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Osteomyelitis

Bacterial osteomyelitis (acute)

Authors: Hans Magne Hamnvåg, M.D., Dariusz Borys, M.D.

Editorial Board Member: Nasir Ud Din, M.B.B.S.

Deputy Editor-in-Chief: Borislav A. Alexiev, M.D.

Last author update: 18 July 2022

Last staff update: 18 July 2022

Copyright: 2003-2023, PathologyOutlines.com, Inc.

PubMed Search: Bacterial osteomyelitis [TIAB] acute

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Table of Contents

Cite this page: Hamnvåg HM, Borys D. Bacterial osteomyelitis (acute). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonebacterialosteomyelitis.html. Accessed January 28th, 2023.

Definition / general

Infection involving bone
Rare due to use of antibiotics
Usually pyogenic
Classified based on:
- Mechanism of infection (hematogenous versus nonhematogenous)
- Duration of illness (acute, subacute or chronic) (N Engl J Med 1970;282:198, Infect Dis Clin North Am 2017;31:325, Clin Infect Dis 1997;25:1303, N Engl J Med 1997;336:999)

Essential features

Classified on the basis of duration of illness and mechanism of infection (Infect Dis Clin North Am 2017;31:325, N Engl J Med 1970;282:198, Clin Infect Dis 1997;25:1303, N Engl J Med 1997;336:999)
Due to proliferation of bacteria in bone, causing inflammation and necrosis
Most common infectious agents
- Staphylococcus aureus
- Coagulase negative staphylococci
- Aerobic gram negative bacilli (Clin Infect Dis 2006;42:57)
Diagnosis is established via culture obtained from biopsy of bone, histopathological findings and clinical / radiographic features (Clin Infect Dis 2004;39:885)

Terminology

Osteomyelitis is infection of bone and bone marrow
Synonym: osteitis
Different classifications are based on:
- Duration of the illness
  - Acute osteomyelitis: present with a symptom duration of a few days or weeks
  - Sequestra are absent
  - Chronic osteomyelitis: longstanding infection over months or years
  - Sequestra are usually present (N Engl J Med 1970;282:198, Clin Infect Dis 1997;25:1303, N Engl J Med 1997;336:999)
- Mechanism of infection
  - Hematogenous
  - Direct extension from contiguous site
  - Direct contamination (N Engl J Med 1970;282:198, Clin Infect Dis 1997;25:1303, N Engl J Med 1997;336:999)

ICD coding

ICD-10: M86.9 - osteomyelitis, unspecified

Epidemiology

Hematogenous osteomyelitis
- Occurs most commonly in children
  - More than half occurs in children younger than 5 years and one quarter in children younger than 2 years
  - M > F
- Among adults:
  - Most occur in patients > 50 years (BMC Infect Dis 2010;10:158)
  - M > F
Nonhematogenous osteomyelitis
- Among younger adults: occurs most frequently in the setting of trauma and related surgery
- Among older adults: occurs most frequently as a result of contiguous spread of infection to bone from adjacent soft tissues and joints (diabetic foot wounds or decubitus ulcers) (N Engl J Med 1970;282:198)

Sites

Most common sites in children
- Areas of rapid growth or increased risk of trauma
  - Distal and proximal femur
  - Proximal tibia and humerus
  - Distal radius (Infect Dis Clin North Am 2005;19:787, Adolesc Med State Art Rev 2007;18:79, J Med Assoc Thai 2011;94:S209)
Most common sites for hematogenous osteomyelitis in adults
- Vertebrae (Clin Infect Dis 2015;61:e26)
- Flat bones of the axial skeleton (sternoclavicular and pelvic bones)
Contiguous osteomyelitis
- Occurs in sites predisposed to pressure related skin ulcerations
  - Sacrum
  - Buttock
  - Hips
  - Heels (N Engl J Med 1970;282:198)

