WEEK 1: Microbiology of bone and joint infections Flashcards
Define osteomyelitis.
Osteomyelitis – can be defined as an inflammatory process affecting the bone and bone marrow caused by an infectious organism(s) resulting in localised bone destruction, “necrosis” and deposition of new bone.
Osteomyelitis includes a broad array of infections.
State them.
Osteomyelitis includes a broad array of infections i.e.septic arthritis, prosthetic joint infections, osteomyelitis, spinal infections (discitis, vertebral osteomyelitis and epidural abscess) and diabetic foot osteomyelitis.
State the effects of bone and joint infections.
Bone and joint infections cause serious morbidity and pose significant management challenges.
They may cause acute sepsis with bone and joint destruction, chronic pain, discharging wounds and permanent disability.
Untreated, it progresses to necrosis of bone ______________followed by new bone formation ______________.
Untreated, it progresses to necrosis of bone (sequestra) followed by new bone formation (involucrum)
Describe the routes of infection.
- Hematogenous
Via the bloodstream - Contiguous
Transmitted from infection in overlying tissue e.g. Diabetic foot ulcer. - Direct inoculation
Pathogens reach bone directly e.g., penetrating injuries, contamination during surgery e.g. prosthetic joint implants.
NB. Infection in bone may spread to adjacent joint.
Bone and joint infections may also be categorized as ACUTE or CHRONIC.
Define acute and chronic bone infections.
Acute develops over several days or few weeks .Vs.
Chronic continues over months or years, characterized by relapses, persistence of microorganisms, low-grade inflammation, dead bone & fistulous tracts.
Describe the following categories of osteomyelitis.
1. Primary hematogenous spread
2. Contiguous infection
3. Vascular or neurologic insufficiency associated osteomyelitis
Primary hematogenous spread (A+B) of bacteria primarily affects the metaphysis of young growing children. But can also afflict the vertebra across all ages, (NB, osteomyelitis can also affect other locations.
Contiguous infection (C+D) bacterial transmission to the bone from another contaminated site. Commonly occurs as direct contamination by bacteria in open fractures or joint replacement surgery with an orthopedic implant (Periprostheticjoint infection(PJI ).
Vascular or neurologic insufficiency associated osteomyelitis (E)results from poor blood supply e.g. diabetic wounds, loss of protective sensation and altered immune defenses, commonly affecting the lower extremity.
Discuss the risk factors of osteomyelitis.
1.Diabetes
Poorly managed high blood glucose can cause neuropathy, loss of sensation
Diabetic foot ulcers or other feet injuries may go unnoticed
Due to poor circulation, deceased sensation vascular insufficiency, feet infections spread to the bone.
- Immunocompromised patients esp. with assoc. conditions causing poor blood circulation e.g.
peripheral arterial disease, atherosclerosis & type 1 & 2 diabetes - Orthopedic surgery e.g. prosthetic implants
- Use of unsterilised needles e.g. intravenous drug use, increases risk of introducing bacteria into bloodstream
State the Common clinical symptoms of Acute hematogenous osteomyelitis.
Acutely febrile: a sudden onset of a high fever.
Septicemia: is a severe and potentially life-threatening condition that occurs when the body’s response to an infection leads to widespread inflammation and systemic symptoms.
Pain, tenderness at site of infection worsening with movement & wt. bearing.
Diminished function, reduced range of motion
Primarily acute but chronic infections may occur due to failed antimicrobial therapy.
Neonatal osteomyelitis more likely assoc. with septic arthritis of adjacent joint.
Describe the Etiology & the process…. of Acute hematogenous osteomyelitis (AHO)
Acute hematogenous osteomyelitis (AHO) primarily caused by bacteria in bloodstream.
BUT note: Fungi common cause in immunocompromised.
AHO more common in children
Thought that they experience frequent episodes of asymptomatic bacteremia.
In children (prepubertal), metaphyses richly vascularized, as producing new bone at a rapid rate.
Bacteria in bloodstream may seed bones where blood flow is abundant & slow.
Bacterial seeding of richly vascularized metaphyseal region, triggers inflammation
Describe the process of Acute hematogenous osteomyelitis (AHO) in children.
Valveless sinusoidal loops of metaphyseal venules have sluggish flow which facilitates bacterial invasion.
Bacteria seeding within metaphyseal vessels (nutrient artery & vein)
Infection develops inducing an acute inflammatory reaction in metaphysis.
