Bone and Joint Infections

Mequanent kassa (B Pharm, MSc)

Department of Clinical pharmacy, University of Gondar
Introduction
 Bone and joint infections are comprised of two disease
processes known, as
osteomyelitis and
septic or infectious arthritis.
EPIDEMIOLOGY
 Acute osteomyelitis has an estimated annual incidence
of 0.4 per 1,000 children.
 In adults, osteomyelitis caused by contiguous spread,
including
- postoperative,
- direct puncture, and
- associated with adjacent soft tissue infections,
comprises 47% of infections.
EPIDEMIOLOGY Continued…
 Infectious or septic arthritis is an inflammatory reaction
within the joint space.
 Distinct from osteomyelitis, septic arthritis is one of the
most common causes of new cases of arthritis.
 The incidence of proven or likely septic arthritis is 4 to 10
cases per 100,000 patient-years per year.
 The incidence of septic arthritis increases to 70 cases per
100,000 patient-years among patients that have rheumatoid
arthritis
ETIOLOGY
Osteomyelitis
 Classification is based on the mode of acquisition of the bone
infection.
- through the bloodstream
- through contiguous osteomyelitis.
- inoculation osteomyelitis such as
- from trauma, puncture wounds, or surgery
 classifiction can also based on the duration of the disease.
- Acute osteomyelitis... days to 1 week
- chronic infections…. More than 1 month before therapy
 Hematogenous osteomyelitis involves one bone whereas
contiguous osteomyelitis can present in multiple bones
ETIOLOGY
Septic Arthritis
 can result by
- spread from an adjacent bone infection,
- direct contamination of the joint space, or
- hematogenous dissemination.
 hematogenous spread of the disease comprises the
majority of infections
 one-third of people with septic arthritis are children
younger than 2 years of age.
PATHOPHYSIOLOGY
Hematogenous osteomyelitis is typically a disease of
the growing bone in children and most cases occur in
patients younger than 16 years of age.
Types of Osteomyelitis, Age Distribution, Common Sites, and Risk Factors
PATHOPHYSIOLOGY hematogenous
osteomyelitis continued…
 Unique features of the anatomy and physiology of long bones appear to
predispose them to become infected.
 There is slowing of blood flow passing through the hairpin capillary
loops ( a structure found in arterioles).
 This sludging of blood flow allows bacteria present within the
bloodstream to settle and initiate an inflammatory response.
 In addition to these structural features, there also appears to be less
active phagocytosis of the bacteria.
 After the bacteria settle in the bone, avascular necrosis can occur from
occlusion of the nutrient vessels and release of bacterial enzymes.
 In addition there is some evidence that trauma is associated with
developing an infection in specific bones.
 Once the infection is initiated, exudate begins to form within the bone
marrow and the fluid accumulates under increased pressure.
continued…
 In children, hematogenous osteomyelitis typically involves
a single bone and has a predilection for involvement of the
long bones, such as
- the femur, tibia, humerus, and fibula
 In contrast, neonatal infections commonly involve multiple
bones.
 Vertebral infections are common in patients older than 50
years of age.
 Chronic osteomyelitis is more likely to occur if large
segments of bone become avascular and necrotic.
bacteriology of hematogenous osteomyelitis
 Responsible pathogen for hematogenous osteomyelitis,
- staphylococcus aureus, is responsible for more than
80%
- with group A Streptococci and Streptococcus
pneumoniae accounting for a few cases.
- Kingella kingae, emerging as a pathogen in children less
than 3 years of age.
 Vertebral osteomyelitis pathogen
- Staphylococci cause approximately 60%
- gram-negativeparticularly E. coli
 .
Continued…
 Osteomyelitis in the IV drug user has unique features.
More than 50% of infections involve the vertebral
column
20% of infections in the pelvic girdle or sternoarticular
much less frequent within the extremities.
gram-negative organisms being responsible for 88% of
infections.
- Pseudomonas aeruginosa, 78% of all infections.
- Klebsiella, Enterobacter, and Serratia species
found but less commonly
Continued…
 sickle cell anemia related Osteomyelitis pathogen
- Two thirds of bone infections caused by Salmonella
species
- The rest caused by staphylococci and other gram-
negative organisms.
Direct Inoculation Osteomyelitis
 caused by direct entrance of organisms from a source
outside the body.
-Penetrating wounds (e.g., trauma),
- open fractures, and
- various invasive orthopedic procedures
 puncture injuries to the feet are associated with gram-
negative
 bone and cartilage infections caused by P.aeruginosa,
S. aureus
Contiguous-Spread Osteomyelitis
 It is caused by secondary to spread from an adjacent soft
tissue infection.
- most often involves the distal extremities.
- Less infections can spread from infected teeth.
 occurs most commonly in patients older than age 50
because of predisposing factors:
- hip fractures or vascular disease
 Responsible pathogens includes:
- S. aureus most common organism causing infections
with
- gram-negative bacilli, occur frequently.
- P. aeruginosa, streptococcus,
- E. coli, Staphylococcus epidermidis, and anaerobes
Contiguous Osteomyelitis Continued…
 Osteomyelitis in association with severe vascular
insufficiency are extremely difficult to manage. B/s most of
these patients have diabetes mellitus or severe
atherosclerosis, and they develop their infections by
contiguous spread.
 patients with vascular disease develop osteomyelitis in their
toes and fingers, and there is usually an adjacent area of
infection, such ascellulitis or dermal ulcers.
 Infections in these patients are polymicrobial include
- staphylococcus and streptococcus or combination of
staphylococcus,streptococcus, and Enterobacteriaceae.
- Enterococci and anaerobic organisms also can be involved.
Contiguous Osteomyelitis Continued…
 Predisposing factors in patients who have anaerobic
osteomyelitis include
- vascular disease
- bites
- contiguous infections
- peripheral neuropathy
- hematogenous spread, and trauma.
 The anaerobic infections in association with diabetes
mellitus almost always occur within the feet.
 Bacteroides fragilis and Bacteroides melaninogenicus
comprise the majority of anaerobic isolates
Septic Arthritis
It usually is acquired by hematogenous spread.
The synovial tissue is highly vascular and does not
have a basement membrane, so organisms in the blood
can easily reach the synovial fluid.
Characteristics of Acute Septic Arthritis
Organisms can gain access to the joint

