Ch 47 Osteomyelitis and implant-infections Flashcards
Osteomyelitis
- inflammatory condition of bone, is usually considered to be caused by an infectious agent (bacteria, fungi, or viruses)
- Under normal physiologic conditions, bone is resistant to colonization and subsequent infection
- an inciting event must occur to lead to the development of osteomyelitis > Trauma, the implantation of foreign material (implants), inoculation with infectious organisms, and/or an immunocompromised patient
- osteomyelitis > classified as hematogenous or posttraumatic
Waldvogel staging system
based on the cause of the infection (hematogenous spread vs. direct inoculation or contiguous spread from soft tissues)
- acute osteomyelitis = infections that occur within days to weeks of the inciting event
- chronic = develop over months or years with key characteristics of low-grade inflammation, persistence of microorganisms, and the presence of sequestrum and fistulous tracts.40
treatment success influenced by three central factors
(1) viability and stability of the bone
(2) virulence and antimicrobial susceptibility of the organism
(3) condition of the soft tissue envelope
variables that can determine whether or not an infection develops (3)
The presence of virulence characteristics (i.e., different adhesins, production of toxins)
antimicrobial susceptibility patterns
propensity to form a biofilm
most common bacteria
Staphylococcus spp. (approximately 60% cases)
E.coli
Streptococcus
Polymicrobial infections > one retrospective study identifying mixed populations in 42% of cases
Staphylococcus intermedius as most common, whereas recent reports suggest S. pseudintermedius is more common
other bacteria
- in some cases methicillin-resistant strains represent close to 50% of the bacteria being isolated > reflects the outcomes of phylogenetic reclassification
- Gram-negative: Pasteurella, Pseudomonas, Proteus and Klebsiella
- Gram-positive: Corynebacterium spp, enterococci
- Anaerobic: Bacteroides, Nocardia, Clostridium, Actinomyces, Fusobacterium isolated from 64% of cases in one retrospective study
- Fungal:Blastomyces, Aspergillus, Candida, Coccidioides
Pathogenesis
- Posttraumatic/direct inoculation is thought to be the most common in dogs and cats.
- Hematogenous occur most frequently in young animals.
- Rarely, osteomyelitis the result of direct spread from an adjacent soft tissue infection.
Describe the pathogenesis of osteomyelitis
- Cytokines and growth factors are found in altered local concentrations during infection
- Normal osteoclast and osteoblast activity is influenced by cytokines/GF > Contribute to necrosis and resorption of the bone
- Leads to ischaemia due to collapse of vascular channels (Haversian, volksman and canaliculi)
- Segments of bone lacking an adequate blood supply have a propensity to form sequestra and offer a protected environment for bacterial organisms > presence of bone ischemia alone is enough
- At the edge of the ischemic bone is a reactive hyperaemia > increase in osteoclastic resorption > development of osteoporosis
How is the degree of periosteitis correlated with the aggressiveness of the infection
- osteoblastic production of new bone occurs secondary to periosteal irritation: The degree of periostitis correlated to the aggressiveness of the infection.
- less aggressive > slowly separates the periosteum from the bone, resulting in thickening of the cortex
- more aggressive > lamellar changes where layers of bone are laid down adjacent to one another
Posttraumatic Osteomyelitis
when microbial organisms are inoculated into areas adjacent to bone: penetrating wounds (FB, bite wound), spread from local soft tissue, or from surgical wounds i.e. implant
- bacterial-host interactions are complex and multifactorial, many variables if infection
- Host defense mechanisms (competent immune response) are critical in the prevention
>not every colonized implant result in infection
Competent host defence can be hampered by tissue trauma, (surgical or trauma) > vascular compromise and tissue ischemia
- tissue trauma is central in the development of posttraumatic osteomyelitis
- Data from human > tissue trauma may occur at the cellular level.