Abscess escapes via Haversian systems & Volkmann canals, into cortex of bone, lifting or rupturing the periosteum (loosely attached in children).
Growing abscess in cortex & extending along periosteum, impairs blood supply, resulting in an area(s) of bone necrosis “sequestrum”.
State the Indicators of “chronic osteomyelitis”
Dead Bone (Sequestrum):
Chronic osteomyelitis often results in the formation of dead bone tissue, known as sequestrum. This necrotic tissue is a consequence of the infection disrupting blood supply to a portion of the bone, leading to bone death. Sequestra can contribute to the chronic nature of the infection and may need to be surgically removed to facilitate healing.
New Bone Formation (Involucrum):
In response to chronic inflammation and infection, the body may attempt to wall off the affected area by forming new bone around the dead or infected region. This new bone is called involucrum and is a part of the body’s defense mechanism to contain the infection. However, it can also contribute to the chronicity of the condition.
Sinus Tracts: Chronic osteomyelitis may give rise to the formation of sinus tracts or channels that connect the infected bone to the skin surface. These tracts can serve as pathways for the drainage of pus or infected material from the affected bone.
Recurrent Infections: Patients with chronic osteomyelitis may experience recurrent episodes of infection, leading to a persistent or relapsing course of the condition. This can occur if the underlying infection is not adequately treated or if there are factors that impede proper healing.
Persistent Symptoms: Chronic osteomyelitis is characterized by persistent symptoms such as pain, swelling, and drainage from the affected area. These symptoms can persist over an extended period, contributing to the chronic nature of the condition.
Prevalence of acute hematogenous osteomyelitis in different bones in children.
AHO mostly occurs often in ___________children & commonly involves the metaphysis of long bones, esp. ____________and _________. Rather than the flat bones or spine
In children, metaphyses grow the fastest, i.e. around the knee, why?
> 50% infections occur in what bones?
AHO mostly occurs often in prepubertal children & commonly involves the metaphysis of long bones, esp. tibia & femur. Rather than the flat bones or spine
In children, metaphyses grow the fastest, i.e. around the knee, as richly vascularized to produce new bone rapidly.
> 50% infections occur in the femur, tibia or fibula
In adults, long bones less well-served by circulatory system rather ____________ receive more blood flow.
Common site of bone infection in adults: ________________
Why does vertebral osteomyelitis often occur in two contiguous vertebrae bodies & the intervertebral disc?
What is osteomyelitis in long bones mostly from in adults?
In adults, long bones less well-served by circulatory system rather vertebrae receive more blood flow.
Common site of bone infection: vertebrae (followed by long bones, pelvis & clavicle)
Primary blood supply of vertebrae is the segmental arteries, which perfuse adjacent vertebrae. So vertebral osteomyelitis often occurs in two contiguous vertebrae bodies & the intervertebral disc
Osteomyelitis in long bones mostly from a contiguous site e.g. secondary to prosthetic implant infection
Various bacteria can cause osteomyelitisresponsible for most bone infections?
Antimicrobial resistance is a challenge for treatment & significant no. of infections caused by which bacterium?
State the less common causes of osteomyelitis. (bacteria)
Various bacteria can cause osteomyelitis BUT S. aureus& coagulase-negative staphylococci i.e. S. epidermidisresponsible for most bone infections.
Antimicrobial resistance is a challenge for treatment & significant no. of infections caused by methicillin-resistantS. aureus(MRSA) strains.
Less common: Streptococcus spp., *Pseudomonas aeruginosa (foot bone infections),Enterobacteriaceae spp.
Define Peri-prosthetic joint infections.
Peri-prosthetic joint infections (PJIs) - infections occurring after joint reconstruction or replacement surgery (arthroplasty).
How many % of patients post-operatively are affected by Peri-prosthetic joint infections BUT assoc. with significant cost & morbidity.
Acute PJIs present within how many weeks of the index surgery?
May result from intraoperative seeding of implants or via hematogenous spread (blood stream infection) during early post-operative period.
Chronic PJIs occur after how long after the index surgery?
May result from a low-virulence organism seeded intraoperatively or failed treatment of earlier acute PJI.
Affect ~1-2% of patients post-operatively BUT assoc. with significant cost & morbidity
Acute PJIs present ≤4wk of the index surgery. May result from intraoperative seeding of implants or via haematogenous spread (blood stream infection) during early post-operative period
Chronic PJIs occur >1mth after the index surgery. May result from a low-virulence organism seeded intraoperatively or failed treatment of earlier acute PJI
Discuss the process and virulence factors involved to successfully cause Peri-prosthetic joint infections.
