Robert Harrington, M.D.
July, 2009
BONE AND JOINT INFECTIONS
Pathogenesis
1. Bone is normally resistant to infection but large inocula of bacteria, trauma or the
presence of foreign bodies may overwhelm host defenses and lead to infection. The
inflammatory response to infection raises intraosseous pressure leading to impaired blood
flow and ischemic necrosis.
2. Thus, in acute osteomyelitis the histology reveals bacteria, pus and thrombosed blood
vessels while necrotic bone sequestra are characteristic of chronic osteomyelitis.
Clinical Presentation
Hematogenous osteomyelitis (acute > chronic):
1. Children: infection due to hematogenous spread is the most common form of
osteomyelitis. Infection is usually located in the metaphyseal area of long bones.
Patients present with fever, irritability and local swelling and tenderness. Symptoms have
usually been present for < 2 to 3 weeks. A history of recent trauma to the affected area is
often elicited.
2. Adults: hematogenous osteomyelitis in adults often involves the vertebral bodies due
their rich, sluggish blood supply. Infection starts in one vertebral body and spreads to the
adjacent disc and vertebral body via the extensive collateral vasculature. Men are
affected twice as often as women and disease is more common after the age of 50.
Bacteremia from any source (recent UTI, cellulitis, catheter infection, endocarditis) can
set up the infection. Patients present with persistent, dull back pain (often worse at night)
and localized tenderness. Systemic symptoms (fever, chills, weight loss) are mild. Long
bones are less often affected since their blood supply diminishes with age.
Contiguous focus (chronic and acute):
1. Predisposing conditions include recent open fracture, recent surgery, or chronic soft
tissue infection (decubitus and/or diabetic ulcers).
2. Most bone infections associated with prostheses or other foreign bodies are the result
of direct inoculation at the time of surgery and can be divided into acute (< 12 weeks) or
chronic (3 - 24 months) infections. Those that occur late after surgery (> 24 months) are
more likely to have become infected from a subsequent episode of bacteremia.
3. Patients with diabetes often have vascular compromise but it is the distal sensory
neuropathy associated with diabetes that is key to the development of neuropathic ulcers
and osteomyelitis. Diabetic foot ulcers greater than 2 cm in diameter are almost always
associated with osteomyelitis.
4. Signs and symptoms of contiguous osteomyelitis include local pain, swelling, edema
and draining sinuses. Fever, systemic symptoms and leucocytosis may be present
depending on the acuity and extent of the infection. The ESR is usually elevated.
Diabetic patients (and others with sensory neuropathies) will not complain of pain.
5. Chronic osteomyelitis implies the presence of a well-established infection that has lead
to the development of bony sequestra often with persistent drainage through sinus tracts.
Patients complain of chronic pain and local drainage but a paucity of systemic symptoms.
The ESR is often > 100. Complications of chronic osteomyelitis include pathologic
fractures, sinus tract epithelial cell cancers and secondary amyloidosis.
Cierny-Mader staging
An alternative classification scheme based on the anatomy of the infection and the
immune status of the host:
Anatomic stage
Stage 1 – medullary infection only, usually due to hematogenous spread or spread
through an intramedullary prosthesis
Stage 2 – superficial infection, always due to a contiguous soft tissue infection, could
also be termed osteotis
Stage 3 – localized infection, full thickness infection (one cortex), but one that can be
resected without compromising the stability of the bone
Stage 4 – diffuse infection (both cortexes) that destabilizes the bone or resection of
which would destabilize the bone
Host status
A – normal host
B – local or systemic condition that compromises healing
C – treatment would be worse than the disease
Microbiology
S. aureus predominates in all types of osteomyelitis.
Coagulase negative staphylococci - foreign bodies.
Streptococci – neonates (group B streptococci), the eldery (enterococci), bites, diabetic
foot osteomyelitis (enterococci).
Gram negative rods – IVDU (P. aeruginosa, S. marcescens), nosocomial, diabetic foot
osteomyelitis (E. coli, P. aeruginosa, P. mirabilis), open fracture, decubitus ulcers (E.
coli).
Anaerobes - diabetic foot osteomyelitis, decubitus ulcers, bites.
Bartonella – HIV.
Brucella - exposed populations.
Fungi (Candida > dimorphic fungi > molds) - immunocompromised, catheter assoc,
IVDU.
Tuberculosis - exposed populations.
Diagnosis
1. Exam, elevated ESR, elevated WBC (acute osteomyelitis).
2. Blood cultures are positive in 50% of cases of acute osteomyelitis
3. Diabetic foot ulcers: probing to bone at the bedside with blunt stainless steel eye probe
detected osteomyelitis in 33 (66%) of 50 ulcers. PPV 89%, NPP only 56%.
1. Imaging
Plain films
a. Need 30 to 50% mineral loss for x-ray changes to be evident - takes at least 14 days
b. Sensitivity 43-75%, specificity 75-83%
c. Plain films are insensitive with acute osteomyelitis
d. Finding in chronic infection - sclerosis, periosteal elevation and sequestra.
