BONE AND JOINT

INFECTION

Cucunawangsih

MSC/6 Sept 2011

Table of arthralgia and arthrititis in infectious diseases
Infectious agent
Viral arthritis
Hepatitis B
Rubella
Mumps
Ross river and other togaviruses
Parvovirus
Reactive arthritis
Campylobacter, Yersinia,
Salmonella, Shigella, Chlamydia
trachomatis (Reiters syndrome)
Septic arthritis
Staphylococcus aureus
Streptococcus (Group A and B)
Haemophilus influenzae
Neisseria gonorrhoeae
Mycobacterium tuberculosis
Borrelia burgdorferi
Gram-negative bacilli
Sporothrix schenckii
Comments
Occurs in prodromal period; due to circulating immune complexes
Especially in young women, often follows live virus vaccine
Unusual; mostly in men
Mosquito-transmitted infections in Australia (Ross River) and Africa
May follow adult infection
Post-infectious arthritis, HLA B27-associated, no bacterial
invasion of joint, immune mediated
Commonest cause of suppurative arthritis
Common in adults and children
Occurrence in children has decreased with H.influenzae vaccine
May affect multiple joints
Often with bone lesions, especially weight bearing joints and bones
Arthritis ( a late feature of Lyme disease)
Neonatus, the elderly, patients with immune deficiency disorder
Fungal infection of joints, increased risk with HIV infection
 INFECTIOUS ARTHRITIS OF NATIVE JOINTS

INTRODUCTION
Acute bacterial arthritis
(suppurative, pyogenic, or septic arthritis)
Nongonococcal arthritis
Gonococcal arthritis

Viral arthritis
Infectious arthritis
Chronic infectious arthritis
Fungal arthritis
Mycobacterial arthritis

Septic bursitis
 ACUTE BACTERIAL ARTHRITIS
Predisposing factors
Joint disease
Rheumatoid arthritis, crystal-induced arthritis

Osteoarthritis

TRANSMISSION Chronic systemic disease

Hematogenous Diabetes mellitus, renal failure,

Direct collagen vascular disease

Bacteria inoculation into joint
through surgery, trauma,
percutaneous puncture
Contagious spread
Malignancy, sickle cell disease
Immunosuppression
HIV infection, immunosuppressant therapy
including systemic steroid
Organ and bone marrow transplantation

Hypogammaglobulinemia

Trauma
Prosthetic joint
IV drug use
Endocarditis
 NONGONOCOCCAL ARTHRITIS
PATHOPHYSIOLOGY
Complex
Adherence of bacterial and colonization to synovial membrane
e.g., S.aureus has surface receptors
Fibronectine-binding protein
Microbial surface components recognizing adhesive
matrix molecules (MSCRAMMs)

Bacterial proliferation

Bacterial product/toxins

Immune response
NONGONOCOCCAL ARTHRITIS
Etiologic agent
Gram-positive
Staphylococcus aureus (37-65% of cases, adult)
Staphylococci coagulase negative
Streptococci
Streptococcus pyogenes
Streptococcus pneumoniae
Streptococcus agalactie
Gram-negative
Escherichia coli
Haemophillus influenzae (young child)
Neisseria gonorrhoeae
Neisseria meningitidis
Pseudomonas aeruginosa
Salmonella spp.
Anaerobic bacteria
 NONGONOCOCCAL ARTHRITIS
Clinical and epidemiological associated with selected bacteria causes of
septic arthritis
Clinical or epidemiologic feature
Rheumatoid arthritis
IV dug use
Diabetes, malignancy
Immunocompromised host
Neonates, child < 2 years
Young adult, female
Fibrocartilaginous joints
Cat/dog bite
Human bite
Post partum women
Status after reconstructive surgery
Etiologic agent
Staphylococcus aureus
S.aureus, P.aeruginosa
S.aureus, group B streptococci
S.aureus, streptococci, enteric gram-negative
bacilli
Gram-negative bacilli, Kingella kingae
Neisseria gonorrhoeae
S.aureus, P.aeruginosa
Pasteurella multocida, anaerobe bacteria
Oral flora
Mycoplasma hominis
Clostridium sp.
 GONOCOCCAL ARTHRITIS

Neisseria gonorrhoeae
o Incidence: 3-7,5% of cases
(women 4x than men)
o Sexually active persons
o Disseminated gonococcal infection (DGI)
Tenosynovitis
Dermatitis
Polyarthralgia
without purulent joint infection

GO complication
 GONOCOCCAL ARTHRITIS

Adolescent with septic arthritis of left ankle

with petechial and necrotic skin lesions on
the feet. Blood cultures were positive for
Neisseria gonorrhoeae.