- Study:
inflammatory cells (neutrophils) collected from intraop lavage fluid. Analysis demonstrated that although activated, they were unable to clear the bacteria, presumably because of biofilm formation.
During activation and attempted phagocytosis of the bacteria within the biofilm, neutrophils release cytotoxic and proteolytic substances > contribute to tissue injury and osteolysis
osetomyelitis: patient and bacterial factors?
- patient factors:
presence of sepsis
systemic trauma
major organ dysfunction - bacterial characteristics:
virulence (i.e., different adhesins, production of toxins)
antimicrobial sensitivity patterns
biofilm
Dogs with pre-op TPLO nasal/rectal swabs which isolated methicillin resistant sS.Pseud were….
13-14 times more likely to develop a SSI cause by the rganism within 30 days
Implant-Associated Infections
- many have a nosocomial origin with some degree of antimicrobial resistance
- attributable to the presence of biofilms > more resistant to antimicrobial therapy compared to their free-floating, or planktonic, counterparts
- Implant-associated infections and osteomyelitis classified as deep or organ/space surgical site infection
- The presence of an implant +/- procedure performed for implant application can result in the development of osteomyelitis.
- trauma can lead to bone necrosis > predispose to bacterial colonization and biofilm formation within the necrotic bone.
most common sx site infection
- Recent studies document S. pseudintermedius as the predominant isolate associated with surgical site infections in dogs
- methicillin-resistant strains represent close to 50%
- nosocomial origin is supported by Nazarali et al
presence of implant
- implant is present > conditioning layer of proteins and polysaccharide molecules adsorbed to the implant surface develops
- bacterial adhesion can occur via fibronectin within the conditioning film and bacterial adhesins
- Successful treatment of an implant-associated infection is influenced by the presence or absence of a biofilm
bioflim
concept > was proposed by Costerton 1978
- a microbially derived sessile community
- cells are irreversibly attached
- are embedded in a matrix they have produced called glycocalyx, a slimy exopolysaccharide material.
- exhibit an altered phenotype: growth rate and gene transcription
The development dependent on bacterial, substrate, and host factors
- initiated by the reversible adherence of planktonic organisms
- complex molecular pathways and genetic regulation are responsible for biofilm formation.
» importance of quorum sensing, the ability of bacteria to coordinate gene expression based on population density by monitoring the concentration of autoinducers
- also important in the production of virulence factors (e.g., exotoxins).
- S. aureus interactions with receptors of innate immunity alter the bone remodelling activities of osteoblasts and osteoclasts
quorum sensing,
the ability of bacteria to coordinate gene expression based on population density by monitoring the concentration of autoinducers
five main phases involved in the biofilm formation
reversible attachment,
irreversible attachment,
EPS production,
maturation of biofilm
dispersal/detachment
Biofilm documented advantages
tolerance to antibiotic therapy, and resistance to host defences, contribute to the high rate of treatment failure in osteomyelitis
- extracellular matrix > capture and concentrate nutrients required to survive.
- Growth within the matrix provides protection from:
shear stresses
host phagocytic activities
host protease and oxygen radical defenses - Resistance to antimicrobial therapy >genotypic and phenotypic alterations cause quiescent growth pattern.
- resistance is mediated through:
low metabolic levels
radically downregulated rates of cell division - antimicrobial agents rely on bacterial growth > efficacy is diminished
- extracellular matrix itself acts as a diffusion barrier to slow down the infiltration of some antimicrobial agents, leading to an increase in minimum inhibitory concentration (MIC) of up to 100-fold in most cases
- changes to the microenvironment caues changes in hydration level, hypoxia, and lower pH
- protects bacteria from host defences (phagocytosis, reduce proinflammatory immune responses)
Hematogenous Osteomyelitis
- generally caused by a single bacterial species introduced via the bloodstream and localized to a distant site
- predominantly affecting young, whereby direct seeding of bone occurs during an episode of bacteremia.
- exact mechanism of hematogenous osteomyelitis is not clear, there are a number of theories.
