Transcript Non_Gonococcal_Septic_Arthritis

NON-GONOCOCCAL
SEPTIC ARTHRITIS
Outline
2








Introduction
Risk Factors
Pathogenesis
Microbiology
Clinical Features
Treatment
Prognosis
Special Cases
Introduction
3

Infectious arthritides







Non-gonococcal septic arthritis
Gonococcal arthritis
Lyme disease
Viral arthritis
Fungal arthritis
Osteomyelitis
Bacterial joint infection are serious
 Most
rapidly destructive form of acute arthritis
 Significant mortality (10-15%) and morbidity (25-50%)
 Irreversible loss of function in up to 50% of patients
Hochberg et al. Chapter 96. Copyright ©2008 Elsevier Inc.
Septic Arthritis
4

Incidence
2-6/100,000 in general population
 30-60/100,000 in patients with RA and/or joint prostheses


Despite advances over last 25 years, fatality rate unchanged


Most important prognostic indicator


Although decreased number of prosthetic joint infections,
prosthetic joints remain most common cause of joint infections
Speed of diagnosis and treatment
General rule

If treated within 7 days, patients generally do well
Hochberg et al. Chapter 104. Copyright ©2010- Elsevier Inc.
Risk Factors for Septic Arthritis
5







Recent joint surgery (+LR 6.9, 95% CI 3.8-12.0)
Age > 80 years (+ LR 3.5, 95% CI 1.8-7.0)
Prosthetic joint (+LR 3.1, 95% CI 2.0-4.9)
Skin infection (+LR 2.8, 95% CI 1.7-4.5)
Diabetes mellitus (+LR 2.7, 95% CI 1.0-6.9)
Preexisting RA (+LR 2.5, 95% CI 2.0-3.1)  TNF-I (?)
Others
Impaired immune system (cirrhosis, malignancy)
 Renal failure and hemodialysis
 Hemophilia
 Indwelling catheters
 IVDA & alcoholism

Margaretten ME, et al. JAMA 2007; 297(13):1478-1488.
Pathogenesis
6
70%
Arthrocentesis
or Arthroscopy
20%
Hochberg et al. Figure 96.1. Copyright ©2008 Elsevier Inc.
Gilliland, WR. Rheumatology Secrets, 2nd ed, ed. West 2002. Hanley & Belfus: Philadelpha, pp. 281-289.
Pathogenesis
8

Bacteria enter joint, deposit on synovial membrane

Produce inflammatory response


Exudation of bacteria, cells, and proteins into SF


Synovial tissue proliferates, becomes tender, blood flow increases
No limiting basement membrane
Within 5-7 days
Joint becomes swollen
 Elastase, collagenase liberated from PMNs, synovial cells
degrade cartilage
 Infection, inflammation can spread to subchondral bone
 Pressure necrosis from large effusions result in further cartilage
and bone loss

Pathogenesis
9

Bacterial DNA and toxins may have deleterious effect
 Staphylococcal
toxic shock syndrome toxin (TSST)-1
 Staphylococcal enterotoxins

Adhesins on bacteria probably important (MSCRAMMs)
 Important
virulence factor
 Mediate adherence of bacteria to intraarticular proteins
 Fibronectin,
laminin, elastin, collagen, hyaluronic acid, and to
prosthetic joint materials
 Likely
why S. aureus causes most septic arthritis
Hochberg et al. Chapter 96. Copyright ©2008 Elsevier Inc.
Pathogenesis
10
Microbiology
11

Gram-positive cocci (75-80%)

S. aureus most common in native and prosthetic joints
Most common etiologic agent in 40-70% of cases
 Increasing incidence of CA-MRSA

Streptococci
 S. epidermidis common in prosthetic joints, rare in native joints


Gram-negative bacilli (10-20%)
Elderly who are predisposed to systemic GNR infections
 Immunocompromised (e.g. SLE patients)


Anaerobes (1%)