Usually only 1 or 2 joints are involved,

primarily the knees, ankles, wrists, and elbows

Onset is often acute, with fever, severe pain, and limitation of

movement but may occur without constitutional symptoms

Infected joints are swollen, and skin may be warm and red.
 ACUTE BACTERIAL ARTHRITIS

LABORATORY DIAGNOSIS

Blood culture
10-50% are positive
Synovial fluid
WBC > 50.000/mm3
Gram stain - 1/3 positive
Culture - 25-80% are positive
Causative agent identified in 2/3 of cases
 ACUTE BACTERIAL ARTHRITIS

TREATMENT
Recommended empirical therapy for adult native joint bacterial arthritis
Gram stain Antimicrobial*
Gram-positive cocci
No risk for MRSA~ Nafcilin/oxacilin 2 g q4h or cefazolin 2g q8h or
Penicillin/cephalosporin allergic: clindamycin 900 mg q8h or vancomycin 1 gq12h
Risk for MRSA~ Vancomycin 1g q12h
Gram-negative cocci Cefriaxone 1g q24h

Gram-negative rods Ceftazidime or cefepime 2 g q8h or piperacilin-tazobactam 4.5 g q6h or carbapenem

Gram stain negative
(imipenem 500 mg q6h or meropenem 1g q8h)
Penicillin/cephalosporin allergic: aztreonam 2g q8h or ciprofloxacin 400 mg IV q12h or
levofloxacin 750 mg q24h
Regimen for gram-positive cocci plus
Ceftazidime or fluoroquinolone (ciprofloxacin or levofloxacin) or aminoglicoside
(tobramycin or gentamicin)

*All indicated dosage are IV for patient with normal renal function
~Risk facrtor for MRSA include previous infection or colonization with MRSA, chronic renal failure or
Debilitating illness, and frequent or prolonged hospitalization
 VIRAL ARTHRITIS

Arthritis or arthropathy caused by viral agent is often acute,

occurs concurrently with sign and symptoms of febrile systemic illness,
and resolves along with other manifestations of illness

Directly by infecting synovial

Indirectly through host immune-mediated responses

Pathogenesis is poorly understood

Human parvovirus B19 (HPV-B19)
Hepatitis B (during febrile prodome)
HIV, Human T-cell lymphotropic virus type-1 (HTLV-1)
Chikungunya, Onyong-nyong, Mumps
etc
 MYCOBACTERIAL ARTHRITIS

10-11% of extrapumonary tuberculosis

Risk factor
Sosioeconomic class
Incarceration
Alcohol abuse
IV drug use
Immunosuppresive drug therapy
HIV infection
Preexisting joint disease
Incidence higher and increasing
Escalating prevalence of HIV disease
 MYCOBACTERIAL ARTHRITIS
Hematogenous dissemination
associated with primary pulmonary TB

Granulomatous monoarthritis

Knee, hip, ankle

Laboratory diagnosis
Synovial fluid
Leukocyte count 10,000 20,000 cells/mm
Acid fast bacilli positive
Culture 80% positive
 SEPTIC BURSITIS
Common
Trauma or accidental percutaneous puncture
(rarely from intrabursal injection of corticosteroid)

Subcutaneous olecranon or prepatellar bursae

Painfull swelling
Redness
Increased warmth of affected bursae

Staphylococcus aureus
Streptococcus sp.
Gram-negative bacteria
Mycobacteria spp.
Fungi
 OSTEOMYELITIS

DEFINITION
Infectious process involving the various components of bone
characterized by progressive inflammatory destruction of bone,
necrosis and new bone formation

ACUTE OSTEOMYELITIS
CHRONIC OSTEOMYELITIS

Mechanisms of Infection
Hematogenous spread
Contagious spread
In association with vascular insufficiency
 OSTEOMYELITIS

Etiologic agents of osteomyelitis

Common ( >50% of cases)
Staphylococcus aureus

Coagulase-negative staphylococci

Occasionally ( >25% of cases)

Streptococci, enterococci, Pseudomonas spp., Enterobacter spp. Proteus spp.,
Escherichia coli, anaerobes
Rarely ( <5% of cases)
M.tuberculosis, fungi, Mycoplasma spp., Salmonella spp.