Pathophysiology

Bacteria proliferate in bone, cause inflammation and necrosis
Spread along haversian system or medullary cavity within shaft and to periosteum
Subperiosteal abscesses impair blood supply, which causes more necrosis and often draining sinuses
Sequestrum:
- Dead piece of bone
- Gradually separated from living bone by granulation tissue
- May pass through sinus tract
- Avascular and dense on Xray
- Involucrum: sleeve of living tissue created by periosteum, which is deposited around sequestrum (Infect Immun 2016;84:2586)
Hematogenous spread:
- Most common cause
- Usually metaphyseal in children and adults
- Usually long tubular bones of children; involvement of flat bones is more common in adults (Lancet 2004;364:369, N Engl J Med 1997;336:999, N Engl J Med 1970;282:198)
Direct extension:
- Less common
- May be associated with trauma or rarely iatrogenic implantation of infectious material
- In elderly, may affect vertebral column
- May be associated with systemic urinary tract infection, diabetes (affects small bones in feet)
- In younger adults, associated with immunodeficiency or intravenous drug abuse (Lancet 2004;364:369, N Engl J Med 1997;336:999, N Engl J Med 1970;282:198)
Type of bacteria:
- 50% of cases are due to unknown bacteria
- 80% of known cases are due to Staphylococcus aureus, which produces receptors to bone matrix components
- Hematogenous osteomyelitis
  - Usually monomicrobial
  - Staphylococcus aureus is the most common isolated organism (N Engl J Med 1970;282:198, Clin Podiatr Med Surg 1996;13:701, N Engl J Med 1970;282:260, N Engl J Med 1970;282:316)
- All pediatric age groups
  - Most common: Staphylococcus aureus
  - Next most common: group A streptococci, Streptococcus pneumoniae, Kingella kingae (Infect Dis Clin North Am 2005;19:787)
- Neonatal age groups
  - Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli (Pediatr Infect Dis J 1995;14:1047, J Bone Joint Surg Br 1990;72:846)
- Sickle cell patients
  - Salmonella choleraesuis, Salmonella paratyphi B and Salmonella typhimurium (Blood 1995;86:776, J Pediatr Orthop 1992;12:534, Pediatrics 1998;101:296, Int Surg 1998;83:84)
- Intravenous drug addicts (affecting clavicle, sternoclavicular joint, spine or pelvis)
  - Staphylococcus aureus and coagulase negative Staphylococcus (Clin Orthop Relat Res 2010;468:2107)
- Posttraumatic cases: Pseudomonas and mixed bacteria
- Other known organisms are Escherichia coli, Pseudomonas and Klebsiella
- Rarely associated with malakoplaia

Etiology

Hematogenous spread of infectious agents:
- Risk factors
  - Endocarditis
  - Indwelling catheters (vascular catheters, cardiovascular devices)
  - Orthopedic hardware
  - Injection drug use
  - Hemodialysis
  - Sickle cell disease (BMC Infect Dis 2010;10:158, Diagn Microbiol Infect Dis 2017;88:75)
Nonhematogenous spread:
- Direct inoculation
  - Trauma, bite wound, surgery
- Contiguous spread
  - Infection to bone from adjacent soft tissues and joints (diabetic foot wounds, vascular disease, decubitus ulcer) (Lancet 2004;364:369, N Engl J Med 1997;336:999, N Engl J Med 1970;282:198)

Diagrams / tables

Images hosted on other servers:

Pathogenesis of osteomyelitis associated septic arthritis

Clinical features

Signs and symptoms:
- Gradual onset of symptoms over several days
- Dull pain at the involved site
- Tenderness, warmth, erythema and swelling
- Fever and rigors may also be present (N Engl J Med 1970;282:198)

Diagnosis

Diagnosis of osteomyelitis is established via culture obtained from biopsy of the involved bone
Histopathology consistent with osteomyelitis in the absence of positive culture data
Typical clinical and radiographic findings together with persistently elevated inflammatory markers in the absence of positive culture and no biopsy interpretation (Clin Infect Dis 2004;39:885)

Laboratory

Leukocytosis on complete blood count
Elevated inflammatory markers: erythrocyte sedimentation rate (ESR) and C reactive protein (CRP)
Blood cultures are positive in 50 - 60% of cases
Bone aspirate cultures may be positive when blood cultures are negative (N Engl J Med 1970;282:198, Semin Arthritis Rheum 2002;31:271, Clin Orthop Relat Res 1991;264:178)

