Overview
This lecture covers the two main musculoskeletal infections, Osteomyelitis and Septic arthritis: their aetiology and risk factors, how routes of infection differ by age and mechanism, the clinical presentation and complications, the pathogenesis of chronic disease, and how each is diagnosed and treated.
Osteomyelitis: definition, classification and routes of infection
- Osteomyelitis is an inflammatory process of bone secondary to bacterial infection; it may involve the periosteum, medullary cavity, and compact or cancellous bone.
- Classified three ways:
- Duration: acute, subacute, chronic
- Route of infection: haematogenous, exogenous
- Host response: pyogenic, granulomatous
- Routes of infection:
- Haematogenous: most common in children, due to vascular stasis at the growth plates; accounts for 20% of adult cases; usually monomicrobial
- Exogenous, direct: inoculation of bone by trauma (open fracture) or surgery, typically in adolescents/young adults
- Exogenous, contiguous: spread from a local infection, typically in older adults, especially the feet in diabetics; often polymicrobial
Osteomyelitis: aetiology and risk factors
- Haematogenous aetiology by age:
- Neonates (premature): S. aureus, S. agalactiae, E. coli
- Children/adolescents: S. aureus, S. pyogenes, S. pneumoniae, E. coli
- Adults: S. aureus, streptococci/enterococci, gram-negatives
- Monomicrobial
- Exogenous (direct inoculation/contiguous) aetiology: S. aureus, streptococci/enterococci, gram-negatives (Pseudomonas, E. coli), obligate anaerobes; often polymicrobial
- S. aureus causes 90% of infections in children and 30-50% in adults
- Risk factors: immunosuppression (diabetes, steroids, cancer, asplenia), age (children and elderly), peripheral vascular disease (diabetes, smoking), IV drug use, chronic joint disease, recent bone surgery/joint replacement/bone trauma
Osteomyelitis: clinical features, pathogenesis and complications
- Children: metaphysis of long bones most commonly affected, with severe pain, oedema, erythema, pseudoparalysis, and fever/malaise/nausea/vomiting; infants have less dramatic symptoms
- Adults: haematogenous disease has a less acute onset; spine/pelvis affected in those over 45 years, presenting with backache; contiguous disease affects diabetics’ feet
- Site by population: metaphysis of long bones most common in children; foot bones most common in adult diabetics; vertebrae and pelvis are other adult sites
- Pathogenesis (sequence): inflammation causes increased pressure and vascular congestion, leading to ischaemia and necrosis and osteolysis; suppuration produces pus in bone, with sinus formation in chronic infection; a sequestrum forms (a focus of devitalized bone); an involucrum forms during healing (new bone formation, which may occur over the sequestrum, becoming a focus of infection/biofilm and giving rise to chronic or recurrent disease); the process then resolves or progresses to complication
- Complications: septic arthritis, DVT, sepsis, metastatic infection, chronic/recurrent osteomyelitis, altered bone growth, pathological fracture
Osteomyelitis: diagnosis
- Aspiration of pus from bone, performed before starting antimicrobial therapy
- Gram stain: directs empiric antimicrobial choice; Gram-positive cocci in clusters indicates S. aureus, treated with flucloxacillin
- Culture: around 25% of cases are culture-negative
- Bone biopsy: H&E histology and culture
- Blood culture: positive in around 50% of haematogenous osteomyelitis
- Clinical diagnosis supported by leukocytosis (neutrophilia) and raised CRP
- Imaging: X-rays initially appear normal (take 10-14 days before osseous changes are visible, by which point >50% bone loss has occurred); CT is useful for bones difficult to X-ray (pelvis, vertebrae) but requires disease present for over 1 week; MRI is useful for early diagnosis; bone scans (scintigraphy) use radioactive isotopes such as technetium and are useful in early infection, 48-72 hours after onset
Osteomyelitis: treatment
- Medical: IV empiric broad-spectrum therapy or combinations covering S. aureus, streptococci, Pseudomonas, E. coli
- Flucloxacillin, vancomycin (S. aureus/MRSA/S. epidermidis)
- Penicillin (streptococci)
- Cephalosporins/fluoroquinolones (E. coli)
- Beta-lactam plus beta-lactamase inhibitor, or fluoroquinolone, or carbapenem (Pseudomonas)
- Narrow the spectrum once sensitivities are known
- Duration: 4-6 weeks IV plus 2-4 weeks oral
- Surgical: debridement (generally not needed in children); amputation may be required in diabetics
Subacute and chronic osteomyelitis
- Brodie’s abscess (subacute osteomyelitis): a localised S. aureus abscess with few clinical signs (little to no pain), which may persist for years, with a sinus draining pus or acute osteomyelitis developing