Occur in prosthetic joints, rare in native joints
Gilliland, WR. Rheumatology Secrets, 2nd ed, ed. West 2002. Hanley & Belfus: Philadelpha, pp. 281-289.
Hochberg et al. Chapter 96. Copyright ©2008 Elsevier Inc.
Microbiology of Septic Arthritis
12
Organism
Clinical Clues
Staphylococcus aureus
Healthy adults, skin breakdown, previously damaged joint (e.g. RA),
prosthetic joint
Streptococcal species
Healthy adults, splenic dysfunction/asplenia
Neisseria gonorrhea
Healthy adults (particularly young, sexually active), F >> M’s,
associated tenosynovitis, vesicular pustules, late complement
deficiency, negative SF culture and gram stain
Aerobic gram negative bacteria
Immunocompromised hosts, GI infection
Anaerobic gram negative bacteria
Immunocompromised hosts, GI infection
Mycobacterial species
Immunocompromised host, recent travel to or residence in an
endemic area
Fungal species (sporotrichosis,
cryptococcus, blastomycosis)
Immunocompromised host
Spirochete (Borellia burgdorferi)
Exposure to ticks, antecedent rash, knee joint involvement
Mycoplasma hominis
Immunocompromised hosts with prior GI tract manipulation
UpToDate®
Joint Distribution
13

Monoarticular (80-90%)
Predilection for single large joint, typically the knee or hip (60%)
 LE >> UE (particularly the knee)
 Always consider septic arthritis in DDx of an acute monoarthritis


Polyarticular (10-20%)
More common in those with preexisting arthritis
 S. aureus is the major pathogen
 May portend a less favorable outcome



>50% mortality rate in RA patients
Aspirate >1 joint when suspected
Clinical Features of Septic Arthritis
14

Joint capsule


Tumor (78%), Rubor, Calor
Severe pain (Dolor) (85%)
 Typically

abrupt onset
Fever (57%)
 Sweats
(27%)
 Rigors (19%)



Inflammatory SF
Leukocytosis (45%)
Elevated CRP/ESR (87%)
Margaretten, ME, et al. JAMA 2007; 297(13):1478-1488.
Diagnosis (no gold standard)
15

Traditional ‘index of suspicion’

Positive Gram stain
OR
Positive culture
OR
Positive synovial biopsy or PCR
OR
Typical clinical syndrome with response to Rx



Arthrocentesis –
Cornerstone of Diagnosis
16

Cell Count
 Progressively
higher SF WBC increases likelihood
<
25,000/μL (+LR 0.32, 95% CI 0.23-0.43)
 ≥ 25,000/μL (+LR 2.9, 95% CI 2.5-3.4)
 > 50,000/μL (+LR 7.7, 95% CI 5.7-11.0)
 > 100,000/μL (+LR 28.0, 95% CI, 12.0-66.0)
 Wide
range depending on timing, abx pre-treatment, etc.
 Typically a preponderance of PMNs
≥
90% (+LR 3.4, 95% CI, 2.8-4.2)
 <90% (+LR 0.34, 95% CI, 0.25-0.47)
Margaretten, ME, et al. JAMA 2007; 297(13):1478-1488.
Arthrocentesis –
Cornerstone of Diagnosis
17



Gram stain (+ in 50-80%)
Wet prep examination for crystals
Culture (+ in majority of NG septic arthritis)
False (-) due to fastidious organisms or recent antibiotics
 Blood culture bottles reduces the false (-) results


Inoculation of bottles should be done in the lab, not at bedside

Synovial glucose, protein, and LDH not helpful

Blood cx’s may id causative agent when SF cx unrewarding
Matthews, CJ et al. Ann Rheum Dis 2007; 66:440-445.
UpToDate®
18
UpToDate®
Pseudoseptic Arthritis
19