deep-penetrating wound injury

Intra articular steroid injections
arthroscopy
prosthetic joint surgery, and spread to the joint from a
contiguous focus of osteomyelitis.
Trauma
Continued…
 Predisposing factors for septic arthritis in adults.
Diabetes mellitus
Immunosuppressive states
Preexisting arthritis.
IV drug abusers
Endocarditis
Preexisting abnormal joint architecture, joint trauma,
and surgery
Rheumatoid arthritis
Pathogens cause septic arteritis
 S.aureus, the single most common infecting organism
is found in 37% to 65% of cases of nongonococcal
bacterial arthritis.
 Streptococcal infections are the second most common
and
 Gramnegative Organisms Are Less common.
- E. coli is the most common
 P.aeruginosa is the most frequent organism in IV drug
abusers.
Neonates Pathogens
 the most frequent organism found in Neonates
- S. aureus
- group B Streptococcus, and
- gram-negative organisms.
 the most common pathogens in children younger than 5 years
of age.
- S. aureus and streptococcus
- H. Influenza, which the most common pathogen in these
children, can be eliminated by immunization with the conjugate
Hib vaccine.
- If a child has not been fully vaccinated or is
immunocompromised, Hib may be a cause.
Adult Pathogens
 S. aureus is responsible for the vast majority of
nongonococcal infections.
 Gonococcal arthritis is a common manifestation of
disseminated gonococcal infection occurring in 42% to
85%.
 Septic arthritis can be caused by fungi,viruses such as
varicella-zoster, rubella, or parvovirus.
 Septic arthritis is rarely caused by
- Salmonella, Corynebacteria, Brucella,
- Neisseria meningitides, Mycoplasma niae, or
Ureaplasma urealyticum.
Clinical Presentation of Hematogenous
Osteomyelitis
Radiologic and Laboratory Tests of Osteomyelitis
 Radiographs of the involved area should be obtained to rule out other
processes such as a fracture.
 Bone changes characteristic of osteomyelitis appear late and are not
typically seen until at least 10 to 14 days after the onset of the infection.
 laboratory abnormalities seen.
- erythrocyte sedimentation rate (ESR),
- C-reactive protein, and
- WBC count
 The degree of abnormality of these laboratory findings does not correlate
with the disease outcome; however, they are useful for monitoring therapy.
 C-reactive protein can be elevated because of the presence of
inflammation, and it can be substituted for the ESR. C-reactive protein is
generally the more sensitive marker of response to therapy and often
increases and decreases before the ESR.
Radiologic and Laboratory Tests in septic
arthritis
 The presence of purulent fluid usually indicates the presence of
a septic joint septic arthritis.
 The synovial fluid WBC count is usually 50 to 200 ×
103/mm3(50 × 109to 200 × 109/L) when an infection is present.
 Serum WBC, ESR, and C-reactive protein may not be useful
acutely in septic arthritis.
 Half the patients with an infected joint have a low synovial
glucose level, usually less than 40 mg/dL (2.2 mmol/L).
 Radiographs of infected joints often reveal distension of the
joint capsule with soft tissue swelling in the adjacent space.
 Magnetic resonance imaging can be helpful in identifying an
infected joint, especially the hip.
General Approach to Treatment