- Diagnosis: aspiration/biopsy of the abscess (around 50% culture positive); X-ray shows a characteristic localised, well-defined lesion in the metaphysis of long bones
- Treatment: long course of antimicrobials plus surgical debridement
- Chronic osteomyelitis: can complicate acute osteomyelitis (the sequestrum acts as a source of infection) or arise de novo (post-surgical, trauma, diabetes)
- Often polymicrobial: S. aureus, S. epidermidis, streptococci, gram-negatives, anaerobes
- Granulomatous forms: TB, syphilis
- Diagnosis: biopsy for culture/staining, and X-ray
- Treatment: long course antimicrobial therapy plus surgical debridement
Septic arthritis: definition, aetiology and risk factors
- Invasion of a joint by an infectious agent causing arthritis; caused by bacteria (most damaging), viruses, or fungi; can be acute or chronic, with a focus here on acute bacterial disease as the most serious and damaging
- Disease is characterised by colonisation of synovial fluid, influx of inflammatory and immune cells, effusion in the joint space, and erosion of the synovial membrane
- Acute bacterial aetiology:
- 60-80% S. aureus
- S. epidermidis/streptococci/enterococci
- Neisseria gonorrhoeae following an STI, accounting for 75% of cases in younger sexually active people (US)
- Gram-negatives (E. coli, Pseudomonas) in the immunocompromised/elderly/IV drug users
- Less commonly, polymicrobial/anaerobic infection following trauma or metastatic infection
- Prosthetic joint infection has an increasing incidence with joint surgery/replacement:
- Early onset (<3 months post-implant): S. aureus, forming biofilms
- Late onset (3-24 months post-implant): S. epidermidis, forming biofilms; treated as S. aureus (flucloxacillin) but with methicillin resistance possible (vancomycin)
-
24 months post-implant: haematogenous spread
- Other risk factors: previously damaged joints (RA, OA, SLE, gout) through existing inflammation and damage to defence mechanisms, joint replacement surgery, IV drug use, immunosuppression, male sex (56% of infections), and age (around 50% of infections occur in people over 65 years)
Septic arthritis: clinical features and routes of entry
- Acute onset of inflammation and swelling causing joint effusion, with loss of joint mobility (pseudoparalysis) and arthralgia
- Site distribution: knee 40-50% (most common site in adults), hip 20-25% (most common site in children), ankle/shoulder/wrist/elbow/fingers 10-15%
- Monoarticular in 80% of cases; polyarticular disease is associated with S. aureus and Neisseria
- Few systemic signs; fever is low grade or absent
- Routes of entry: direct inoculation (surgery, trauma, IV drug use); infection of periarticular tissues via contiguous spread from local osteomyelitis; haematogenous spread from wounds/abscesses, the mouth/teeth, or respiratory/GI/urogenital tract infections
- Complications: sepsis, osteomyelitis, joint destruction
Septic arthritis: diagnosis
- Aspiration of synovial fluid (arthrocentesis): not practical if the joint is deep or has a small synovial space; aspirate typically appears turbid, yellow, with decreased viscosity
- Gram stain: directs empiric antimicrobials
- Culture: usually positive in non-Neisseria cases unless antibiotics have already been given; only 25% of gonococcal cases are culture positive
- Blood culture: positive in around 50% of S. aureus cases
- Imaging: X-ray, ultrasound
Septic arthritis: treatment
- Rapid treatment is required because the infection is destructive
- Medical treatment is similar to osteomyelitis: IV empirical therapy, changed once sensitivities are known
- S. aureus: flucloxacillin
- MRSA/S. epidermidis: vancomycin
- Neisseria gonorrhoeae/gram-negatives: cephalosporin
- Duration: 2-4 weeks IV plus 1-2 weeks oral
- Surgical: aspiration/drainage of infected synovial fluid (not required for N. gonorrhoeae); removal of infected prosthesis/debridement may be required
Self-test
- Define osteomyelitis and list the three ways it is classified.
- Distinguish the haematogenous and exogenous routes of osteomyelitis, including which age groups each typically affects and whether each is usually monomicrobial or polymicrobial.
- Describe the steps of the pathogenesis of chronic osteomyelitis, from initial inflammation through to sequestrum and involucrum formation.
- A 6-year-old presents with severe pain, oedema and erythema over the distal femur, with fever and vomiting. What is the most likely diagnosis, the most likely site involved, and the most likely causative organism?
- What proportion of osteomyelitis cases are culture-negative, and what proportion of haematogenous cases have positive blood cultures?
- Why do X-rays often appear normal early in osteomyelitis, and which two imaging modalities are preferred for early diagnosis?
