Pathological-Microbiological and clinical approach to Osteomyelitis

1. Bacterial infections of bones and joints
MEHER RIZVI
Associate Professor

2. Objectives
1. Name the bacteria which most commonly cause osteomyelitis and
septic arthritis in adults and children
2. List various routes by which bacteria gain access to bones and joints
3. Describe the pathogenesis of osteomyelitis and septic arthritis
4. Describe the procedures used for establishing laboratory diagnosis of
bone and joint infections

3. • Osteomyelitis: Inflammation of bone and bone marrow due to bacterial infection
• Acute osteomyelitis: 1 in 5000 children
• Chronic osteomyelitis: 2 in 10,000 adults
• Childhood osteomyelitis: long bones of the legs and upper arms.
• Adults osteomyelitis: bones of the vertebrae.
• Types of osteomyelitis:
• Post traumatic osteomyelitis: (47% cases)
• Osteomyelitis due to vascular insufficiency: (34% cases)
• Osteomyelitis due to hematogenous spread: (19%)
• Osteomyelitis post infection of prosthetic joints

4. Pathogenesis
• Bone is normally resistant to bacterial colonization
• Bacteria form a biofilm in the metaphysis (primary focus)
• Biofilms protect bacteria from host immune response
• Abscess in metaphysis
• Subperiosteal abscess
• Sequestrum formation (bone death)
• Involucrum formation (New brittle bone formation)
• Pus perforates periosteum and forms abscess in soft tissues
• Abscess bursts on surface and forms discharging sinus

5. Factors affecting pathogenesis
• Virulence of the infecting organism
• Underlying disease
• Immune status of the host
• Type, location and vascularity of the bone.
Factors that compromise
bone integrity:
• Trauma
• Surgery
• Presence of foreign bodies
• Placement of prostheses
Leads to the onset of bone infection

6. • Signs & Symptoms
• Fever, chills, irritability, fatigue.
• Tenderness, redness, and warmth in the area of the infection.
• Swelling around the affected bone.
• Lost range of motion.
• The symptoms for acute and chronic osteomyelitis are very similar

7. Factors leading to chronic osteomyelitis
 Trauma
 Diabetes
 Prosthetic orthopaedic device
 Peripheral vascular disease
 Chronic joint pain
 i/v drug abuse
 Immunosuppression
 Alcoholism

8. Hematogenous osteomyelitis
• Primary hematogenous osteomyelitis: Most common in infants and
children
• Site: long bone metaphysis.
• Sinus tracts may form if infection extends into soft tissue.
• Secondary hematogenous osteomyelitis:
• Occurs when childhood infection is reactivated.
• Adults:
• Vertebrae: most common, followed by long bones, pelvis, clavicle
• Infections recur and present with minimal constitutional symptoms and
pain.

9. Haematogenous osteomyelitis of tubular bone in child
Blood flow is slow and turbulent and predisposes to bacterial seeding. Lining cells have little or no phagocytic
activity

10. Etiology
Most common:
• Staphylococcus aureus
• Pseudomonas aeruginosa
• Enterobacteriaceae
• Less common organisms:
• anaerobe gram-negative bacilli.

11. • Infants
• Children
• Adults
Streptococcus agalactiae
(Group B Streptococci)
Staphylococcus aureus
Escherichia coli
Staphylococcus aureus
Streptococcus pyogenes
(Group A Streptococci)
Streptococcus pneumoniae
Haemophilus influenzae
CA-MRSA
Staphylococcus aureus
Staphylococcus epidermidis
Pseudomonas aeruginosa
Escherichia coli

12. Etiology associated with certain risk factors:
• Penetrating wound, open fracture: Staphylococcus aureus
• In dwelling prosthetic device: Staphylococcus epidermidis
• Intravenous drug users: Pseudomonal infections.
• Gastrointestinal or genitourinary infections: Escherichia coli & others
• Tooth abscess, gingival disease, dental extraction: Streptococcus viridans
• Mycobacterium tuberculosis: Bone tuberculosis
• Sickle cell disease: Salmonella species in the West
Staphylococcus aureus in Middle East &Africa

13. Acute hematogenous
osteomyelitis
• Symptoms of a severely acute illness. The child is irritable and restless.
• Headache, high-grade fever with chills, tachycardia occurs.
• The affected limb is held in semiflexion, surrounding muscles are in spasm due to
excruciating pain.
• On examination patient resists the passive movement of the affected limb due to
muscle spasm.
• The affected site is tender to deep palpation.
• Initially, swelling is not present but within a few days the soft tissues about the
affected site become edematous and red, indicating subperiosteal abscess
formation.

14. Vertebral osteomyelitis

15. Vertebral osteomyelitis: haematogenous origin
• Source of infection: skin, soft tissue, respiratory tract, genitourinary
tract, infected intravenous sites, and dental infections.
• Complaints: slow progression- 3 weeks to 3 months.
• Localized pain, swelling and tenderness of the involved vertebrae
• Weakness of the vertebral column and surrounding muscles
• Difficulty transitioning from a standing to a sitting position

16. Osteomyelitis in children with sickle cell disease
• Osteomyelitis is the second most common infection in SCD
• Common organisms:
• Salmonella species (Most common in America & Europe)
• S aureus (Most common in Middle East)
• Serratia species
• Proteus mirabilis.