- commonly affects the metaphyseal regions of long bones
- Unopposed infection in the metaphyseal region can spread However, transphyseal vessels are lacking at birth in dogs and cats, thus restricting the infection to the metaphyseal side of the physeal plate
proposed mechanisms (4)
for haematogenous osteo
- attributed to the anatomy > capillaries are characterized by an incomplete basement membrane > mechanism for bacterial translocation during bacteraemia, allowing the bacteria to localize in an area that is relatively inaccessible to the host inflammatory cells
- sluggish blood flow within the metaphyseal capillaries allows bacteria to settle and initiate colonization (not supported by any published data.)
- Alterations in the host immune response have also been implicated.
Experimental studies in mice > Staphylococcus aureus infection may alter the immune response via downregulation of T-cell immunity and immunocytokine production, thus increasing the severity of local osseous destruction - Minor trauma likely plays a role> In experimental studies involving model in rabbits> hematoma, resulting in vascular obstruction and bone necrosis, which creates an ideal site for bacterial colonization
post-truamatic: CS
- acute
Erythema, swelling, localized pain
A fever
systemic WBC elevated,
animal is systemically ill
Signs within a few days of the traumatic event and are often difficult to differentiate from a soft tissue/wound infection - Chronic
most have no systemic clinical signs, history of surgery/implant or other traumatic event.
new or worsening lameness
draining tracts are noted
post-truamatic: Dx rads
Radiographic evaluation
-variable.
- sensitivity 62.5% and specificity 57%
- Initial > soft tissue swelling
- cortical resorption, periosteal proliferation, and loss of trabecular markings.
- lucency around surgical implants
- involucrum = area of live, encasing bone that surrounds dead bone (sequestrum) within a compromised soft tissue envelope
- A nonviable piece of bone that has lost its blood supply is called a sequestrum (can be sterile or infected)
- draining tract develops from the radiolucent area of necrosis that surrounds the sequestrum and extends to the skin surface.
describe this
- A sharply marginated sclerotic piece of bone (sequestrum) surrounded by a radiolucent zone that separates it from the parent bone, both of which are surrounded by sclerotic bone (involucrum).
post-truamatic: Dx u/s
Ultrasonography
- detecting radiolucent foreign bodies (e.g., plant material) in soft tissues adjacent to an area of osteomyelitis
- detecting abscess formation
- evaluation of draining tracts that may be associated with a surgical implant.
post-truamatic: Dx CT/MRI
- (CT) and (MRI)
- useful in identifying sequestra and foreign material
- limited use in the presence of a metallic implant.
- positron emission tomography (PET), and nuclear scintigraphy (technetium-99m)
- intravenous administration of ultrasmall superparamagnetic iron oxide nanoparticles during MRI has shown potential for early detection of vertebral osteomyelitis.
post-truamatic: Dx C&S
- gold standard = positive microbial culture
- collected with care (representative and handled appropriately)
- percutaneous aspirates may deliver positive results, interpret with caution because contamination by surface bacteria
- Image-guided collection of samples is advised (needle biopsy)
- cytologic evaluation and Gram stain should be performed
- Aerobic and anaerobic of swabs
- during surgical (necrotic tissue or implant)
- Improvement in sensitivity implants > sonicated
Antimicrobial therapy
- Bacteriostatic antibiotics should be avoided
- broad recommendations are difficult because of antimicrobial resistance.
- knowledge of local susceptibility patterns is useful
- guided by results of antimicrobial susceptibility testing and response to treatment
- Multiple antimicrobial agents may be necessary
- There is not a general consensus in either human or veterinary medicine on the duration and method of administration of treatment. Large, high-quality clinical trials are scarce
problems:
- inability to achieve sufficient antimicrobial concentrations in affected tissues i.e. some antimicrobials will distribute to the bone only to bind to calcium or other cations (e.g., tetracyclines and potentially fluoroquinolones). -
- Drug penetration and distribution dependent on the molecular weight, lipid solubility, and protein binding of the drug.