CT
a. Best method for detecting small areas of necrosis, gas, foreign bodies.
b. Metallic foreign bodies compromise the image.
MRI
a. Sensitivity 82-100%,
b. Specificity only 53-94% (tumors, fractures, post surgery, sympathetic edema, infarction
– all can look the same – light up on T2 weighted image)
c. Combine with Nu med scans to increase specificity.
d. Not helpful in assessing response to treatment since marrow edema persists for months
after microbiological cure
Bone scan (TC-99 labeled phosphorus)
a. Soft tissue infection will be positive in the immediate (blood flow) and15 minute
(blood pool) phases while osteomyelitis will be positive in these 2 plus the delayed (> 4
hour) images.
b. Sensitivity 69-100% (> 95% in acute osteomyelitis), specificity 38-82% (tumors,
fractures, post-surgery, septic arthritis, Paget’s disease)
WBC scan (Ind-111)
a. Will be positive prior to bone scan
b. Useful p-surgery (better than MRI) which will always be abnormal
c. When combined with bone scan has specificity in the 90% range, sensitivity in the 70%
range and PP value in the 90% range
d. Low sensitivity for chronic OM of axial skeleton
Ga-67
a. Non-specific
b. Combined with bone scan - sensitivity ~79%, specificity 83-93%
c. Not as useful as Ind-111 WBC scan except for spinal osteo when WBC
scans can be obscured by GI localization of tracer
d. Poorer image quality than bone or WBC scans
d. Useful when combined with bone scan in sorting out infarction (sickle cell disease)
from osteomyelitis
Tc99-Radolableled monoclonal antibodies or Fab fragments that are attached to WBCs
(anti-CD15)
a. Sensitivity 84%
b. Specificity 85% (if delay imaging) (Rubello, Nu Med Comm, 2004)
Streptavidin/In-111-biotin
a. Biotin taken up and accumulates in bacteria
b. In study of 55 patients with vertebral OM: Biotin scan + in 32/34 with infection
(sensitivity 94%) and negative in 19/21 without infection (95% specific) (Lazzeri, Eur J
Nucl med, 2004)
PET scanning (FDG)
a. Most useful in detection of chronic OM of spine
b. limitations are use patients with diabetes and cancer and those with recent bone surgery
or trauma (early bone healing will give + PET scan) (Pineda, Inf Dic Clin of N America,
2006)
1. Cultures
a. Gold standard is open bone biopsy for histopathology and culture.
b. Needle biopsy has a sensitivity of 87% and a specificity of 93%. However, in the postoperative or post-trauma setting its performance is compromised. Histopathology of
needle biopsies can increase sensitivity for diagnosis of osteomyelitis even if a specific
organism is not identified
c. Superficial or sinus tract cultures correlate poorly with bone cultures in most studies (<
50%). One study (Perry, 1991) found a 62% correlation between wound swab and
operative specimen cultures and a 55% correlation between needle biopsy and operative
specimen cultures. Even better correlations demonstrated for monomicrobial infections
(80 and 76%) and S. aureus infections (69 and 74%). Another study (White, 1995)
showed only 42% sensitivity of needle biopsy cultures but 84% sensitivity when culture
and histopathology considered. Bottom line: don't trust sinus cultures unless its a single
organism or S. aureus.
Treatment
Acute hematogenous osteomyelitis
1. If treating before extensive bone necrosis occurs - antibiotic therapy for 4 to 6 weeks
achieves high cure rates.
2. If acute osteomyelitis is unresponsive to abx, may need surgical decompression of
intramedullary or subperiosteal pus. Other indications for surgery are the presence of
a soft tissue abscess or joint involvement.
3. Vetebral osteomyelitis: surgery reserved for cord decompression, spine stablization or
to drain paravertebral abscesses.
Contiguous focus osteomyelitis
4. Recurrence rates are 20 to 30%
5. Combined surgical and medical approach needed. Guiding principles are
debridement of necrotic bone and prolonged antibiotic therapy. Best results may be
with serial debridements (average of 4), prolonged IV antibiotics (4 to 6 weeks)
followed by oral antibiotics (Eckardt, 1994).
6. Surgical principles are
Removal of all necrotic tissue
Dead space obliteration (antibiotic beads – later replaced by bone grafts, bone
grafts, muscle flaps)
Soft tissue coverage of bone to promote re-vasculaturization
Fracture stablization
Best results reported by Patzakis (1993) using the following sequence: debridement
(antibiotics started intraoperatively after cultures taken) with external fixation applied followed by re-debridement and soft tissue transfer 5 days later and bone grafting (if
necessary) performed 6 weeks later. Parenteral antibiotics given for mean of 21 days
followed by oral. Cured 35 (96%) of 36 patients. Recent publication by Schuster (J
Neurosurg, 2000) identified 39/47 patients (no follow-up on 8) who had had bone
allografts placed at the time of surgical debridement for spine infections (4 of 39 were
TB). Follow-up of 17 months: 2/39 had possible recurrent infections.
