration
of tissue planes in children

34. Investigations
X Rays
Findings include:
7. In newborns and infants, loss of normal fat planes in
acute phase indicative of soft tissue swelling.
Lamellated periosteal changes are generally discernible
in this age group
8. Ballooned metaphysis in new born could involve of the
epiphysis

35. Investigations
USS
 Indirect assessment by identifying periosseous soft
tissue abnormalities
 Oedematous swelling of the deep soft tissues 1st
USS
findings
Cardinal E, Bureau NJ, Aubin B, Chhem RK (2001) Role of ultrasound in muskuloskeletal infections. Radiol Clin
North Am 39:191–201

36. Investigations
CT Scan
Provides specific anatomic information on
status of infection
Sequestra (indicative of chronic osteomyelitis)
Intra-osseous gas
Can define subperiosteal abscesses
MRI
 Goal standard
 Very high sensitivity and specificity

37. Investigations
Radioisotope scanning
Highly specific
Diagnostic in 1st
48 hours with accuracy level of 92%
Bone scan
revealing hot spot
in right tibia
1.“The Accuracy of Diagnostic Imaging for the Assessment of ChronicOsteomyelitis: A Systematic Review and
Meta-Analysis” The Journal of Bone and Joint Surgery (American). 2005;87:2464- 2471.
2. “FDG PET/CT imaging in the diagnosis of osteomyelitis in the diabetic foot” Kagna O, Srour S Eur J Nucl
Med Mol Imaging. 2012 Jul 17

38. Diagnostic Criteria
1. Severe acute illness, rapid onset & toxemia
2. Local severe pain & unwillingness to move limbs
3. Deep tenderness
4. WBC count ≥ 20,000
5. Bacterial culture & sensitivity to antibiotics
6. Tc99m scaning
7. MRI rather than planar bone scintigraphy

39. Diagnostic Criteria
Morrey & Peterson’s Criteria
 Definitive- Pathogen is isolated from bone or
adjacent soft tissue as there is histologic
evidence of osteomyelitis
 Probable- a blood culture is positive in setting
of clinical & radiological features of
osteomyelitis
 Likely- typical clinical finding & definite
radiographic evidence of osteomyelitis are
present and response to antibiotic therapy
Morrey, B.- F. & Peterson, H. A. (1975) Hematogenous pyogenic osteomyelitis in children. Orthop. Clin. N.
Amer. 6, 935-951.

40. Diagnostic Criteria
Peltola and vahvanen’s criteria
 Pus on aspiration
 Positive bacterial culture from bone or blood
 Presence of classic signs and symptoms of acute
osteomyelitis
 Radiographic changes typical of osteomyelitis
*--Two of the listed findings must be present for establishment of the
diagnosis
Peltola H, Vahvanen V (1984) A comparative study of osteomyelitis and purulent arthritis with special reference to
aetiology and recovery. Infection 12:75–79

41. Treatment
Principle
Acute Osteomyelitis is an emergency
Once diagnosis of acute osteomyelitis is made, the
patient should be admitted for parenteral
administration of antibiotics and other supportive care
 Surgery & antibiotic treatment are complementary
In some patients antibiotic treatment alone cures the
disease; in others, prolonged antibiotic treatment is
doomed to failure without surgical treatment

42. Treatment
The choice of antibiotic is based on the highest
bactericidal activity, the least toxicity, and the most
affordable
A combination of broad spectrum antibiotics covering
Gram negative, Gram Positive and Anaerobes should be
chosen empirically
Established sequestered abscesses demand surgical
drainage
Areas of simple inflammation without abscess
formation can be treated with antibiotics alone

43. Treatment
Nade’s principles: In 1983, Nade proposed five
principles for the treatment of acute hematogenous
osteomyelitis that are still applicable today
1. Antibiotics are effective before pus forms
2. Antibiotics cannot sterilize avacular tissue
3. Antibiotics prevents reformation of pus once removed
4. Pus removal restores periosteum---- restores blood flow
5. Antibiotics should be continued after surgery
Nade S. Antibiotics in the management of acute haematogenous osteomyelitis and acute septic arthritis in infancy
and childhood. Aust New Zealand J Surg. 1978;48:78–80

44. Treatment algorithm of
long-bone osteomyelitis
Osteomyelitis in long bones, L .
Lazzarini,J.T.Mader,JBJS.Am.2004;86:2305-2318

45. Treatment
Once osteomyelitis is suspected on clinical grounds,
blood and fluid samples should be taken for
laboratory investigation and then treatment started
immediately without waiting for final confirmation
of the diagnosis
Four important aspects to the management
1. Supportive treatment for pain & dehydration.
2.Splintage of the affected part
3. Appropriate antimicrobial therapy
4.Surgical drainage

46. Treatment
General Supportive Treatment
Distressed child needs to be comforted
Control pain- Analgesics at repeated intervals without
waiting for the patient to ask
Septicaemia and fever can cause severe dehydration
and it may be necessary to give fluid intravenously