- What is the recommended duration and route of antimicrobial therapy for osteomyelitis, and which agents are used for S. aureus, MRSA, streptococci, E. coli and Pseudomonas respectively?
- Describe a Brodie’s abscess: what it is, why it is easily missed clinically, and how it is diagnosed and treated.
- List the causes of septic arthritis by pathogen type, and give the approximate proportion caused by S. aureus.
- Distinguish early-onset from late-onset prosthetic joint infection in terms of timing and causative organism.
- List the three routes of entry for septic arthritis, with an example source of infection for each.
- Why is rapid treatment of septic arthritis particularly important, and what is the recommended duration and route of antimicrobial therapy?
- A young sexually active patient presents with joint pain. Which organism should be specifically considered, and what feature of that organism’s culture behaviour affects diagnosis?
- Explain how osteomyelitis and septic arthritis can each lead to the other as a complication.
Answers
Reveal answers
- Osteomyelitis is an inflammatory process of bone secondary to bacterial infection. It is classified by duration (acute, subacute, chronic), route of infection (haematogenous, exogenous), and host response (pyogenic, granulomatous).
- Haematogenous osteomyelitis is most common in children (due to vascular stasis at growth plates) and is usually monomicrobial; it accounts for only 20% of adult cases. Exogenous osteomyelitis arises by direct inoculation (trauma, surgery), typically in adolescents/young adults, or by contiguous spread, typically in older adults (e.g. diabetic feet); exogenous infection is often polymicrobial.
- Inflammation causes increased pressure and vascular congestion, leading to ischaemia, necrosis and osteolysis. Suppuration produces pus in bone with sinus formation in chronic disease. A sequestrum (focus of devitalized bone) forms. Healing produces an involucrum (new bone formation), which may occur over the sequestrum, becoming a focus of infection/biofilm that drives chronic or recurrent disease. The process then resolves or progresses to complication.
- Acute haematogenous osteomyelitis, most likely at the metaphysis of the long bone (femur), most likely caused by S. aureus (the cause of 90% of childhood cases).
- About 25% of osteomyelitis cases are culture-negative; about 50% of haematogenous cases have positive blood cultures.
- X-rays appear normal early because it takes 10-14 days before osseous changes are visible, by which time over 50% bone loss has occurred. MRI (useful for early diagnosis) and bone scans/scintigraphy (useful 48-72 hours after onset) are preferred for early diagnosis.
- 4-6 weeks IV followed by 2-4 weeks oral therapy, started empirically then narrowed once sensitivities are known. S. aureus: flucloxacillin (vancomycin if MRSA); streptococci: penicillin; E. coli: cephalosporins/fluoroquinolones; Pseudomonas: beta-lactam plus beta-lactamase inhibitor, fluoroquinolone, or carbapenem.
- A Brodie’s abscess is a localised S. aureus abscess causing subacute osteomyelitis. It has few clinical signs (little to no pain) and may persist for years, so it is easily missed. It is diagnosed by aspiration/biopsy (around 50% culture positive) and X-ray showing a characteristic localised, well-defined metaphyseal lesion. Treatment is a long course of antimicrobials plus surgical debridement.
- S. aureus causes 60-80% of acute bacterial septic arthritis. Other causes include S. epidermidis/streptococci/enterococci, Neisseria gonorrhoeae (following STI, 75% of cases in younger sexually active people), and gram-negatives (E. coli, Pseudomonas) in the immunocompromised/elderly/IV drug users.
- Early-onset prosthetic joint infection (<3 months post-implant) is caused by S. aureus forming biofilms. Late-onset infection (3-24 months post-implant) is caused by S. epidermidis forming biofilms.
- Direct inoculation (surgery, trauma, IV drug use); contiguous spread from local osteomyelitis into periarticular tissue; haematogenous spread (from wounds/abscesses, the mouth/teeth, or respiratory/GI/urogenital infections).
- Rapid treatment is needed because septic arthritis is destructive to the joint. Treatment is IV empirical therapy for 2-4 weeks followed by 1-2 weeks oral, changed once sensitivities are known (flucloxacillin for S. aureus, vancomycin for MRSA/S. epidermidis, cephalosporin for Neisseria gonorrhoeae/gram-negatives).
- Neisseria gonorrhoeae should be considered. Culture is positive in only 25% of gonococcal cases, making diagnosis harder than for other organisms.
- Osteomyelitis can spread to an adjacent joint causing septic arthritis (osteomyelitis is a listed complication of septic arthritis via contiguous spread, and septic arthritis is a listed complication of osteomyelitis), since infection can track from a bony focus into the joint capsule or from periarticular structures into the joint space.