Radiology description

Conventional radiography:
- Not for early detection of osteomyelitis
- Reasonable initial imaging modality with ≥ 2 weeks of clinical symptoms
- Soft tissue swelling
- Osteopenia
- Cortical loss
- Bony destruction
- Periosteal reaction (Clin Infect Dis 2004;39:885, Arch Intern Med 1994;154:753, AJR Am J Roentgenol 1991;157:365)
Magnetic resonance imaging:
- High sensitivity and negative predictive value
- MRI with no evidence of osteomyelitis after 1 week of clinical signs or symptoms is sufficient for exclusion of osteomyelitis (Infect Dis Clin North Am 2006;20:789)
Late images show prominent periosteal reaction resembling neoplasm (Infect Dis Clin North Am 2006;20:789)
Sclerosing osteomyelitis of Garré:
- Lytic bone destruction surrounded by sclerosis
- Chronic disease may resemble malignant bone tumor due to destructive and regenerative bone changes (J Orthop Surg (Hong Kong) 2019;27:2309499019874704)

Radiology images

Contributed by Mark R. Wick, M.D.

Bacterial osteomyelitis of tibia and vertebra in thoracic spine

Bacterial osteomyelitis of tibia and vertebra in thoracic spine

Images hosted on other servers:

Osteomyelitis of the distal fourth metatarsal

Abnormal T1 weighted signal

Localized increased radioactive tracer uptake

Prognostic factors

Chronic osteomyelitis develops in a subset of acute osteomyelitis due to:
- Delayed treatment
- Inadequate antibiotics
- Incomplete surgical debridement of necrotic bone
- Weakened host defenses (EFORT Open Rev 2017;1:128)

Case reports

28 day old boy with Salmonella osteomyelitis (Ital J Pediatr 2018;44:28)
6 week old girl with brachial plexus palsy with history of osteomyelitis (Pediatr Infect Dis J 2017;36:1219)
37 year old man with Salmonella osteomyelitis (Ulster Med J 2015;84:171)

Treatment

Antibiotic therapy
Surgical debridement
References: Diabetes Care 2015;38:302, Diabetologia 2008;51:962, Infect Dis Clin North Am 2017;31:325

Gross description

Varies with patient age:
- Infants under age 1 year often have permanent joint and epiphyseal damage sparing metaphysis and diaphysis (Arch Pediatr Adolesc Med 1995;149:537)
- Children 1 year and older have opposite changes (sparing of joint, damage to metaphysis) (J Pediatr Orthop 2000;20:40, J Bone Joint Surg Br 2012;94:584)
- Adults have joint infection and extensive bone involvement
Acute disease has pus tracking through bone, periosteal elevation and shell of reactive periosteal bone around necrotic center
Neonates may have considerable subperiosteal spread
Chronic disease is accompanied by prominent periosteal bone formation

Microscopic (histologic) description

Histopathological Osteomyelitis diagnostics (GMS Interdiscip Plast Reconstr Surg DGPW 2014;3:Doc08)

Patterns of acute osteomyelitis

Osseous changes:
- Osteonecrosis: bone trabeculae with visually empty osteocyte cavities are detectable as a criterion for necrotic bone tissue especially with EDTA decalcification
- The bone trabeculae have irregular contours and are fragmented
- They may be fractured and completely necrotic (so called bone sequester)
- There are intramedullary granulocyte infiltrates and fibrin exudates
- In bone tissue with a haemopoietic function (e.g. axial skeleton) there is a reduced or complete lack of haemopoiesis
Soft tissue changes:
- Soft tissue necrosis: criteria for soft tissue necrosis are apoptoses, a tissue eosinophilia, fibrin exudations and a confining texture of the tissue
Inflammatory infiltrate pattern:
- Neutrophilic granulocyte infiltrate: diffuse and grouped deposits (so called microabscesses, ≥ 5 granulocytes) of segmented neutrophilic granulocytes in the usually highly oedematous medullary spaces
- The neutrophilic granulocytes are PAS cytoplasmic, coarsely granular positive and display a plumped, pyknotic chromatin texture (granulocyte apoptosis with pathogen phagocytosis and NETosis)
- Immunohistochemically there is a specific intensive, coarsely granular, predominantly cytoplasmic CD15 positivity
- Osteoclasts are also detectable alongside neutrophilic granulocytes on the irregular trabecular surface