4. Ilizarov technique (for long bone chronic osteomyelitis) - involves complete resection
of diseased bone leaving a large gap and a cut far up-stream of the necrotic bone which
creates an intermediate fragment which is slowly translocated (by means of guidewires
attached to an elaborate external fixation device) leading to the growth of new bone along
the axis thus, filling the gap.
5. Antibiotics: Ideally, antibiotic selection is based on reliable culture and sensitivity
results. In general, antibiotics are initially given parenterally. After 2 weeks of
intravenous therapy antibiotics may then be given orally provided an acceptable oral
regimen is available, the infection is responding to therapy and the patient is reliable or
can be monitored closely. Two studies of Staphylococcus osteomyelitis involving
prosthetic devices documented the effectiveness of rifampin/quinolone regimens without
prosthesis removal.
i Drancourt, 1993: treated patients with rifampin (900 mg/d) and ofloxacin (600
mg/d). Hips - treated for 6 months with unstable prothesis removal at 5 months
(42% removed) - 81% cured, knees - treated for 9 months with prothesis removal
at 6 months if needed (60% removed) - 69% cured and bone plates treated for 6
months with plate removal at 3 months if needed (50% removed) - 69% cured.
Note: Most (8 of 11) failures occurred in those without device removal. Mean
duration of infection in all patients - 16 months.
ii Zimmerli, 1998: First (only) randomized controlled trial for treatment of
osteomyelitis (Staphylococcal implant related infections). N=33, culture proven
Staphylococcus infections and stable implants (8 hips, 7 knees and 18 plates or
rods). All treated with initial debridement (without removal of implant) and 2
weeks of rifampin and either flucloxacillin or vancomycin followed by either
cipro-rifampin or cipro-placebo. Cure rates: 12/12 for cipro-rifampin vs 7/12 for
cipro-placebo (5/7 dropouts eventually treated with rifampin-cipro were also
cured). Note - median duration of symptoms was only 4-5 days with maximun of
21 days.
iii Ceftriaxone for osteomyelitis: Study by Guglielmo (2000); 22 patients, all
received 1-2 weeks of either nafcillin, cefazolin or vancomycin prior to
ceftriaxone, all had native bone infection or had prosthesis removed at the start of
therapy. Treated with ceftriaxone at 2 grams/day for 4-5 weeks. Results: 17/22
cured, 2/22 indeterminate, 3/22 failed (all 3 had necrotic bone that could not be
removed).
iiii Linezolid: Results of Compassionate Use Experience (Rayner, 2004): Only
22 of 55 cases were considered evaluable (for unclear reasons). Six months post
treatment: cure rate 82% (18/22), for infections with MRSA 64% (7/11).
Another prospective study reported 100% (11/11) success (Rao, 2004) Marrow
toxicity (mostly thrombocytopenia) in 7-8% and rarely irreversible peripheral
neuropathy (Falagas, Int J Antimirobial Agents, 2007). Recent study of linezolid
in children (most with MRSA) – 11/13 cured with linezolid for a month – but all
had received vanco for ~ 1month prior and linezolid was used as “step down
(oral) therapy (Chen, Ped J of Infec Dis, 2007).
v. Daptomycin??: Preliminary study of Daptomycin for foot and ankle OM
(Holtom, 2007). 25 patients, MRSA in 15/25. At short follow-up (2 months)
19/25 resolved, 3/25 improved and 3/25 no response. 4/25 patients with implant
related infection cured (all had implant removed). More recent study – POST
HOC analysis of patients with S aureus(mostly MRSA) bacteremia treated with
either dapto or vanco who had OM – cure rates: dapto 14/21 (67%) Vs vanco 6/11
(55%) (Lalani, JAC, 2008).
vi. Oral therapy:
Daver, J Infection, 2007;54:539-44
Retrospective review of 72 patients with S. aureus osteomyelitis
Two groups:
Group I: IV therapy for > 4ks
Group II: IV therapy for < 4 wks followed by oral therapy
IV Rx was mostly vanco or beta-lactams, PO Rx was mostly
rifampin + quinolone or TMPSMX or clindamycin
Cure rates
IV Rx = 69%
Oral Rx = 78%
Cure rates similar regardless of time of IV Rx
Rifampin/Vanco combo was inferior to Rifampin/other combo
Cure rate for MRSA 65% vs 83% for MSSA
Corti, Arch Dis Child, 2003
N=103
Acute hematogenous osteomyelitis
IV Abx of > 2.5 weeks provided no added benefit when total duration of
treatment was at least 6 to 7 wks
LeSaux, BMJ Inf Dis, 2002
Review of 12 prospective cohort studies
Hematogenous osteomyelitis
Cure rate of 95% with < 7 days of IV + mean of 32 days of oral Abx (betalactam or clindamycin)
Zaoutis, Pediatrics, 2009
Retropspecitve cohort study of 1969 children
Treatment assigned based on discharge code regarding central catheter
placement – if no DRG for this then it was assumed they were treated with
oral meds
Failure rate 5% with IV therapy Vs 4% with oral therapy
3.4% of children on IV therapy were readmitted with catheter
complications
6. Osteomyelitis accompanied by a poor vascular supply:
If the vascular insufficiency is the result of correctable large vessel disease, revascularization surgery should be performed.