Normally bone is highly resistant to infection

Bone trauma/presence of foreign bodies
Bacterial inoculation with large inocula
Infection
 OSTEOMYELITIS - Staphylococcus

Free-living Bacteria

Gram-positive Gram-negative

Cocci

Staphylococcus S. aureus
S. epidermidis
S. sapropiticus
Streptococcus
 OSTEOMYELITIS - Staphylococcus

Enzymes:
Coagulase
Catalase
Hyaluronidase
Fibrinolysin

Cell wall virulence factors:

Protein A
Bind to Fc moiety of IgG, exerting an antiphagocytic effect
Fibronectin-binding protein (FnBP)
Promote binding to mucosal cells and tissue matrices
Cytolytic exotoxins:
, , toxins
Attack mammalian cell (including red blood cell) membranes and are often referred to
as hemolysin
OSTEOMYELITIS - Staphylococcus
 OSTEOMYELITIS

Sign and symptom

Nonspecific pain
Fever-chill
Local swelling
Erythema in the proximity of the involve bone are seldom seen

Diagnosis
First suspected on clinical ground
Confirmation with radiologic, microbiology, and pathologic test
Identification of causative agents is crucial

In vitro susceptibility data

Help optimize medical

 OSTEOMYELITIS

Acute hematogenous osteomyelitis

Characterized by the abrupt onset of localized pain and tenderness at a single
site, fever, and increased inflammatory marker (ESR, C-reactive protein)
Initial empirical antibiotic therapy should be directed at Gram-positive cocci,
including MRSA

Osteomyelitis Secondary
Contagious, occur after trauma, orthopedic surgery
Common symptoms: pain, tenderness, erythema, and drainage at the site of
injury or surgery
Often polymicrobial
Sampel for culture is pus and deep tissue/bone sample
treatment is for least 4 weeks, IV, and the antibiotic chosen is depend on the
result of culture organism and their susceptible
 OSTEOMYELITIS

Osteomyelitis associated with vascular insufficiency

Often occur in patient with DM
Neuropathy and impaired blood flow leads to the development of chronic lower
extremity cellulitis and underlying osteomyelitis
Multiple Gram (+), Gram (-) aerobic, anaerobic
Treatment:
Initial tx include vancomycin, antipseudomonal beta-lactam
Devinitive tx based on the result of culture susceptibility
Duration is 6 weeks
 OSTEOMYELITIS

Chronic osteomyelitis
Characterized by a draining sinus tract from bone to skin
Occur years later at site of previous bone infection
Often polymicrobial, and the same organism (especially S. aureus)
Treatment:
Surgery debridement
Devinitive tx based on the result of culture susceptibility
High dose IV
Duration is 6 weeks
 OSTEOMYELITIS

Microorganisms First choice~ Alternative choice~

Staphylococci
Oxacillin sensitive Nafcillin/oxacillin Vancomycin
Oxacillin resistant (MRSA) Vancomycin Linezolid or

Penicillin-sensitive streptococci Penicillin G Levofloxacin plus

rifampin
Enterococci, streptococci Penicillin G Vancomycin

/ampicillin/gentamicin Vancomycin

Enterobacteriaceae Ceftriaxone/ceftazidime/ Ciprofloxacin*

Enterobacter sp. or meropenem
Pseudomonas aeruginosa

~Antimicrobial selection should be based on in vitro sensitivity data

*Should be avoided if possible in pediatric patients and in osteomyelitis associated
with fracture
 INFECTION WITH PROTHESES IN BONE AND JOINS

1-5% of indwelling prostheses become infected

Locally introduced
Hematogenous
Infection develop at bone-cement interface

Microbial agents Symptoms

Coagulase-negative staphylococci Joint paint
Fever
Staphylococcus aureus Periarticular swelling
, Hemolytic staphylococci Wound/cutaneous
Enterococci sinus drainage
Gram-negative aerobic bacilli
Obligate anaerobes
 INFECTION WITH PROTHESES IN BONE AND JOINS

PREVENTION
Evaluate the presence of might predispose to infection/bacteriemia
Perioperative antibiotic prophylaxis

