Fungal osteomylitis and septic arthritis

FUNGAL OSTEOMYLITIS AND SEPTIC ARTHRITIS

Dr. Giridhar Boyapati

PG

Dept. of Orthopedics

More than 150 species are pathogenic to man.

Most common offending organisms are CANDIDA and ASPERGILLUS.

Others : HISTOPLASMA

BLASTOMYCES

COCCIDIOIDES

CRYPTOCOCCUS

SPOROTHRIX

RISK FACTORS FOR INFECTION

Immunosuppression by disease or medication

Substance abuse

Presence of an indwelling catheter

Parenteral hyperalimentation

Diabetes mellitus

Use of broad spectrum antibiotics

HIV

Organ transplantation

ROUTES OF SPREAD

Hematogenous spread from lungs

ex Candida

Blastomycosis

Coccidiodies

Histoplasma

Cryptococcus

• Contiguous infection spread

Direct inoculation during

implantation of prosthesis

instrumentation

arthrocentesis

intraarticular steroid injections

open fractures

ex Aspergillus, Sporothrix, Eumycetoma sps

Symptoms assosiated with direct direct innoculation of fungal pathogen typically appear within 4 weeks of inoculation.

Candida albicans and candida parapsilosis form biofilms that are commonly associated with antifungal resistance.

CANDIDA SPECIES

Candida albicans

C. tropicalis

C. glabrata

C. parapsilosis

Non-albicans Candida species have increased progressively as emerging causes of Candida osteomyelitis

Staphylococcus aureus and other bacteria may be identified in mixed cultures

Most common fungal pathogen causing septic arthritis and osteomyelitis

Normal human flora

Two types of clinical presentations

2/3 patients > acute infection

1/3 patients > indolent course with mild artritis

• Hematogenous spread in 70%

• Positive blood cultures in 30-50%

Mostly effect vertebrae, sternum,ribs, femur, hip, fascial bones, humerus, foot, ankle, tibia.

Candida osteomyelities of spine-- Xray

vertebral end plate destruction

disc space narrowing

demineralization

mottled trabecular bone pattern

Grows in routine medium

Candida metabolites d-arabinitol and β-d glucan are markers of peri-prosthetic infection

Drugs :

Fluconazole 400mg for 6-12 months for OM

6 weeks for septic arthritis

Liposomal AMB for 2 weeks followed by fluconazole

for 6-12 months for OM and 6 weeks for seprtic

arthritis.

Echinocandins or AMB for 6 weeks followed by fluconazole

ASPERGILLUS

A. fumigatus

A. flavus

A. niger

A. terreus

Present in soil and dust

Commonly cause focal infections in he lung aspergilloma

In children contiguous spread from a pulmonary or sinus infection or from overlying skin

In adults hematogenous spread, mostly effecting lumbar spine.

Typically septic arthritis is the result of hematogenous spread from adjacent infected bone

Septic arthritis patient presents with fever, chills, malaise painfull swollen joints.

Spl tests : Grocott-Gomori-Methenamine silver(GMS) stain and fungal medium are required

Drugs Voriconazole iv or oral

Liposomal AMB

Capsofungin

Posaconazole

Itraconazole

COCCIDIODES

Soil borne dimorphic fungi endemic to south western US, mexico, south america

C. immitis

C. posadasii

In case of respiratory infections 0.5 – 1% have extrapulmonary involvement

In case of hematogenous infection 20% risk of developing bone and joint involvement

Septic arthritis charecterized by synovial proliferation rather than accumulation of synovial fluid.

Spl test: serum coccidiodes complement fixation titers is elevated

Drugs : Fluconazole

Itraconazole

Ketoconazole

AMB

HISTOPLASMA

Dimorphic fungi

H. capsulatum

H. duboisii

Also present in birds and bats excreta

Primary respiratory infection causes a influenza like illness

Spread to regional lymph nodes leading to granulomatous inflammatory reaction necrosis and calcification.

<0.1 % of infections cause migratory polyarthritic syndrome

Septic arthritis is rare and typically involves the knee

Associated with immune complex arthritis characterized by synovial proliferation

Osteomylitis presents with cortical periosteal thickening, widened medullary canal, osteopenia

Treatment

Mild : Itraconazole 200mg tid for 3days then 200mg bd for 6-12 weeks.

Moderate to severe : Liposomal AMB for 1-2 weeks followed by Itraconazole

BLASTOMYCES DERMATITIDIS

A dimorphic fungus

Causes Blastomycosis or Gilchrist disease

Causes a acute respiratory infection

Extra-pulmonary manifestations occur in 25-40% of patients

Disseminated infection in transplant recipients and HIV pts

Special tests : wet mount microscopy, GMS stain

Drugs :

AMB 0.7-1mg/kg/d for 1-2 weeks then Itraconazole 200mg tid for 3 d and 200mg bd for 12 months

Liposomal AMB for 1-2 weeks then Itraconazole

Only Itraconazole for mild to moderate disease.

CRYPTOCOCCUS

Infection by inhalation or direct innoculation

Spl tests: serum cryptococcal antigen

GMS, PAS stains

Management

No meningoencephalitis: Fluconazole 400mg/d for -12 months

meningoencephalitis : AMB + Flucytosine

Liposomal AMB

MANAGEMENT

SURGICAL MANAGEMENT

Debridement includes removal of sinus tracts, necrotic bone and soft tissue, placement of antibiotic or antifungal beads.