47. Treatment
Splintage
Splint for comfort
Prevent joint contractures
Simple skin traction may suffice and, if the hip is
involved, this also helps to prevent septic dislocation
Other sites a plaster slab or half-cylinder may be used
but it should not obscure the affected area

48. Treatment
Antibiotics:
Sample collection
Prompt IV antibiotics
Do not await result
Empirical Antibiotic: clinician’s experience of local
conditions ‘best guess’
Broad spectrum Antibiotic with good bone penetration
can be substituted, after MCS

49. Treatment
Consider factors such as:
 the patient’s age
 general state of resistance
 renal function
 degree of toxaemia
 previous history of allergy

50. Treatment
The following recommendations are offered as a
guide
Neonates -6 months: AB should target penicillin-
resistant S. aureus, Group B streptococcus & Gram-
negative organisms
Fucloxacillin +3rd-gen cephalosporin eg cefotaxime
Alt. Combination of flucloxacillin (for penicillin-
resistant staphylococci), benzylpenicillin (for Group B
streptococci) and gentamicin (for Gram-negative
organisms)
6 months - 6 years: cover against Haemophilus
influenzae
Fucloxacillin & cefotaxime or cefuroxime

51. Treatment
The following recommendations are offered as a
guide
>6years +previously fit adults: IV Flucloxacillin and
fusidic acid.
Allergic patient to penicillin should be treated with a 2nd
or 3rd
generation cephalosporin
Elderly and previously unfit patients: Greater than
usual risk of Gram-negative infections
Flucloxacillin +2nd
or 3rd-gen. cephalosporin

52. Treatment
HBSS: Prone to staphylococcal infection &
salmonella &/or other Gram-negative
organisms
3rd
gen. cephalosporin or a fluoroquinolone like
ciprofloxacin
Heroin addicts and immunocompromised
patients Unusual infections: Empirically with
a broad-spectrum antibiotic 3rd
gen. ceph or a
fluoroquinolone preparation
Risk of meticillin-resistant Staphylococcus aureus
(MRSA) infection:IV vancomycin (or similar
antibiotic) + 3rd
Gen ceph

53. Treatment
IV Drugs until
Patient’s condition begins to improve
CRP values return to normal levels -2–4 weeks
Monitor CRP, ESR and WBC values

54. Treatment
Drainage: Nade’s indication for surgery
Drain pus, little to be gained by drilling into the
medullary cavity
No obvious abscess, it is reasonable to drill a few holes
into the bone in various directions
Cortical window if large abscess
Close wound without drain & splint
Once the signs of infection subside, movements are
encouraged and the child is allowed to walk with the
aid of crutches
Full weightbearing is usually possible after 3–4 weeks

55. Nade’s indications for surgery
1. Abscess formation
2. Severely ill & moribund child with features of acute
osteomyelitis
3. Failure to respond to IV antibiotics for >48 hrs
Nade S. Antibiotics in the management of acute haematogenous osteomyelitis and acute septic arthritis in infancy
and childhood. Aust New Zealand J Surg. 1978;48:78–80

56. Complication
A lethal outcome from septicaemia is nowadays
extremely rare
But morbidity is common, especially if treatment is
delayed or the organism is insensitive to the chosen
antibiotic
1. Epiphyseal damage and altered bone growth:
Neonates & infants
At the hip joint, the proximal end of the femur may
be so badly damaged as to result in a pseudarthrosis.
Ramos OM: Chronic osteomylitis in children. Paedi Infe Dis J 2002; 21:431

57. Complication
2. Suppurative arthritis This may occur:
i. In very young infants, in whom the growth disc is not
an impenetrable barrier
ii. where the metaphysis is intracapsular, as in the upper
femur
iii. From metastatic infection. In infants it is so common
as almost to be taken for granted, especially with
osteomyelitis of the femoral neck. Ultrasound will
help to demonstrate an effusion, but the definitive
diagnosis is given by joint aspiration.
Ramos OM: Chronic osteomylitis in children. Paedi Infe Dis J 2002; 21:431

58. Complication
2. Metastatic infection: Involve other bones, joints,
serous cavities, the brain or lung
Infection may be multifocal from the outset
Easy to miss
Be alert to this complication and to examine the
child all over and repeatedly
3. Pathological fracture: Uncommon
May occur if treatment is delayed & bone is
weakened either by erosion at the site of infection
or by overzealous debridement
Ramos OM: Chronic osteomylitis in children. Paedi Infe Dis J 2002; 21:431

59. Complication
4. Chronic osteomyelitis: Despite improved
methods of diagnosis and treatment, acute
osteomyelitis sometimes fails to resolve
May be due to late or inadequate treatment but is
also seen in debilitated patients and in those with
compromised defence mechanisms
Ramos OM: Chronic osteomylitis in children. Paedi Infe Dis J 2002; 21:431

60. Thank You