First described in 1985 by Call et al.
Acute arthritis (mono-/oligo-) superimposed on
chronic rheumatic disease with associated fever,
inflammatory SF, and (-) culture
 RA
 Gout
 Apatite-related arthropathy
 PsA
 Dialysis-related amyloidosis
 Plant thorn synovitis
 PVNS
 Neuropathic arthropathy
 JIA
 Pseudogout
 ReA
 SLE
 Sickle cell disease
 Transient osteoporosis synovitis of the hip
 Metastatic carcinoma
 Hemarthrosis
Imaging Adjuncts to Diagnosis
20

Plain films


Presence of radiographic changes indicates that infection has
been present for 2-3 weeks or more
Sonography
Useful for diagnosis of effusions, ST fluid collections
 Not useful for evaluating the presence of osseous infection


CT
Detect early osseous erosion, sequestrum, foreign body,
gas formation
 Less sensitive than MRI/scintigraphy for detection of bone
infection

Scintigraphy
21

Useful in identifying multifocal involvement
Hochberg et al. Chapter 96. Copyright ©2008 Elsevier Inc.
MRI with Gadolinium
22

Synovial enhancement in 98%



Joint effusions common (70%)



Due to increased vascularity
Associated with perisynovial edema (84%), synovial thickening (22%)
91% of large joints, 54% of small joints
Absence of effusions in not an absolute (-) predictor
Abnormal bone marrow signal has highest association with
concomitant osteomyelitis


Especially if diffuse and on T1-weighted images
But also had a high false (-) rate
Karchevsky M, et al. AJR 2004; 182:119-122.
Radiologic and Pathologic Changes
(A-B-C-D-E-S)
23
Radiographic Sign
Pathologic Correlate
A
Bony ankylosis
Fibrous or bony ankylosis (end-stage)
B
Osteoporosis
Increased blood flow, inflammatory
cytokines
C
Joint space loss
Pannus with cartilage destruction
D
Joint deformity
End stage of arthritic destruction
E
Erosions
Pannus with bony destruction
S
Joint effusion (the first sign), softtissue swelling
Edema of synovium with fluid
production
Gilliland, WR. Rheumatology Secrets, 2nd ed, ed. West 2002. Hanley & Belfus: Philadelpha, pp. 281-289.
Therapy for Septic Arthritis
24

Prompt treatment !
 Start
antibiotic(s) immediately after samples collected
 Use Gram stain and clinical scenario to make choice
 Broad coverage in debilitated elderly if Gm stain inconclusive

Once organism identified and sensitivities known
 Continue
 Most
with
efficacious agent
 With best safety profile
 And lowest cost
Therapy (no RCTs)
25
Gram Stain Results
Antibiotic
Gram-positive Cocci
Vancomycin (30 mg/kg daily IV in 2 divided doses not to
exceed 2 gm per day unless serum levels monitored)
Gram-negative Bacilli
3rd generation cephalosporin
 Ceftazidime 1-2 gm IV q8h OR
 Cetriaxone 2 gm IV q24h OR
 Cefotaxime 2 gm IV q8h
 If cephalosporin allergy
Ciprofloxacin 400 mg IV q12h OR 500-750 mg PO q12h
 If suspect Pseudomonas
Add Gentimicin 3-5 mg/kg/day in 2-3 divided doses
Negative Gram Stain
UpToDate®2008.
 Immunocompetent
Vancomycin
 Immunocompromised or
traumatic arthritis
Vancomycin plus 3rd generation cephalosporin
Therapy (no RCTs)
26
SF Gram-Stain Findings
Initial Antibiotic Regimen
Gram-positive
Gram-positive cocci in clusters
(presumptive Staphylococcus)
Nafcillin or oxacillin
(add aminoglycoside if IVDA)
Gram-positive cocci in chains
(presumptive Streptococcus)
Nafcillin or oxacillin
Gram-negative
Gram-negative bacilli
Nafcillin or oxacillin/aminoglycoside†
Gram-negative diplococci
(presumptive gonococcus)‡
Ceftriaxone or cefotaxime
†All with prosthetic joints, IV’s, or recent hospitalization are at risk for MRSA infection and should receive
Vanc until cx results available, regardless of Gram-stain results.
‡In the absence of definitive Gram-stain results, a reasonable empiric regimen for the adult with possible
septic arthritis is the combination of naf-/oxacillin with a cephalosporin (3rd- or 4th-generation). An AMG
should be added in IVDA. Vanc should be substituted for nafcillin/oxacillin if MRSA is a possibility.
Ho, G Jr. Septic Arthritis. Primer on the Rheumatic Diseases, 3rd ed, ed. Klippel. Springer: NY, 2008. Pages 271-276.
How Long to Treat? It Depends…
27
Clinical Scenario
Duration of Treatment
Uncomplicated native joint infections
2-4 weeks IV, then 2-3 weeks PO
Difficult to treat pathogens
3-4 weeks IV
Serious infection in compromised host
4-6 weeks IV
Bacteremia with secondary arthritis
4 weeks IV
Prosthetic joint infections
Protracted course
Therapy (no RCTs)
28