Oxacillin or cefazolin
Immediately before operation and for 1-2 days thereafter

Use of aminoglycoside-impregnated cement during implantation

Filtered laminar airflow system

Exhaust-ventilated suits
 ANTIMICROBIAL PROPHYLAXIS FOR SURGICAL PROCEDURES

1. RISK FACTOR FOR INFECTION

Surgical antibiotic prophylaxis is indicate for patients at high risk of
infection or complication from postoperative infection
Classification Criteria Infection Rate
No acute inflammation or entry into GI, respiratory, GU, or bialry
Clean >5
tract; no berak in aseptic technique occurs; wound primarily closed
Elective, controlled opening of GI/resp/GU/biliary tract without
Clean-contaminated significant spillage; clean wound with major break in sterile > 10
technique
Penetrating trauma (> 4 hours); major technique or major spillage
Contaminated 15 - 20
from GI; acute, non purulent inflammation

Penetrating trauma (> 4 hours); purulent or abscess (active

Dirty 30 -40
infectious process); postoperative perforation of viscera

Current recommendation: clean surgeries involving implantation of

prosthetic material; clean contaminated; and select contaminated wound
 ANTIMICROBIAL PROPHYLAXIS FOR SURGICAL PROCEDURES

2. Decision of surgical antimicrobial prophylaxis

The choice of agent is based on:
a. The most likely pathogen associated with surgical site infection that
may occur
b. Spectrum of activity of the agent
c. Pharmocokinetic characteristic half-life, adverse event profile,
impact bacterial resistance, and cost
Antibiotic Regimen and Adult Dose
Procedur Predominant Organism(s)
(alternative)
Clean
Orthopedic ((Total joint
replacement, internal fixation of S. aureus, S. epidermidis Cefazolin 1 - 2 gr; vancomycin 1 gr
fracture
Clean contaminated
Head and neck (involving incision Cefazolin 2 gr; 600 mg clindamycin
S. aureus, oral anaerob, streptococci
through mucosa) - 1.5 mg/kg gentamycin
 ANTIMICROBIAL PROPHYLAXIS FOR SURGICAL PROCEDURES

2. Decision of surgical antimicrobial prophylaxis

Antimicrobial with shorter half-lives may require administration of an
additional intraoperative dose in prolonged surgical case

Single dose preoperative prophylaxis is sufficient for most surgical

procedure

To maximize the benefit of prophylaxis, antibiotics should given within 1

hour before incision to achieve adequate drug level at surgical site
 ANTIMICROBIAL PROPHYLAXIS FOR SURGICAL PROCEDURES

3. Sign of surgical site infection

Typical sign: incision site wound is red, warm, and purulent and
sometime swollen, tender, or painful

Surgical site infections are classified as superficial or deep incision and

usually occur within 30 days after procedure. Deep infections can occur
up to several months after surgery and up to a year after implantation of
prosthetic material.
ANAEROBIC BACTERIA
Classification of obligate anaerobes OVERVIEW

Free living bacteria

Gram-positive Gram-negative

Rods Rods

Clostridia Bacteroides

Clostridium botulinum Bacteroides fragilis

Clostridium difficile
Clostridium perfringens
Clostridium tetani

Lippincotts Illustrated Review Microbiology 2 ed

 OVERVIEW
OBLIGATE ANAEROBE ORGANISMS

Anaerobic Metabolic
Production of energy by fermentation
Damage by free oxygen
Colonize human body
Cause disease
Genus Clostridia
soft tissue and skin infection (cellulitis, fascilitis), antibiotic-associated colitis,
and diarrhea
Exotoxin associated with tetanus etc
Genus Bacteroides
visceral and other abscesses
Generally polymicrobic infection with other bacteria
 CLOSTRIDIUM SPECIES

Anaerobic gram-positive rods

Cannot use free O2 in

energy production

Use small organic moleculs,

like pyruvate

Vegetative form are

inhibited or damage by O2

Spores are resistant to chemical disinfectants, ultraviolet irradiation

or autoclaving condition (121C for 15 at increased pressure) 1
 CLOSTRIDIUM SPECIES

Clostridia spesies are ubiquitos in nature, with its vegetative form

as part of the normal flora of vagina and gastrointestinal tract.