Patterns of chronic osteomyelitis

Osseous changes:
- Bone neogenesis: spongy osseous tissue with reactive network bone neogenesis (POL detection of irregularly running fibrils), the bone surface is bordered by osteoblasts
- Medullary space fibrosis with ectatic sinus
- The medullary space tissue shows fibrosing with granulation tissue formation
- The infiltrate consists of macrophages, lymphocytes, plasma cells and a few neutrophilic granulocytes
Soft tissue changes: there is fibrosing with granulation tissue formation, the infiltrate consists of macrophages, lymphocytes, plasma cells and a few neutrophilic granulocytes
Inflammatory infiltrate pattern:
- Lymphocyte / macrophage / plasma cell infiltrate: in the highly fibrosed medullary spaces there is a lymphocyte and macrophage rich, sometimes also plasma cell rich, sometimes focal, sometimes inflammatory infiltration with a few neutrophilic granulocytes

Neutrophils (may persist for weeks), lymphocytes and plasma cells with bone necrosis and reactive new bone formation
Capillary proliferation and fibrosis
Subtypes include plasma cell osteomyelitis and xanthogranulomatous osteomyelitis (abundant foamy macrophages)
Bone marrow replaced by inflammatory tissue
Salmonella infection may produce tuberculoid granules with variable central necrosis (Am J Surg Pathol 1985;9:531)
Osteoblastic bone resorption
Bitten bone (chewed, scalloped bone)
Bone necrosis
Vessel damage
Vascular thrombosis
Marrow infarction
Dirty marrow (J Foot Ankle Surg 2020;59:75, GMS Interdiscip Plast Reconstr Surg DGPW 2014;3:Doc08)

Microscopic (histologic) images

Contributed by Dariusz Borys, M.D. and Mark R. Wick, M.D.

Acute osteomyelitis

Bacterial acute osteomyelitis

Positive stains

Gram stain

Sample pathology report

Femur, debridement (partial excision):
- Fragments of scalloped viable and non-viable bone with surrounding acute inflammatory infiltrate, consistent with acute osteomyelitis

Differential diagnosis

Lymphoma:
- Monotonous lymphoid infiltrate
- Evidence of monoclonality by immunohistochemistry / molecular findings
Sarcoidosis:
- Noncaseating granulomas
- Disease elsewhere in the body (mediastinum, lung, etc.)
Inflammatory reaction:
- Response to fracture repair with history of trauma
- Not as prominent acute inflammatory infiltrate or dead bone
Osteonecrosis:
- Often chronic process with known history of radiation or medication (bisphosphonate)
Necrosis with subsequent remodeling of bone (Deyrup: Practical Orthopedic Pathology - A Diagnostic Approach, 1st Edition, 2015)

Board review style question #1

Hematogenous osteomyelitis is usually

Monomicrobial and most common organism involved is Staphylococcus aureus
Monomicrobial and most common organism involved is Streptococcus pyogenes
Polymicrobial and most common organism involved is Staphylococcus aureus
Polymicrobial and most common organism involved is Streptococcus agalactiae
Polymicrobial and most common organism involved is Streptococcus pyogenes

Board review style answer #1

B. Monomicrobial and most common organism involved is Streptococcus pyogenes

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Reference: Bacterial osteomyelitis (acute)

Board review style question #2

Most common microbial etiology of bacterial osteomyelitis in neonatal age group is

Salmonella typhi, Staphylococcus aureus, Streptococcus agalactiae
Staphylococcus aureus, Klebsiella, Streptococcus pneumoniae
Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli
Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli

Board review style answer #2

D. Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli

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Reference: Bacterial osteomyelitis (acute)

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