When a prosthetic device/ implant is placed in the body it’s quickly coated with adhesins from host’s extracellular fluid e.g. fibronectin, fibrin, fibrinogen. Fibronectin is an important adhesin for S. aureus
Once the implant is coated with these proteins it provides a ‘foundation’ for biofilm formation by certain bacteria
Biofilms: “a community of microorganisms in a structural matrix usually adherent to an underlying substratum”
Then produce an extracellular layer largely composed of polysaccharides e.g. polysaccharide intercellular adhesion, Glycerol teichoic acid
Biofilms encapsulate bacteria, preventing antibiotic perfusion thus reducing antimicrobial effectiveness
Describe PJI by process by S. aureus.
Post surgery traumatized bone releases several factors e.g. Mg2+ & prosthesis covered with extracellular matrix proteins
Biofilm comprises bacteria undergoing various metabolisms, embedded in excreted matrix mainly composed of polysaccharides, extracellular DNA & proteins
Antimicrobial action of immune cells hindered by biofilm
Diffusion gradients of nutrients & O2 develop i.e. higher conc. in upper layer vs. accumulation of metabolic wastes at lower level.
S. aureus quorum sensing (communication) helps regulate metabolism activity, production of virulence factors & other bacterial responses.
& (8) bacteria may persist within abscesses in surrounding tissues &/ OR exist within bone osteoblasts &/ OR colonize osteocyte lacuno-canalicular network (OLCN)
(Enabling S. aureus to evade the immune system & cause future reinfections
Outline the Pathogenic mechanisms by S. aureus during bone infection.
- Intracellular infection of osteoblasts, osteoclasts & osteocytes.
-Reservoir of S. aureus for long-term persistence in the bone. - Invasion of osteocyte-lacuno canalicular network (OLCN)
-Allows evasion of host immune cells - Survival in macrophages
-‘Trojan horse’ macrophages enable bacteria dissemination - Biofilm formation on bone &/or implants
-Resistance to antibiotic therapy - Staphylococcal abscess communities:
-S. aureusat the center of abscess surrounded by a fibrous pseudocapsule & layers of dead & live immune cells
Etiology of Peri-prosthetic joint infections.
PJIs are mostly caused by bacteria, notably:
Coagulase-negative staphylococci (30–43%)
S. aureus (12–23%)
Beta hemolytic Streptococcus spp. (9–10%)
Enterococcus spp. (3–7%)
Gram-negative organisms (3–6%) & anaerobes (2–4%)
Unusual organisms that can also cause PJIs incl.:
*Propionibacterium acnes considered non-pathogenic & may be dismissed as a contaminant BUT it’s become a common cause of shoulder PJIs
*Mycobacterium spp., Mycoplasma hominis, Corynebacterium spp., Actinomyces spp.
*Fungi e.g. Aspergillus fumigatus, Histoplasma capsulatum, Sporothrix schenckii, Candida spp
Osteomyelitis: Leading pathogens according to site
Microorganisms ranked from high to low prevalence or epidemiological importance.
State the micro-organisms ranking for the following.
1. Vertebral osteomyelitis
2. Diabetic foot infection
3. post-traumatic infection
4. Prosthetic-joint infection
- Vertebral osteomyelitis
Staphylococcus aureus
Gram-negative aerobic bacilli
Streptococcus species
Mycobacterium tuberculosis - Diabetic foot infection
Staphylococcus aureus
Pseudomonas aeroginosa
Streptococcus species
Enterococcus species
Coagulase-negative Staphylococci
Gram-negative aerobic bacilli
Anaerobes - post-traumatic infection
Staphylococcus aureus
Polymicrobial
Gram-negative aerobic bacilli
Anaerobes - Prosthetic-joint infection
Staphylococcus epidermidis
Staphylococcus aureus
Polymicrobial
Streptococcus species
Gram-negative aerobic bacilli
Propionibacterium acnes (esp. shoulder PJIs)
P. aeruginosa is an important cause of what osteomyelitis?
An important cause of osteomyelitis of tarsal & metatarsal bones of foot, after penetrating trauma e.g. stepping on protruding nail
P. aeruginosa septic arthritis following nail puncture wound to foot is a further complication.
P. aeruginosa also common cause of hematogenous osteomyelitis in intravenous drug users.