If re-vascularization is not possible or unlikely to correct tissue hypoxia then the
patient may be offered amputation or chronic suppressive therapy with oral
antibiotics, although in the latter case amputation is often ultimately necessary.
Finally, hyperbaric oxygen treatment may be of benefit in those cases where tissue
oxygen tension is low and not amenable to treatment with a tissue flap.
Hyperbaric oxygen leads to improved tissue oxygenation that enhances PMN and
macrophage activity and augments collagen synthesis and wound healing. A nonrandomized (but controlled) study found no benefit of hyperbaric oxygen on
outcomes, case series are more encouraging.
7. Cierny-Mader staging
Stage 1 – Children without hardware are often treated with antibiotics alone. All
patients with rods in place require removal. Adults without hardware may require
medullary reaming.
Stage 2 – Debride to bleeding bone and antibiotics
Stage 3 – Follow principles of removal of necrotic bone, elimination of dead
space and soft tissue coverage plus antibiotics
Stage 4 – Same as stage 3 plus fracture stabilization.
Prosthetic joint infection
1. Microbiology: CNS 30-43%, S. sureus 12-13%, polymicrobial 10-11%,
streptococci 9-10%, GNB 3-6%, enterococci 3-7%, anaerobes 2-4%, culture
negative 11%
2. Clinical
a. Early: < 3 months (pain, erythema, fever, drainage)
b. Delayed: 3-24 months (pain and loosening)
c. Late: > 24 moths (pain and loosening)
3. Diagnosis
a. Synovial fluid formula: > 1700 wbc (sensitivity 94%, specificity 88%), or
> 65% PMN (sensitivity 97%, specificity 98%)
b. Synovial fliud Gm stain: sensitivity 26%, specificity 97%
c. Culture: synovial fluid 45-100%, peri-prosthesis tissue 65-94%
4. Treatment
a. Rifampin useful when added to quinolone for staphylococcus infections
b. Surgical options: 1) debridement with retention, 2) single stage
replacement, 3) two stage replacement, 4) resection arthroplasty, 5)
suppressive antibiotics
i. Debridement with retention: symptoms for < 3 weeks, stable
implant easily treated organism: success 82-100%
ii. Single stage replacement: symptoms for > 3 weeks, soft tissue in
good shape, no co-morbidities, easily treated organism, success in
86-100% (more commonly done with hips)
iii. Two stage replacement: if above conditions are not met. Time
between surgeries 2 to 6 weeks (for tough to treat organisms,
MRSA, resistant GNR, enterococci, fungi – delay should be 6 to 8
weeks). Stop abx 1 to 2 weeks before 2nd surgery – if cultures
taken at 2nd surgery are negative – can stop antibiotics, if cultures
are positive – treat for 3 months total (if knees – 6 months)
iv. Resection arthroplasty – for serious infection in patient with
anatomical, medical or social (IVDU) condition that prevents
prosthesis replacement
v. Supressive antibiotics – in patient at high risk for surgical
complications (TMP/SMX or tetracycline commonly used)
c. Duration of abx: 3 months minimum, 6 months for knees
d. Treatment with retention of prosthesis
i. Meehan, CID, 2003
ii. Prosthetic Joint Infection with Penicillin Susceptible Streptococci
iii. N=19
iv. Presented between 52 and 4788 days post-op
v. All prostheses were well fixed
vi. All were debrided within 4 days of symptoms
vii. Cure rate at 1 year: 89%
Diabetic foot osteomyelitis
1. Present in up to 2/3 of patients with diabetic foot ulcers
2. Pathophysiology: Multifactorial. Neuropathy most important risk factor. Decreased
sensation permits local trauma to go unnoticed, motor neuropathies lead to gait
disturbances and the development of pressure ulcers, autonomic neuropathy impairs
sweating and promotes dry cracked skin that leads to bacterial invasion. Many
patients also have peripheral vascular disease causing decreased tissue oxygen tension
which compromises antibacterial activity. Finally, diabetes is associated with
impaired PMN chemotaxis, phagocytosis and superoxide production and intracellular
killing.
3. Diagnosis:
Clinically: Larger (> 2cm, 92% specificity) and deeper ( > 3mm) associated with
osteo
Probe to bone – 66% sensitivity and 85% specificity
- recent large study (Lavery, Diabetes Care, 2007), N=199
(30 with osteo) demonstrated sensitivity of 87%, specificity
of 91%, PPV only 57% (due to low prevalence of osteo
cases) but NPV 98%
ESR > 70 – 100% specificity (only 28% sensitivity)
Imaging:
MRI sensitivity > 90%, specificity > 80% (out performed bone scans, WBC
scans and plain radiography in large meta-analysis, Kapoor, Arch Int Med, 2007).