Its spores are found in soil

(spores are rarely seen in the body or following in vitro cultivation)

Clostridium tetani Clostridium perfringens

tetanus gas gengrene

food poisoning
Clostridium botulinum
Clostridium difficile
botulisms
Antibiotic-associated colitis
 CLOSTRIDIUM PERFRINGENS

Gram-positive rods, thick,

brick-shaped, anaerobic
Catalase-negative
Non-motile

Gram stain, x 1000

Cl. perfringens colonies on blood agar

-hemolysis, some strains produce a double zone of hymolysis

This culture has been incubated anaerobically

 CLOSTRIDIUM PERFRINGENS

Neglar Reaction
18 hours anaerobically
at 37C

Detect production of
letcithinase and opacity
in egg yolk agar (EYA)

Distinguishes C.perfingens
from other clostridia

Half of the plate (EYA) covered with C.perfringens antitoxin. This organisms are
streaked across the plate so that inoculum passes from the antitoxin-free half of
the plate to the antitoxin-covered part. After overnight anaerobic incubation, a positive
result is shown by opacity in the medium surrounding the inoculum
on the non-antitoxin half of the plate. Right side, no antitoxin.
 CLOSTRIDIUM PERFRINGENS

PATHOGENESIS
Cl.perfringens secrets a variety of exotoxin,
enterotoxin, and hydrolytic enzyme that facilitate
the disease process

Exotoxins
12
-toxin is lecithinase (phospholipase C)

Enterotoxin
Small, heat-labile protein
Act in lower small intestine

Degenerative enzyme
Protease, DNase, hyaluronidase, collagenase
 CLOSTRIDIUM PERFRINGENS

CLINICAL SIGNIFICANCE
The disease result from combination exotoxin and/or enterotoxin
and degerative enzyme

Myonecrosis (gas gangrene)

Contamination with infected soil or endogenous
transfer from the intestinal tract
Predisposing factors
Severe and open wound
(fracture/ischemia-producing injuries)

The exudate are copious and foul smelling

Toxin carried by circulation

Shock, renal failure , intravasc hemolysis

Untreated Fatal (days)
 CLOSTRIDIUM PERFRINGENS

CLINICAL SIGNIFICANCE
Anaerobic cellulitis
Infection of connective tissue

Food poisoning
Cl.perfringens is a cause of food poisoning
Nausea, abdominal cramp, and diarrhea occurs 8-18 hours after eating
contaminated food

Enteritis necroticans
A necrotizing bowel disease with high mortality (>50%)

Clostridial endometritis
Gangrenous infection of uterine tissue followed by toxemia and
bacteriemia
 CLOSTRIDIUM PERFRINGENS

CLINICAL SIGNIFICANCE

Increasing pain at the site of prior injury or surgery, together

with
sign of systemic toxicity and gas in the soft tissue,
support the diagnosis of gas gangrene
Specimen collection from clinical material
Diseased tissue (biopsi)
Food and fecess patient food poisoning
 CLOSTRIDIUM PERFRINGENS

TREATMENT AND PREVENTION

IMMEDIATELY

Remove the foreign material and devitalized tissue

Debridement
Amputation

Exposure wound to O2
Hyperbaric oxygen therapi

Administration of antibiotic in high dose

Penicillin or broad-spectrum antibiotic
 SPECIMEN COLLECTION

PURULEN WOUND/ULCER
WAKTU: setiap saat, sebelum pemberian AB

METODE:
Bersihkan luka dengan NaCl 0,9% (3x)

masukkan SWAB ke dalam luka/ulcus sampai menyentuh

dinding tanpa menyentuh bag tepi atas luka/ulcus
lakukan 2x

MEDIUM TRANSPORT OBYEK GLASS

(KULTUR) (MIKROSKOPIS)
three swab transport systems (Starplex StarSwab II,
Copan VI-Pak Amies agar gel and transport swabs,
and BBL Port-A-Cul)

SEGERA KIRIM, bila tidak dapat SIMPAN PADA SUHU 4C

 SPECIMEN COLLECTION

Pyogenic arthritis in infancy and childhood. Aspirating pus from the hip joint with the needle introduced
laterally and pointed medially and upwards (A, B); aspirating pus from the knee joint with the needle
inserted from the side at the level of the lower pole of the patella (C), or at the level of the upper pole of the
patella (for effusion mainly in the suprapatellar bursa) (D); aspirating pus from the elbow joint by introducing
the needle posterolaterally just above the head of the radius; the bony landmark is shown (E).
SPECIMEN COLLECTION
TERIMAKASIH