Hardware needs to be removed

Surgical debridement in spinal infections is more extensive and may require stabilisation in case of instability.

PHARMACOLOGICAL AGENTS

AMPHOTERICIN B: a macrolide antifungal drug that binds to ergosterol in fungal cell wall.

Side effects: renal toxicity, febrile reactions, anemia, infusion reactions

Dose : 0.5-1 mg/kg/d I.V

Liposomal AMB : 1-5 mg/kg/d I.V

less renal toxicity and febrile reactions than AMB

ANTIFUNGAL TRIAZOLES : synthetic compounds that inhibit ergosterol synthesis through inhibition of cytochrome P450 dependent enzymes.

Fluconazole : poor activity against aspergillus

Voriconazole : good CNS penetration and affective aginst fungi resistant to fluconazole. Cause transient visual blurring.

Itraconazole

Posaconazole

ECHINOCANDINS : inhibition of 1,3 β glucan

Capsofungin

Micafungin

Anidulafungin

Effective against biofilms

FLUCYTOSINE : pyrimidine analogue and thymidylate synthesis inhibitor.

Used in combination with other antifungals

For severe candida and cryptococcus infections

PROSTHETIC JOINT INFECTION

Only < 1% of PJI are fungal

Most common pathogen is Candida species

Symptoms pain ,erythema, effusion, fistula formation.

Elevated ESR and CRP, positive joint aspirate cultures.

Cultures in Sabourads dextrose agar.

Non surgical management

Who can not tolerate explantation and placement of cement spacers.

Require atleast 1 year of antifungal treatment and life long supressive therapy.

Echinicandins are usefull in these cases as they can penetrate biofilms.

Surgical

Two stage revision procedure

Debridement, delayed reimplanatation and antifungal medication.

Time of reimplanatation is longer in THR than in TKR.

Fungal infections require long reimplanatation intervels then bacterial infections.

Temporary spacer static or dynamic with or without cement is used

Antibiotic loaded spacers have vancomycin 4g, tobramycin 4.8g and AMB 50mg in 40g bone cement.

The elution of most of antifungals is worse than that of antibacterial agents.

Systemic antifungal drugs are administered for 6weeks.

Reimplantation

Surgical wound is healthy

Normal CRP

Patient is stable

Correction of nutritional status

Reaspiration cultures negative

High failure rate of revision in fungal infections than in bacterial.

Candida Osteomyelitis:Analysis of 207 Pediatric

and Adult Cases (1970–2011)

Maria N. Gamaletsou, Dimitrios P. Kontoyiannis,

Clinical Infectious Diseases 2012;55(10):1338–51

Demographic Characteristics and Underlying Conditions

age was 30 years with a predominance of males .

The majority of patients were not heavily immunosuppressed (ie, underlying hematology malignancy, transplantation, or solid tumor).

Only a minority of patients (10%) had trauma or open wounds

Candidemia and Osteomyelitis

Candida osteomyelitis was the first proven Candida site involvement in 50% of patients

The remaining half of patients initially had candidemia or other form of candidiasis.

15% had concomitant candidemia at the time of diagnosis of Candida osteomyelitis

Osteoarticular Distribution

Majority of patients had 2 or more sites of infection.

Most commonly effect the vertebrae, femur, ribs, sternum, and humerus .

Intervertebral discs were infected in 40% patients, costochondral, costosternal, and costoclavicular joints in 11% and synovial joints in 21%

The most common synovial joints infected were knee (11%) and hip (5%).

Effect of age

Vertebrae were the most commonly infected bone sites in adults whereas femur were most common in pediatrics

The most common distribution of infected sites for adults was vertebrae, ribs, and sternum. For pediatric patients , femur, humerus, and vertebra/ribs.

Irrespective of age, local symptoms were usually present, and overall outcome was similar.

TREATMNT AND OUTCOME

44% patients were treated with antifungal agents only,

5% underwent surgical treatment only, and

48% were treated with both antifungal therapy and surgery

Debridement was the most common surgical procedure followed by drainage, bone grafting, stabilization, decompression, and intervertebral fusion.

Median duration of therapy was 90 days (range, 7–720 days).

There was no apparent benefit on outcome of any particular antifungal agent.

EFFECT OF HARDWARE

27% achieved complete response

64% partial response;

45% relapsed

EFFECT OF BACTERIAL INFECTION

In patients having concurrent bacterial infection.

33% had complete response

53% had partial response,

37% relapsed

Thank you

Fungal infections of the spine. Report of eleven patients with

long-term follow-up.

Frazier DD, Campbell DR

J Bone Joint Surg Am 2001 Apr;83-A(4):560-5

• for 10 of the 11 patients, the average delay in the diagnosis was ninety-nine days;

• 9 patients were immunocompromised secondary to diabetes mellitus, corticosteroid use, chemotherapy for a tumor, or malnutrition;

• sources of the spinal infections included direct implantation from trauma (one patient), hematogenous spread (four patients), and local extension (two patients);

• infection followed elective spine surgery in three patients, and the cause was unknown in one

paralysis secondary to the spine infection developed in eight patients;

10 patients were treated with surgical débridement;

all eleven patients were treated with systemic antifungal medications for a minimum of six weeks;

after an average of 6.3 years of follow-up, the infection had resolved in all nine surviving patients