Classic appearance – marrow is hypointense on T1 and hyperintense on T2
Distinguishing osteo from Neuropathic arthropathy (Charcot’s arthropathy)– on
MR: Osteo is almost always contiguous to ulcer and usually affect the calcaneous
or malleoli. Neuropathoic arthropathy usually affects the tarsal-metatarsal joints
or metatarsal-phalangeal joints- the findings on the MR are joint-centered
(Donavan, Radiol Clin N Am, 2008)
Leukocyte scans (indium and technetium): sensitivity 85%, specificity 75%.
111-In WBC scans used with bone scans or MRI perform best (also help to
distinguish osteomyelitis from soft tissue infection and non-infectious destructive
bone disease – Charcot’s neuropathic osteoarthropathy.).
Radiolabeled anti-granulocyte Fab fragments – promising, sensitivity 67-90%,
specificity 75-85%
Bone biopsy: The gold standard. Percutaneous needle biopsy has sensitivity of up to
92% (culture and histopathology)
4. Microbiology: most are polymicrobial; S. aureus (40%) > aerobic gpc (streptococci
30%, CNS 25%) > aerobic gnr (40%) > anaerobes (anaerobes more likely to play a
role in large destructive infections). Poor correlation between bone and soft tissue
results. If bone cultures not available: must cover S. aureus, otherwise individualize
treatment.
5. Treatment: best approach is aggressive surgical debridement/resection of involved
bone, revascularization (if needed) and long-term appropriate antibiotics.
a. Several recent retrospective studies suggest antibiotics alone (or with minimal
debridement can arrest the infection in 2/3 of cases (summarized in Jeffcoate,
CID, 2004)
b. Linezolid??: R,MC,OL trial or linezolid vs amp/sulbactam-amox-calvulinic
(Lipsky, CID, 2004): 77 cases of osteo
a. Cure rates of 61% (27/44) vs 69% (11/16) in evaluable patients
b. 5% of the linezolid patients received aztreonam as well, 4.6%
developed anemia, 3.7% developed thrombosytopenia
6. Randomized and non-randomized studies support the use of hyperbaric oxygen
(HBO) in diabetic foot ulcers (not osteomyelitis specifically). HBO is associated with
more complete healing and lower amputation rates.
Pyogenic Vertebral Osteomyelitis
Large study by McHenry (CID, 2002): retrospective study with average follow-up of 6.5
years, n= 253!
1. Clinically
i.
Location: 28/255 cervical, 78/255 thoracic, 150/255 lumbar-sacral
ii.
Motor deficits associated with cervical location, diabetes, age > 50
iii.
Time to diagnosis (after symptoms): median of 1.8 months
2. Outcomes:
i.
146 (57%) recovered
ii.
80 (31%) qualified recovery (left with pain or neurological deficits)
iii.
29 (11%) died
iv.
Adverse outcome associated with motor deficits at presentation, longer
time from symptoms to diagnosis, hospital acquisition (weighted for spinal
surgery, trauma victums)
3. Relapse:
i.
36 (14%) relapsed
ii.
29/30 - the same organism
iii.
Relapse risk associated with recurrent bacteremia, chronic draining
sinuses, paravertebral abscess, gibbous deformity and involvement of
greater than 3 contiguous vertebral bodies
4. Author recommends: diagnose it early (use MRI), treat it longer (3 to 6 months)
Kowalski, TJ CID, 2007: Retrospective study of 30 patients with early vertebral OM and
51 with late disease (> 30 days post surgery)
Early onset infection – 2 yr disease- free survival 71%. If given suppressive oral
therapy (median duration 303 days) after initial debridement – cure increased to
80%. Without suppressive therapy cure rate 33%
Late-onset infection – 2 yr disease free survival 66%. If implant removed, cure
increase to 84%, without removal 36%
Problems with paper – retrospective study, not randomized, no multivariate
analysis of risks for failure
Livorsi, DJ, J of Infection, 2008: Retrospective review of 35 patients with hematogenous
vertebral osteomyelitis due to S aureus. 57% due to MRSA
Mean duration of treatment 62 days
19/20 with MRSA received Vancomycin and 13/20 received rifampin at some
point in their treatment course (mean duration of rifampin Rx 24 days), 9/20
received oral therapy after vancomycin (gati – 5, TMPSMX - 3, linezolid -1)
5 relapsed (failures) (MRSA -2, MSSA – 3)
Factors associated with relapse – undrained abscess. Trend for failur in those not
on rifampin
6. Follow-up assessment: MRI Imaging to assess cure: Kowalski, Am J
Neuroradiology, 2007:
1. Follow-up MRI showed: 1. Loss of vertebral body height, 2. Less epidural
enhancement, 3. Less epidural abscess compared to baseline scans
2. No single MR finding was associated with clinical cure or failure.
3. Important point is that worsening MR findings did not signal clinical failure
Skeletal Tuberculosis
1. Pathogenesis: In developed countries skeletal TB is a disease of adults and represents
reactivation of an old focus of infection. In the developing world mast cases of
skeletal TB occur in patients who acquired their infection within a year and, thus,
many infections develop in childhood. Many patients give a history of recent trauma
to the involved area.