- Systemic administration of antibiotic in high doses and for prolonged periods can lead to toxic effects.
Clindamycin is not recommended as a first-choice drug because its use may induce antibacterial-resistant staphylococci.
TMS > keratoconjunctivitis sicca, arthropathy, and other idiosyncratic effects
metal implant coatings
hydrophobic materials
antibiotics,
nitric oxide releasing compounds
silver
have been assessed in both in vitro and in vivo
hydrophobic material polycation N,N- dodecyl,methylpolyethylenimines (PEI) was shown to prevent implant colonization in a sheep osteomyelitis model
theoretical risk of inducing resistant bacterial strains if the antibiotic release profile shows prolonged periods of sub-MIC antibiotic concentrations (Experimental studies in rats have demonstrated efficacy of a gentamicin-coated)
A method of covalently linking antibiotics to a titanium implant surfacehas been developed
In vitro studies evaluating silver nanoparticle coat- ings have shown promise, > yet to be fully assessed in appropriate in vivo or clinical trials
RCT trial
silver-coated ESF pins compared with standard stainless steel pins in 24 human patients identified a 10% reduction in positive culture rates.
Pages 2022 Long-term outcome of tibial plateau leveling osteotomy using an antimicrobial silver-based coated plate in dogs PLOS one
Infected Joint Prostheses
tx goals: eradicate infection, alleviate pain, restore joint function
limited information in the veterinary literature regarding the most appropriate treatment
- Implant infection = catastrophic complication
- prevalence of infection for cementless THR 0 to 3·7%
- Traditionally, removal advised with preservation of surrounding bone stock.
cases series ( 3 dogs)
- described successful revision of infected cemented total hip prostheses with a one-stage removal and replacement with cementless components (Torres 2009)
case report
- describes the diagnosis and treatment of THR infection with surgical debridement, appropriate antibiotic therapy and prosthesis retention (Dan 2014)
In many cases, implant removal is required > excision arthroplasty, arthrodesis, or amputation.
human
- two-stage revision considered to be the gold standard (meta-analysis 2011)
- consists of implant removal followed by treatment of the infection until complete resolution.
- infection is resolved, reimplantation of a prosthesis
- Although numerous reports from the human literature describe successful implant retention and/or one-stage revisions, there is growing concern for increasing antimicrobial resistance given the frequent use of vancomycin
Perioperatvie antibiotics
- An important preventive measure for decreasing the risk for surgical site infection is the use of perioperative antimicrobial prophylaxis
1) base antimicrobial selection on pathogens expected
(2) ensure appropriate timing > peak serum drug concentration at time of first incision
(3) discontinue within 24 hours postoperatively - objective criteria are currently lacking in veterinary medicine
- recommended for contaminated and dirty procedures, some clean-contaminated procedures, procedures involving an implant, and clean procedures lasting longer than 90 minutes
- time-dependent antimicrobials (e.g., penicillins, cephalosporins) administered so that therapeutic levels are present at the time of first incision
- Redosing every two half-lives of the drug is indicated for time-dependent antimicrobials (cephazolin ½ life 47min)
Tx wound infections
One antibiotic attacks the metabolically active organisms
near the surface, while the other targets the sessile organisms. Another strategy
is to apply topical antibiotics, where a much higher concentration of drug is
delivered to overcome the biofilm MIC with low to no systemic absorption and less
risk of resistance. Such drugs as rifampicin, daptomycin, or colistin can easily penetrate
the biofilm matrix, but resistance often rapidly develops. Following with a second antibiotic,
however, clears the biofilm.
Biofilm-based
wound care uses frequent, aggressive debridement to break up the biofilm and
temporarily make the bacteria more susceptible to systemic antimicrobials, combined
with an individualized topical treatment
Commercially available antibiofilm agents include lactoferrin, xylitol, and LipoGel