17. Contiguous-focus and posttraumatic osteomyelitis: Adults
Common etiology
Staphylococcus aureus
Staphylococcus epidermidis
Gram negative bacilli
Anaerobes
Nocardia- rare

18. Contiguous-focus and posttraumatic osteomyelitis: Adults
Direct inoculation of bacteria:
• Trauma
• surgical reduction
• internal fixation of fractures
• prosthetic devices
Can spread from:
• soft-tissue infection
• septic arthritis
• nosocomial infection
Vascular compromise: Diabetes
• Infection begins outside the bony cortex
and moves in toward the medullary canal:
Contrast to hematogenous infection
• Low-grade fever, drainage, and pain.
• Most common site: Tibia
• Most common etiology: S aureus

19. Osteomyelitis in diabetes mellitus
• Cause: minor trauma to the feet
• Foot ulcers allow bacteria to reach the bone
• Poor glycaemic control.
Patients may not experience any pain
because of peripheral neuropathy
Presentation: perforating foot ulcer,
cellulitis or an in-grown toenail.
• Etiology: multiple organisms
• Streptococcus species,
• Enterococcus species,
• Staphylococcus aureus
• Staphylococcus epidermidis
• Gram-negative bacilli,
• Anaerobic organisms
(Bacteroides)

20. Skeletal Tuberculosis (Pott’s
Disease)
•Painful bones
•The infected bone will begin to
weaken and become curved
•Absence of feeling and
movement in the diseased bone
•Due to the bone being
weakened, it has a high risk of
being fractured
Tubercular osteomyelitis Pyogenic osteomyelitis
Longstanding history of
months to years
History of days to months
Presence of active pulmonary
tuberculosis
Not present
Most common location:
Thoracic spine
Lumbar spine
> 3 contiguous vertebral
bodies involved
Two vertebrae and
intervening disc
Vertebral collapse : Common
(67%)
Less common (21%)

21. Complications
• Bone death (osteonecrosis). An infection can impede blood circulation within the
bone, leading to bone death.
• Septic arthritis. In some cases, infection within bones can spread into a nearby
joint.
• Impaired growth. In children, the most common location for osteomyelitis is in
the softer areas, called growth plates, at either end of the long bones of the arms
and legs. Normal growth may be interrupted in infected bones.
• Skin cancer. If osteomyelitis has resulted in an open sore that is draining pus, the
surrounding skin is at higher risk of developing squamous cell cancer.

22. In a nutshell

23. Staphylococcus aureus
• Gram positive cocci seen in clusters
• Grows on blood agar: beta hemolysis
• Golden coloured colonies
• Tests:
• Catalase positive
• Coagulase positive
• DNAase positive

25. Virulence markers
• Protein A
• Staphylokinase
• DNAase
• Panton valentine leucocidin: Important virulence factor in CA-MRSA
Forms pores in the membranes of WBCs
• Exfoliative toxin
• Toxic shock syndrome
• Enterotoxins
Superantigens

26. Staphylococcal/ Streptococcal
super-antigens

27. Antimicrobial resistance:
• Penicillin: Drug of choice for Staphylococcus aureus
• Plasmid mediated penicillin resistance: Beta lactamase production
• Methicillin introduced: Resistant to beta lactamase
• Methicillin sensitive Staphylococcus aureus (MSSA)
• Alteration of PBP2a (mec A gene): Methicillin resistant Staphylococcus aureus
(MRSA). Chromosomal mediated methicillin resistance
• Nosocomial MRSA strains (HAMRSA): carried on Staphylococcal cassette
chromosome (SCC) type I-III :
• Drug of choice: Vancomycin, teicoplanin,
• Community acquired MRSA (CAMRSA)- carried on SCC type IV
• More virulent (PVL), Less resistant to antibiotics. Sensitive to clindamycin
Global antimicrobial resistance
1930s
2020s

29. • Vancomycin intermediate Staphylococcus aureus (VISA)
• Vancomycin resistant Staphylococcus aureus (VRSA)
• Antibiotic options:
• Linezolid
• Telavancin
• Daptomycin
• Ceftaroline/Ceftabiprole

30. MRSA: Infection control procedures
• Personnel with active S. aureus lesions and carriers have to be
excluded from patient caring areas
• Eradication of MRSA: Topical application of mupirocin to nasal or
perineal areas
• Patients are screened for MRSA
• Contact precautions: Hand hygiene before and after patient contact
Wearing gloves, gowns etc

33. Pseudomonas aeruginosa
Gram negative, motile bacilli, single polar flagella
Oxidase positive, Strong aerobe
Non fastidious: Grows on Nutrient agar.
Can grow at 420C
Produces various pigments:
pyocyanin, pyoverdin, pyomelanin, pyorubrin
CLED: Non lactose fermenting
Hugh Leifson test
CLED
Blood agar
Nutrient agar