2. Skeletal TB accounts for 35% of cases of extrapulmonary TB and 2% of all cases of
TB
3. Clinically:
Indolent course, average duration of symptoms prior to diagnosis 16 to 19 months.
Local swelling, pain, fluctuance; systemic symptoms (fever, sweats, etc) often
absent.
Pulmonary disease present in 30%. PPD+ in > 85%
Pott’s disease (tuberculous spondylitis) responsible for 1/3 of cases of skeletal TB.
Infection begins in the anterior aspect of the vertebral body leading to
anterior collapse and spread of the infection along the anterior ligament
Most cases involve the lumber and lower thoracic spine
50% of cases have associated abscesses (if calcified is diagnostic for TB)
50% have weakness or paralysis at the time of presentation or during Rx
50% associated with disc involvement
50% without disc involvement are younger and more likely to have other
skeletal lesions
77% have epidural involvement by MRI (Pertuiset, 1999)
Other bones: any bone; weight bearing, flat, ribs - relatively unique to TB
Diagnosis: AFB stain and culture of biopsy specimen (sensitivity ~85%)
4. Treatment:
Chemotherapy, duration: 9 to 18 months of therapy, although recent studies
suggest that 6 months of therapy, when combined with surgery, is as effective as
longer course of antibiotics
Debridement of abscesses will lead to faster resolution and less kyphosis in those
with severe disease at presentation.
Criteria for surgical intervention in Pott’s: neurological deficit, spinal instability,
cervical spine disease, failure of medical therapy, non-adherence to medical
therapy.
5. Sequential imaging studies may show apparent worsening of the infection for the first
6 months, despite clinical improvement, and should not be interpreted as a failure of
treatment.
INFECTIOUS ARTHRITIS
Non-gonococcal bacterial
Pathogenesis:
1. Usually hematogenously acquired - synovium has no basement membrane, abundant
vascular supply and is easily seeded.
2. Direct inoculation - contiguous osteomyelitis, intra-articular injection, trauma,
prosthetic joint replacement.
3. Proteolytic enzymes from PMNs lead to cartilage and bone destruction, increased
inflammation and pressure. Later, proliferating synovial cells invade the cartilage-bone
matrix.
4. Post infectious arthritis (not reactive) may occur after sterilization of joint - may be
due to persistent microbial antigens or exo- or endotoxins.
Microbiology:
1. S. aureus is most common (> 40% of all cases, > 80% of cases with rheumatoid
arthritis).
2. Streptococci (group A but also nongroup A - B,C,G).
3. GNR (E. coli and P. aeruginosa) becoming more common (IVDU,
immunocompromised and the elderly). H. influenzae formerly common in infants.
4. S. pneumonia - common in the pre-antibiotic era, now ~ 10%.
5. Coagulase negative staph - prosthetic joints.
6. No pathogen identified in 10 to 20%.
7. Mycobacterial and fungal (especially in HIV infected persons).
2. If polyarticular, and not GC, less likely to be S.aureus and more likely to be H.
influenza, or one of the pyogenic strep (A, B, C, G).
3. Prosthetic joints: if infection due to inoculation at time of surgery: CNS,
corynebacterium, S. aureus. If due to hematogenous seeding: S. aureus >
streptococci, GNR and anaerobes
Risk factors:
1. Phagocytic defects (CGD and Chediak-Higashi).
2. Other: hypogmmaglobulinemia, cancer, cirrhosis, steroids, old age, diabetes,
hemophilia (hemarthrosis), sickle cell disease
3. Chronic arthritis - especially rheumatioid arthritis.
4. Recent joint trauma.
5. IVDU, indwelling catheters.
Clinically:
1.Usully monoarticular: knee (50%) > shoulder, wrist, hip (children), elbow and
interphalangeal joints, IVDU - sternoclavicular joints. More indolent presentation in deep
joints (hip)
2. Most often a source is evident, BC positive in 30 to 50%, joint fluid culture positive in
85-95%.
3. Most (> 70%) are febrile, leukocytosis in 60%, elevated ESR in 90%
Diagnosis
1. Joint fliud - WBC 50,000 to 200,000 (90% polys), low glucose.
2. Gram's stain+ 75% (staph), 50% (GNR).
3. Culture + in 90% of cases.
4. CT and MRI scans helpful for SI and sternoclavicular joints and for demonstrating
effusions and associated osteomyelitis. US is helpful in demonstrating joint effusions in
deep joints (hip).