Osteomyelitis
 It is important to stress that early antibiotic therapy can alleviate:
- The need for surgery
- Subsequent sepsis
- Chronic infection
- Disruption of longitudinal bone growth
- Angular deformity of the bone.
 A delay in treatment can allow bone necrosis to occur and make
eradication of the infection much more difficult.
 In these patients with chronic osteomyelitis, exacerbations of the infection
can result if all necrotic tissue is not removed surgically and all
microorganisms eliminated.
 If a patient with hematogenous osteomyelitis does not respond after the
initiation of adequate antibiotic therapy
- The patient should undergo surgical debridement of the infected area.
Continued…
 Septic arthritis
 Patients with septic arthritis are typically admitted to
the hospital to obtain synovial fluid and blood cultures
and initiate antimicrobial therapy.
 It is important to stress early initiation of antibiotic
therapy to avoid complications includes:
- vascular necrosis
- limb-length discrepancy, and
- pathologic fractures
Pharmacologic Therapy
Empiric Treatment of Osteomyelitis
Continued…
 With staphylococcus being the most common bacteria in
osteomyelitis, resistance patterns must be considered when deciding
on an empiric agent.
 low evidence of resistant strains of S. aureus, nafcillin is the drug of
choice.
 cefazolin or cephalexin are often chosen to treat susceptible strains due
to ease of dosing compared to nafcillin.
 Clindamycin can be used in less severe cases.
 If 10% or more of the surrounding community S. aureus isolates are
methicillin resistant, then an agent active against MRSA should be
selected. Vancomycin is the drug of choice in this case.
 If the patient is severely ill, then both vancomycin and nafcillin should
be used for empiric treatment.
 If patients are allergic to penicillins or cephalosporins or are infected
with MRSA, vancomycin, clindamycin, or linezolid can be used.
Antimicrobial Agents for the Treatment of Osteomyelitis
Treatment of Osteomyelitis continued..
Continued…
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Oral Antibiotic Therapy
 Criteria for the use of oral outpatient antibiotic therapy for
osteomyelitis include all of the following:
A. Confirmed osteomyelitis
B. Initial clinical response to parenteral antibiotics
C. Suitable oral agent available
D. Compliance ensured
 Suitable candidates for oral route are children with good
clinical response to intravenous therapy and adults without
diabetes mellitus or peripheral vascular disease
Continued…
 Two primary populations that have benefited from oral treatment.
 Children responding to initial parenteral therapy may receive oral
therapy:
- dicloxacillin, cephalexin,
-clindamycin, or amoxicillin depending on their culture and
susceptibility results.
 Adults with an infecting organism susceptible to a fluoroquinolone.
without diabetes mellitus or peripheral vascular disease.
 The use of oral antibiotics is well studied in children.
 Typically, injectable antibiotics are used initially and then switched
to oral antibiotics when:
- there was a decrease in the signs of inflammation
- decrease the ESR or when the patient was afebrile for 3 days.
Continued…
 The patients underwent surgical drainage.
- If pus was obtained on the initial needle aspirate, or
- if a reduction in fever, local swelling, and
tenderness did not occur despite adequate
rest,immobilization, and intensive antibiotic therapy.
if oral therapy is inappropriate or not strictly adhered
to patients may developing chronic osteomyelitis
Duration of Antibiotic Therapy
 The specific duration of antibiotic therapy needed in the management of
osteomyelitis is usually 4 to 6 weeks.
 For children with hematogeous osteomyelitis a 20 days of antibiotic therapy
is recommended:
- after initial parenteral therapy as long
- the C-reactive protein level normalized within 7 to 10 days.
Important parameters to assess therapy
 Improvement in the patient’s clinical signs and symptoms
 Normalization of the C-reactive protein level or ESR
 If signs or symptoms are still present at 6 weeks, therapy should be
extended.
 Duration of antibiotic administration for vertebral osteomyelitis may vary
depending on the infecting organism.
 The IDSA guidelines recommend a minimum of 6 weeks of parenteral
therapy or highly bioavailable oral therapy.
Osteomyelitis in Special Populations