34. Pseudomonas aeruginosa- Ubiquitous saprophytes in nature.
• Classical nosocomial pathogen: moist atmosphere of hospitals:
• Skin & soft tissue infections
• Burn patients: are at risk of septicaemia
• Ecthyma gangrenosum: Acute necrotizing condition in HIV/neutropenic
individuals
• Dermatitis: Papular/vesicular/follicular lesions. Outbreaks in spas/ swimming
pools
• Bone & joints infections
• Septic arthritis
Recall: What other infections?
Other significant infections
• Ventilator associated pneumonia
• Chronic respiratory tract infections
• Cystic fibrosis
• Infective endocarditis in I/V drug
abusers

35. Virulence markers
• Adhesion: Pili/flagella
• Exotoxin A
• Alginate coat: mucoid strains. Produce
biofilms:
• Multidrug resistance
• Multi disinfectant resistance
• Wide temperature range
• Intrinsic resistance to some antibiotics.
• Antipseudomonal drugs:
• Penicillins: Piperacillin, Ticarcillin
• Cephalosporins: Ceftazidime,
cefoperazone, cefepime
• B/BLI: Piperacillin-tazobactam
• Aminoglycosides: Amikacin, tobramycin
• Fluoroquinolones: ciprofloxacin/
levofloxacin
• Carbapenems: imipenem, meropenem
• Polymixin
Antimicrobial resistance

36. Enterococcus spp.
• Gram positive cocci seen mostly in pairs.
• Non fastidious. Hardy
• Catalase negative
• Hemolysis: alpha, beta, gamma
• Bile aesculin test positive:
• Survive extremes of pH, temperature, salinity
• Intrinsic resistance: Cephalosporins & cotrimoxazole
• Low level intrinsic resistance: Penicillins, aminoglycosides
• Penicillin and aminoglycosides
• Vancomycin and aminoglycosides
Intestinal commensal
Synergistic Combination therapy
Species
Enterococcus faecalis
Enterococcus faecium

37. Resistance in Enterococcus
• High level Aminoglycoside Resistance (HLAR): Synergy ineffective
• Vancomycin resistance: Vancomycin resistant enterococci (VRE)
• Mediated by Van gene: Van A-E.
• Van A displays high level resistance
• Alters target site- reduced affinity to vancomycin
• Treatment options: quinupristin-dalfopristin, linezolid, daptomycin,
tigecycline
• Synergistic combination: Ceftaroline & daptomycin
D-alanyl-D-alanine side chain of peptidoglycan
layer is altered to D-alanyl-D- lactate

38. Septic Arthritis: Infection of joint space
Complications:
• Septicemia
• Pre- existing joint disease like rheumatoid arthritis
• Extension of osteomyelitis or other infection near the joint
• Infection subsequent to intra-articular injection, arthroscopy or
orthopaedic surgery- insertion of joint prosthesis

39. Clinical features:
Generally only one joint involved (knee)
Sudden onset
Severe pain
Fever
Swelling and redness of the joint
Causative organism :
S. aureus most common ( as in osteomyelitis )
N. gonorrhoeae
N. meningitidis
Ureaplasma urealyticum

40. Osteomyelitis: diagnosis
Complete medical history
Complete general examination
Complete physical examination
Possible clinical findings
• Pain
• Fever
• Tenderness
• Erythema
• Swelling
• Sinus tract
• Limp

41. Laboratory diagnosis- Osteomyelitis
• Complete blood count
• Elevated WBC count/ Raised CRP/ Raised ESR
• Bone/tissue biopsy/ Fine needle aspirate: Gold standard
• Blood culture: Hematogenous osteomyelitis (60% positivity)
• Wound/Pus culture
• Fluid aspirate from joint (Suppurative arthritis)
• Imaging techniques: CT scan, MRI For confirmation of diagnosis
Serology : Brucella
Molecular methods :
Detection of bacterial DNA in synovial fluid

43. Treatment :
Initial therapy: Empirical antibiotics
High dose parenteral antibiotics 1-2 weeks till fever and symptoms subside
Imipenem; piperacillin-tazobactam; a quinolone plus clindamycin; or an
extended-spectrum cephalosporin plus clindamycin
Specific therapy: 4-6 weeks
De-escalate to oral antibiotics after patient clinically stable
Follow CRP for guidance on duration of treatment

44. Empirical treatment: parenteral
M. tuberculosis: Antitubercular drugs
Anaerobes: Metronidazole or clindamycin
P. aeruginosa : Ciprofloxacin and gentamicin
Escherichia coli : Ciprofloxacin , ceftriaxone
Streptococci : Penicillin, clindamycin
Staphylococcus aureus: Flucloxacillin + gentamicin / clindamycin / fusidic acid

45. Surgical intervention
• Bone death (osteonecrosis): If small sections of dead bone is
infected: bone can heal after surgical removal of small parts of bone.
• If a large section of bone is dead: limb surgically removed (amputated)
to prevent spread of the infection.
• Amputation, limited resection, debridement, and antibiotic therapy
alone each have a place in the management of diabetic foot
osteomyelitis.