Treatment
1. Antibiotics (if Gram's stain negative - choose antibiotics that will cover S. aureus and
streptococci), drainage and rest.
2. Antibiotic - duration: 2 to 6 weeks (depends on presence of osteomyelitis, chronicity
of infection, identification and susceptibility of organism). Shorter courses needed for
streptococci and H. influenza and longer therapy for S. aureus, enterobacteriaceae and
pseudomonas
Peltola, CID, 2009:
R,MC trial of 130 children with septic arthritis – Rx with either 10 or 30 days of
clindamycin or first gen cephalosporin
Five in 10 day group had their treatment had their treatment extended to between
17 and 21 days and four in the 30 day group had their treatment extended to
between 37 to 93 days
~90% follow up at one year post infection – only 1 child had relapsed (in the 30
day group)
3. Drainage: repeat closed needle aspiration (usually for 5 to 7 days). Arthroscopy and
open drainage necessary for: hips, sometimes shoulders, gram-negative infections, if
osteomyelitis is present and if pus is thick and cannot be aspirated.
4. After acute phase of infection - passive range of motion should be started ASAP.
Gonococcal
Disseminated gonococcal infection (DGI) develops in 0.5 to 3% of cases of mucosal GC
and is the most common cause of infective arthrits in the US
Pathogenesis:
1. Specific GC strains are more often found in patients with DGI: more resistant to
complement, more sensitive to penicillin, transparent colony type (lack Protein II), have
specific nutritional requirements (arginine, hypoxanthine and uracil - AHU) and belong to
serotype P.IA.
2. The dramatic response to antibiotics and the lack of response to steroids argues for
direct infection causing disease despite the low rate of recovery of GC from joint fluid.
3. However, in animal models, injection of killed GC into joints creates an arthritis
indistinguishable from that caused by live organisms.
Risks:
1. Complement deficiency (C7 and C8), women > men (and especially while pregnant or
during menses).
Clinically:
1. Most are young healthy adults.
2. Initially - migratory polyarthralgia, fever, tenosynovitis and dermatitis (small
maculopapular, pustular, necrotic or vesicular lesions on the trunk and extremities are
characteristic -bullae, purpura, erythema mutiforme have also been reported), fewer than
30, face is spared
3. Tenosynovitis picture in 2/3 (usually hands and fingers), polyarthritis in 50%.
4. Mucosal infection is usually asymptomatic.
5. BC positive is < 20% and joint fluid culture positive in < 50% of all cases (more + in
purulent arthritis), joint fluid Gram's stain+ < 25%, genitourinary cultures are + in 80% of
cases of DGI. PCR to detect GC in joint fluid probably better test (sensitivity of ~80%,
specificity of > 95%).
Treatment:
1. Initial therapy with parenteral 3rd generation cepahlosporin (e.g. ceftriaxone) (or a
penicillin if susceptible) until 24 to 48 hours after improvement - followed by oral
therapy (cefixime or a quinolone) to complete a week of treatment.
2. Effusions should be serially aspirated but open drainage rarely needed.
Reactive Arthritis
Inflammatory but sterile arthritis
Pathogenesis:
1. Studies have demonstrated both bacterial antigens and DNA in synovial tissue and
fluid in post-enteric reactive arthritis.
2. More compelling evidence for the presence of Chlamydia in synovial tissue and fluid
(antigens, DNA, RNA and whole organisms [by EM]) in post-genital reactive arthritis.
Chlamydia has been identified as the preceding infection in 42 to 69% of patients with
reactive arthritis in the US.
3. HLA-B27 may present bacterial antigens in a fashion that often leads to crossreactivity to host tissue.
4. HLA-B27 shares homology with certain bacterial proteins - suggesting serologic
cross-reativity
Clinically:
1. Asymmetric, additive polyarthritis predominantly in large joints of the lower
extremities. Usually occurs 1 to 2 weeks after an infection. Knees 70%, ankles, 57%,
wrists and fingers 45%, toes 35%. SI joints common in Chlamydia associated RA
2. Extra-articular features: skin and eye involvement, enthesitis (especially in heels),
dactylitis (sausage digits)
3. Reiter's syndrome: triad of conjunctivitis, urethritis and arthritis occurs in minority of
patients.
4. HLA-B27 association: with sacroiliitis (54%), post-enteric (50-80%), post-genital
(90%). Not associated with rheumatoid factor.
5. Post-enteric (Salmonella, Shigella, Yersinia and Campylobacter infections):
M=F
Better prognosis (complete resolution in 80 to 90% - less after Salmonella) than
post-genital
Recurrent attaks unusual after Yersina-associated disease
6. Post-gential (Chlamydia):
M>F
More relapses than post-enteric (re-infection?)
7. Associated with inflammatory bowel disease (10 to 20%), often occurs when IBD
flares, usually large joint - oligoarthrits, minimally symptomatic.