Drainage of purulent material
 Goals:
 Relieve pain
 Eradicate
infection
 Hasten recovery of lost function
 Can
be done surgically or via closed needle aspiration
 Controversy over
which should be employed
 Only one paper compares the two


Retrospective analysis with small number of cases
Results suggested needle aspiration appeared, in general, to be
preferable as the initial mode of treatment, but results did not have
statistical significance
Matthews, CJ et. Ann Rheum Dis 2007; 66:440-445.
Therapy (no RCTs)
29

Overall recommendation is to involve Orthopedics
 To
help facilitate best choice of drainage procedure
 Arthroscopy often preferred for knee and shoulder
 Initial open drainage may be necessary for hip

Immobilization of affected joint initially

PT/OT as soon as patient can tolerate

Effective analgesic medication

NSAIDs for post-infectious synovitis
When is Surgical Drainage Necessary?
30








Infected hip joints, probably shoulder joints
Vertebral osteomyelitis with cord compression
Needle aspiration technically difficult
Inability to remove purulent fluid by needle drainage
Sterilization of the joint fluid is delayed (>7 d)
Joint already damaged by preexisting arthritis
Associated osteomyelitis requiring surgical debridement
Arthritis associated with foreign body
Gilliland, WR. Rheumatology Secrets, 2nd ed, ed. West 2002. Hanley & Belfus: Philadelpha, pp. 281-289.
31
Diagnostic approach to
suspected bacterial arthritis
UpToDate®
Prognosis
32


Morbidity 30%, Mortality 10-15%*
Factors portending poor outcome
Young age, old age
 Virulent microorganisms
 Delay in diagnosis/treatment
 Presence of underlying joint disease (e.g. RA) or prosthetic joint
 Infection of particular joints (shoulder, hip)
 Polyarticular*
 Positive blood cultures*
 Comorbid conditions (RA, IS, renal or cardiac disease)*

Carola, J et al. Arthritis Rheum 1997; 40(5): 884-892.
Ho, G Jr. J Rheum 1993; 20: 2001-2003.
Why Worse Prognosis in RA?
33



Previously damaged joints
Immunosuppression
Steroids may blunt symptoms
 May
be mistaken for a “flare” of RA

Gram positive organisms (75-90% of infections)

Mortality 25%
 Only
50% surviving attain pre-infection level of function
Prosthetic Joint Infections
34

Infection rate
Knee 0.8-1.9%
 Hip 0.3-1.7%



Extremely costly
Clinical Features




Depend on timing
Early (< 3 months)
Intermediate (3-24 months)
Late (>24 months)
Prosthetic Joint Infections
35
Del Pozo JL, N Engl J Med 2009; 361(8):787-794
Risk Factors for Prosthetic Joint Infections
36
Early Infection
Late Infection
Signs of Infection
Prolonged duration of surgery
Type of prosthesis
Slow recovery
Number of OR personnel
RA
Wound infection
Inexperienced primary
surgeon
Nonarticular infections
UTI
Advanced age
Duration of implant(?)
Failed fracture
RA
Loosening of implant (?) Increased pain
Periop nonarticular infections
Decreased ROM
Diabetes
• Revision arthroplasty has a 5-10x increased risk!
From UpToDate®. Adapted from Wymenga, et al., Acta Orthop Scand 1992; 63:665,
and from Blackburn, WD Jr, Alarcon, GS, Arthritis Rheum 1991; 34:110.
Pathogenesis of Prosthetic Joint Infections
37



