Aetiology
Osteomyelitis may be caused by haematogenous spread of infection, from direct inoculation of micro-organisms into bone, or from a contiguous focus of infection. A trivial skin infection may cause bacteraemia, or it may result from more serious infections such as acute or subacute bacterial endocarditis. Intravenous drug misuse has been linked to haematogenous osteomyelitis involving the long bones or vertebrae.[4][5]
The pattern of bone infection is changing. Worldwide, childhood acute haematogenous osteomyelitis and septic arthritis are common, with chronic disease following inadequate initial management. Paediatric spondylodiscitis (infection involving the intervertebral disc and adjacent vertebrae) is rare and accounts for 1% to 2% of all children with osteomyelitis.[6] Differentiation between discitis and vertebral osteomyelitis may be difficult.[6] Associated pathogens are similar to those in osteomyelitis. Spondylodiscitis is most common in children aged <5 years, whereas vertebral osteomyelitis is more common in older children, in whom Mycobacterium tuberculosis and Salmonella are possible causes.
In the developed world, bone infection in adults is now mostly seen after injury or surgery (contiguous focus osteomyelitis).[2] It is often implant-related. The rising number of patients living longer with multiple comorbidities and the increasing incidence of bone and joint surgery have led to a higher proportion of contiguous focus infections, with haematogenous infections becoming less frequent, except in immunocompromised people.
Common organisms implicated in acute osteomyelitis are Staphylococcus aureus, streptococci, Enterobacteriaceae, and anaerobic bacteria. Native vertebral osteomyelitis is commonly monomicrobial and most frequently due to S aureus.[7]
Different groups of patients are more susceptible to different organisms. Common organisms in acute haematogenous osteomyelitis are listed below by age:
Infants:
S aureus[6]
Group B streptococci[6]
Aerobic gram-negative bacilli (e.g., Escherichia coli)[6]
Candida albicans.
Children 3 months up to 5 years:
S aureus[6]
Kingella kingae (increased incidence in children <4 years)[6][8]
Group A streptococcus[6]
Streptococcus pneumoniae[6]
Haemophilus influenzae (in those not immunised)
Pseudomonas (due to foot puncture wounds).[9]
Children >5 years:
Adults:
S aureus[2]
Coagulase-negative staphylococci[2]
Aerobic gram-negative bacteria[2]
Anaerobic gram-positive Peptostreptococcus species.[2]
Older adults:
Gram-negative bacilli.
Patients with intravascular devices:
S aureus
Candida species.
Patients who misuse intravenous drugs:
S aureus
Pseudomonas aeruginosa.
Patients with sickle cell disease; patients from developing countries:
S aureus
Salmonella species.[6]
Consider Brucella, Burkholderia pseudomallei (melioidosis), and dimorphic fungal infections in endemic areas.
Pathophysiology
Bacteria that enter the bloodstream exist in a free-floating planktonic state. Most osteomyelitis is caused by biofilm-forming bacteria. These bacteria express surface components called adhesins that bind to proteins found in host tissues. Once attached, the bacteria produce a polysaccharide extracellular matrix, forming a biofilm.[10][11][12][13][14] Once sufficient numbers of organisms are present in the biofilm, a complex system of cell-to-cell signalling develops, known as quorum sensing. This controls further development of the mature biofilm. It may also propagate the spread of infection by controlling separation of fragments of this biofilm which seeds to local sites. Some of the organisms in biofilm are able to enter a dormant state with minimal cellular division. In this state, antibiotics that act on cell division are ineffective.[15][16] Similarly the organisms are also partially protected from the host immune system within the glycocalyx. The sensitivity of a culture in the laboratory on an agar plate (in vitro) may bear no relationship to the ability of the same antibiotic to kill bacteria in a biofilm in dead tissue or in an implant (in vivo). In vitro biofilm models may be more representative. Staphylococcus aureus has been shown to express a number of virulence factors, and can invade living cells and survive inside osteoblasts.
Haematogenous osteomyelitis usually involves the metaphysis of long bones in children or the vertebral bodies in adults. In acute haematogenous osteomyelitis, infection spreads through bone via Haversian and Volkmann canal systems. The joint is usually spared, unless pus breaks through the metaphyseal cortex forming a subperiosteal abscess in an intracapsular metaphysis, as is found at the proximal radius, humerus, or femur and ankle. The capillary anatomy in the metaphyseal area contains venous sinusoids which allow the bacteria to stagnate, while the lower pH and oxygen tension near the growth plate facilitate bacterial growth. Septic arthritis of an adjacent joint may be an early complication of acute osteomyelitis in children.[17]
Haematogenous spread to the spine was thought to occur via Batson’s venous plexus, which drains blood from the urinary system, breast, and prostate to the internal vertebral plexus.[18][19] This theory is no longer generally accepted.
Classification
Cierny-Mader classification[1]
Three physiological classes of patients (A, B, C):
A: people with no comorbidities that compromise outcome; able to withstand surgery and antibiotic therapies
B: those with comorbidities that directly reduce the likelihood of wound healing, reduce the efficacy of drug treatment, or increase the risks of surgery
C: people who are so severely compromised that treatment has an unacceptable risk-benefit ratio, and therefore the treatment of their infection can be more harmful than the condition.
Four anatomical types (I to IV) based on the degree of bone involvement:
I: medullary and endosteal bone; mostly associated with haematogenous infection
II: superficial osteomyelitis from contiguous focus infection; often arises in the base of a varicose ulcer, or from external trauma or a pressure sore
III: both medullary and cortical involvement; the osteomyelitis is limited to part of the circumference of the bone, leaving a healthy portion of the bone to maintain stability
IV: diffuse involvement of the entire circumference of the bone.
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