7. Duration of disease is 3 to 5 months with ~15% developing chronic disease.
8. HIV associated reactive arthrits - resembles typical reactive arthritis, psoriatic
arthritis or undifferentiated spondyloarthropahy - becoming less common in
developed countries where HAART is available.
Treatment:
1. Antibiotics not helpful in post-enteric reative arthritis.
2. Antibiotics (e.g. tetracyclines) for 1 to 3 month may benefit patients with post-genital
(post Chlamydia) reactive arthritis. Probably depends on the state of Chlamydia in the
joint. If organism is in persistent state (not the vegetative state) it may express different
set of genes and not be susceptible to antibiotics that have activity against organisms in
the vegetative state. This may account for the variable response of Chlamydia-associated
RA.
3. Prompt treatment of genital chlamydia infection may reduce the incidence of STD
associated reactive arthritits.
3. Anti-inflammatory agents: NSAIDs, methotrexate and azothioprine, intra-articular
steroids. Sulfasalazine may be of benefit, especially in reactive arthritis associated with
inflammatory bowel disease.
Prosthetic joint (see Osteomyelitis section above)
1. 0.5 to 2 percent rate of infection over 10 years, but 5 to 10% in prosthetic joint
revisions.
2. Early (within 12 weeks) likely due to operative contamination, later infections the
result of bacteremia with seeding of the joint.
3. Microbiology: coagulase negative staph (40%) > S. aureus (20%) > GNR,
polymicrobial and anerobic infections > fungi. Early: CNS and S. aureus. Late: S.
aureus, streptococci, GNR and anaerobes.
4. Indolent pain, erythema and drainage = early. Pain = late. Fever uncommon.
5. Radiographic evidence of loosening in 66% of late and < 50% early infections.
6. Joint aspiration necessary for diagnosis, histopathology also helpful (especially* when
cultures are negative).
7. Treatment: see Osteomyelitis section.
Other infectious and non-infectious causes of arthritis
Mycobacterial - insidious onset, single (usually weight-bearing) joint is classic
description. More recent reports are of older and immunosuppressed individuals
presenting with systemic symptoms and multiple joint involvement with periarticular cold
abscesses. Oligoarticular disease is also associated with HIV. 50% have concurrent
pulmonary disease, 90% are PPD+. Joint fliud: AFB stain + in 20%, culture + in 80%
and synovial culture + in 90%. Treatment is medical unless there is significant joint
destruction or instability that requires surgery.
Fungal - insidious onset, single joint (or oligoarticular), associated with HIV.
Viral (Rubella, Mumps, Parvovirus, Hepatitis B, Hepatitis C, HIV) - polyarthritis, fever
and rash.
Lyme - local epidemiology, history of erythema migrans, tick bites.
Infectious endocarditis.
Crystal disease - history of same in past, crystals in joint fluid.
CVD - RA, Still's disease, SLE, vasculitis, psoriasis.
Rheumatic fever - in adults: arthrits and fever >> carditis, nodules and rash; may be
additive rather than migratory arthritis; check ASO titers.
Poststreptoccal reactive arthritis – shorter incubation than that seen in RA, more
involvement of small joints and axial skeleton, protracted course compared to RF, poor
response to ASA and NSAIDS, low incidence of carditis
Osteonecrosis of the mandible – associated wilth bisphosphonate treatment
FMF - usually in childhood; recurrent bouts of fever, arthritis, abdominal and pleuritic
pain.
Cancers - leukemia in children.
Sarcoidosis
Kawasaki's
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1. Cunha, BA. Osteomyelitis in elderly patients. Clin Infect Dis, 2002;35:287-93.
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4. Lew zDP and Waldvogel FA. Osteomyelitis.
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d. Lavery LA, et al. Probe to Bone test for diagnosis diabetic foot OM. Diabetes care,
2007, 30: 270-74.
e. Arnold SR, et al. Changing patterns of acute hematogenous OM and septic arthritis:
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1. Butalia S, et al. Does this patient with diabetes have osteomyelitis of the lower
extremity. 2008. JAMA;299: 806-13.
2. Chen CJ, et al. Experience with linezolid therapy in children with osteoarticular
infections. 2007. Ped J Infec Dis;26:985-88
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1. Dinh, et al. Diagnostic accuracy of physical examination and imaging tests for
osteomyelitis underlying diabetic foot ulcers: meta analysis. 2008. CID; 47:517-27
2. Donovan and Schweitzer. Current concepts in imaging diabetic pedal osteomyelitis.
2008. Radiol Clin N Am;46:1105-24
3. Peltola, et.al. Prospective, randomized trial or 10 days Vs 30 days of abx treatment for
childhood septic arthritis. 2009. CID;48:1201-10
4. Livorsi, et al. Outcomes of treatment for hematogenous S. aureus vertebral
osteomyelitis in the MRSA era. 2008. J of Infection;57:128-31.
5. Zaoutis, et.al. Prolonged IV therapy Vs early transition to oral abx therapy for acute
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2008. Arch Int Med. 168:805-819