 Osteomyelitis in patients with sickle cell hemoglobinopathies is caused

by either
- Salmonella or S. aureus .
 Thus, empirical antibiotics of first choice
- ceftriaxone or cefotaxime.
- Alternatives are chloramphenicol and ciprofloxacin (in adults).
 Osteomyelitis in patients with IV drug abuse require coverage for gram-
negative, empirical treatment include:
- ceftazidime or cefepime 2 g IV every 8 hours.
- If compliance can be ensured, oral ciprofloxacin 750 mg twice daily.
- Antibiotic therapy in these patients should be continued for at least 4
to 6 weeks.
Continued…
After surgery or from contiguous spread of an adjacent
soft tissue infection. S. aureus is the single most
common organism.To provide the required broad-
spectrum coverage,
- Nafcillin 2 g IV every 4 hours plus ceftazidime or
cefepime 2 g IV every 8 hours.
Special population Continued
 Patients with established vascular insufficiency develops
osteomyelitis benefted from.
 penicillinase-resistant penicillin incombination with ceftazidime is
the preferred initial therapy.
 If anaerobes are suspected, an antianaerobic
cephalosporin (e.g., cefoxitin) or clindamycin plus ceftazidime can
be substituted.
 Ampicillin may need to be added to the regimen to provide
coverage against enterococci.
 low cure rates are there in this type of patients, Despite aggressive
antibiotic therapy along with surgical debridement, therefore,
Amputation of the involved area may be required to obtain a cure of
the infection
Septic Arthritis
 The three most important therapeutic maneuvers in the management of
infectious arthritis are
-appropriate antibiotics,
- joint drainage, and joint rest.
 In neonates, the infecting organisms vary widely, and empirical therapy thus
must provide broad-spectrum coverage.
- nafcillin or oxacillin plus a third-generation cephalosporin is appropriate.
 Children younger than 5 years of age who have been immunized for Hib
should receive nafcillin, oxacillin, or cefazolin.
 In children older than 5 years of age and in adults, initial therapy with a
penicillinase-resistant penicillin or first-generation cephalosporin is
appropriate to provide the necessary coverage against S. aureus.
 Shorter durations of antimicrobial therapy are needed to treat infectious
arthritis compared to osteomyelitis.
- 2 to 3 weeks of antibiotic therapy is adequate.
Home Antibiotic Therapy
 Administration of antibiotics in the home environment and
the use of antibiotics with extended elimination half-lives
are commonly used.
 Patients screened to home antibiotic therapy include:
- Those who are receiving a stable treatment program
- Those who are interested and are motivated in
participating.
- Those who have good venous access
- Those who have support from family members or
neighbors
- Those have home facilities for storage and refrigeration.
EVALUATION OF THERAPEUTIC OUTCOMES
Monitoring protocol
THE END