Wound contamination
Hematogenous seeding
Microbiology
Early infections typically due to S. epidermidis
 Late infections (hematogenous) due to S. aureus > others


Mucoid biofilm
Coalesced glycocalyx forms on prosthetic joint
 Protective environment from host defenses, antimicrobials

Diagnosis
38







Joint fluid analysis is key
Leukocytosis (<10%)
Fever (<50%)
Elevated ESR/CRP
Cultures or tissue biopsy
Radiographs
Scintigraphy


Gallium or technetium scans
DDx includes aseptic joint loosening
Treatment of Infected Prosthetic Joints
39






Surgical removal of hardware
 > 90% of prosthesis have to be removed
Arthrodesis
Antibiotics
 5-6 weeks of IV antibiotics
 Rifampin used in conjunction with other antibiotics
Delayed implantation with antibiotic impregnated cement
Reinfection rate 10% at 3 yrs, 26% at 10 yrs
Mortality 5-20%
40
Prevention of Septic Arthritis
41

Antibiotic prophylaxis for dental procedures in patients who
have undergone total joint replacements
Within 2 years of implant
 Immunocompromised patients
 Patients with certain comorbidities


Controversial with no supporting studies; only consensus
statements (2003)

Risk of late infection low
10-100 cases per 100,000 patients per year
 Counsel your patients

Prevention of Septic Arthritis
42
J Am Dent Assoc 2003; 134(7):895-899
Prevention of Septic Arthritis
43
J Am Dent Assoc 2003; 134(7):895-899
Summary
44



Septic arthritis is the most potentially dangerous and
destructive forms of arthritis
Risk factors include age > 80, DM, RA, prosthetic
joints, recent joint surgery, and skin infection
Most common etiologic microorganism is S. aureus
 Don’t



forget CA-MRSA, HA-MRSA!
Cornerstone of diagnosis is arthrocentesis
Key to better prognosis is to treat ASAP
Significant morbidity and mortality
From UpToDate®. Adapted from Wymenga, et al., Acta Orthop Scand 1992; 63:665,
and from Blackburn, WD Jr, Alarcon, GS, Arthritis Rheum 1991; 34:110.
Special Cases
45
Septic Arthritis in Children
46



>90% monoarticular
Knee and hip in 2/3 of cases
Children <2 years old more susceptible
Signs of joint disease in neonate/infant minimal/absent
 S. aureus > Grp B strep, Gram negatives



Decline in H. flu septic arthritis in kids < 5
Septic arthritis often secondary to adjacent osteomyelitis
Metaphyseal and epiphyseal blood vessels communicate
 Some long bone metaphyses are within joint capsule

Septic Arthritis in Children
47

Age very helpful in determining likely organism
Age
Microorganism
Neonates
Staphylococcus aureus (hospital-acquired)
Streptococci (community-acquired)
Gram-negative bacilli
Age < 2 years
Haemophilus influenzae (less common with immunizations)
Staphylococcus aureus
Age 2-15 years Staphylococcus aureus
Streptococcus pyogenes
Gilliland, WR. Rheumatology Secrets, 2nd ed, ed. West 2002. Hanley & Belfus: Philadelpha, pp. 281-289
Septic Arthritis (SA) in Children
48



AVN of femoral head can complicate SA of the hip
Outcome more favorable than in adults
Long-term sequelae occur in 25% of cases
 Leg
length discreptancy
 Limitation of joint mobility
 Secondary degenerative joint disease
IVDA and Septic Arthritis
49


Clinical signs and symptoms may be subtle
Common sites – axial skeleton
Sternoclavicular joint
 Sternomanubrial joint
 Lumbar vertebrae
 SI joint, symphysis pubis


Organisms
Staphylococcus aureus
 Staphylococcal epidermidis
 GNRs (Pseudomonas, Serratia)
 Candida spp.


Good prognosis if given proper therapy unless HIV +
More Special Populations
50
Underlying Disorder
Microorganisms
Alcoholism/cirrhosis
Gram negative bacilli, Streptococcus pneumoniae
Malignancies
Gram negative bacilli
Diabetes mellitus
Gram negative bacilli, Gram-positive cocci
Dog/cat bites
Pasteurella multocida
Hemoglobinopathies
Streptococcus pneumoniae, Salmonella spp
Raw milk/dairy products
Brucella spp
SLE
Encapsulated organisms (Neisseria, Salmonella, Proteus)
Gilliland, WR. Rheumatology Secrets, 2nd ed, ed. West 2002. Hanley & Belfus: Philadelpha, pp. 281-289
Septic Bursitis
51
UpToDate® (above)
Hochberg. Figure 96.4. (left)
Septic Bursitis
52

Superficial bursae more susceptible to infection
 Olecranon

bursa, prepatellar bursa (“housemaid’s knee”)
Etiology is direct extension of superficial infection
 Extensive cellulitis
surrounding bursa (>50%)
 Look for skin lesions which are portal of entry
 Can also see distal edema of affected limb

Cause typically due to trauma to superficial bursae
 Carpet
laying, mining, plumbing, roofing, gardening,
wrestling, gymnastics, hemodialysis
Septic Bursitis Management
53

Aspirate effusion/fluctuance
 Fluid
usually inflammatory
 WBC
elevated but not as much as septic joints
 Use
large bore needle if fluid thick
 Gram stain usually positive for gram positive cocci

Start bactericidal anti-staphylococcal agent
 S.
aureus responsible for >80% of cases
Septic Bursitis Management
54

Mild infection
 Oral
agent
 Outpatient follow-up and adequate drainage

Severe infection
 Admission
and serial aspirations
 Parental antibiotics
 Oral abx after control of infection for additonal 1-3 wks


Surgical drainage or bursectomy rarely necessary
Prognosis excellent
Mycobacterium Infections
55

Tuberculosis
 Osteoarticular
involvement in 1-5%
 Infection via hematogenous spread
 Types of articular infections
 Spinal
tuberculosis
 Peripheral joints
 Reactive
Pott’s Disease
56




Tuberculous spondylitis
Most common form of osteoarticular infection
Thoracic > lumbar > cervical > sacral
Collapse of anterior vertebral body
 Gibbus

deformity
May extend
 Adjoining
discs, vertebrae, distant sites
 Paravertebral or psoas abscesses
57
Above: Gibbus deformity
Left: Paravertebral abscess
Tuberculosis Joint Infections
58

Peripheral arthritis

Monoarticular (hips, knees)

 Insidious, limited inflammation

 Phemister’s triad

 Juxta-articular osteopenia
 Marginal erosions
 Gradual narrowing of joint space

SF WBC increased
AFB smears (20% +)
Cultures (80% +)
Diagnosis best made by
synovium biopsy
Mycobacterium Infections
59

Reactive Arthritis
 AKA
Poncet’s disease
 Polyarticular arthritis in
setting of active TB
 Hands and feet
 SF, synovium sterile
 Resolves with TB
treatment

Others
 BCG
vaccine
 May
cause a reactive
arthritis as well
 Atypical
mycobacteria
 M. marinum
 M. kansasii
 M. avium
 M.
leprae
complex
Fungal Infections
60


Candida

 Rare

 C.
albicans

Coccidiomycosis

 Primary

 Disseminated

 Polyarticular
 Migratory
 Chronic
knee
monoarthritis

Sporotrichosis
Blastomycosis
Cryptococcosis
Histoplasmosis
Actinomyces
Aspergillus
 May mimic Pott’s dz
Parasites

Giardia, entamoeba,
trichomona, toxoplasma
Questions?
61