Osteomyelitis, OM

Notes

## Basic introduction

  • This is an infection of bones that is characterized by progressive inflammatory destruction and apposition of new bone.
  • Classification of OM is based on duration of infection (acute, subacute and chronic), mechanism of infection (exogenous or hematogenous), and type of host response to the infection (pyogenic or non-pyogenic).
  • Acute hematogenous OM is the most common type of bone infections and it is more common in children and males. It is caused by the blood borne organisms.
  • In children, acute hematogenous OM mostly involves the metaphyses of rapidly growing long boneOs
  • In children below 2yrs with acute hematogenous OM, blood vessels cross the physis, hence epiphysis may as well be involved. This may lead to the shortening of a limb or angular deformity, among other effects

## Causes

  • aureus is the most common causative agent of OM.
  • Other micro-organisms that can cause OM include: Enterobacter species, group A and B Streptococcus species, fungi and mycobacteria (that can cause hematogenous OM, mainly in vertebrae, especially in immunocompromised patients)
  • In sickle-cell disease, OM may be caused by Salmonella
  • Infections can spread from an open localized wound to the bones

## Pathophysiology

  • Bacteria produce biofilm that consists of extracellular polymeric substance or exopolysaccharide that covers necrotic bone. This biofilm makes it hard for antibiotics to penetrate the affected tissue.
  • OM may occlude local blood vessels and leads to bone necrosis as well as local spread of infection
  • The infection may spread through the bone tissue and ultimately spreads to subcutaneous tissues and cause abscesses that may drain through the skin.
  • Inadequate or unsuccessful treatment of acute OM may result in low-grade chronic OM

## Risk factors

  • Surgery
  • Trauma
  • Diabetes or other systemic diseases
  • Vascular disorders (such as ischemia)
  • Peripheral neuropathy
  • Malnutrition
  • Immunocompromised cases
  • Foreign bodies (such as prosthetics)
  • Damage by radiation therapy
  • Pressure ulcers
  • Gum infection (that can easily spread to the skull)
  • Tooth infection (that can as well spread to the skull)

## Statistics

  • Recurrence rate of chronic OM in adults (even after treatment) is 10-30%d
  • The prevalence of OM in the general population of Kenya was about 1:1000f
  • In Gambia, OM accountS for 7.8% of pediatric surgical admissions and 15.4% of inpatient's daysc
  • The prevalence of malignancy arising from chronic OM is 0.2-1.6%
  • Cases of chronic OM reported in Kenyatta National Hospital from 2008 to 2012 were 2008 (108), 2009 (79), 2010 (99), 2011(79) and 2012 (53)
  • In children presenting with haematogenous OM in Kenyatta National Hospital, the commonest isolated organism is aureus accounting for 60.4% of the cases with 60% of these being MRSA strainsb

## Complications of OM

  • Amputation
  • Malignant transformation

Persistence or extension of infection

Symptoms
  • Pain
  • Fever
  • Weight loss
  • Fatigue
  • Erythema
  • Tenderness
  • Edema and /or swelling at the affected area
  • Paravertebral muscle spasm and back pain (in case of vertebral OM)
  • Radicular pain, weakness of extremity and numbness (due to compression of the spinal cord or nerve roots)
Diagnosis
  • Imaging

_X-ray

_CT Scan

_MRI (especially when soft tissues are affected)

_Bone Scan

  • ESR (elevated in both acute and chronic OM)
  • WBC Count (elevated in case of acute OM but it is usually normal in chronic OM)
  • C-reactive protein (elevated in OM and decreases after successful treatment)
  • Culture

_Bone biopsy and culture

_Blood culture (in case of the suspected hematogenous OM)

_Sinus tract culture

Differential
  • Aseptic loosening of hardware
  • Cellulitis
  • Deep venous thrombosis
  • Fasciitis
  • Gas gangrene
  • Gout
  • Infections of the spinal
  • Juvenile idiopathic arthritis
  • Lumbar
  • Metastatic bone cancer or osteosarcoma
  • Non-infected non-union
  • Pseudogout
  • Septic arthritis
  • Sickle cell anemia
  • Transient synovitis
  • Trauma
Prevention
  • Avoiding foot trauma and ulcers in diabetes
  • Proper treatment of acute OM in order to prevent chronic OM
Reference

1. Boulton AJ, Malik RA, Arezzo JC, et al. Diabetic somatic neuropathies. Diabetes Care. 2004; 27:1458-1486.

2. Issac K Ngetich (2002) A Study of Haematogenous Osteomyelitis in Children in Kenyatta National Hospital Kenya. Nairobi : unpublished masters in medicine project, School of Medicine, University of Nairobi

3. Jones HW, Harrison JW, Bates J, Evans GA, Lubega N. Radiologic classification of chronic hematogenous osteomyelitis in children. J Pediatr Orthop 2009;29:822-7

4. Lazzarini L, Mader JT, Calhoun JH. Osteomyelitis in long bones. J Bone Joint Surg Am 2004;86-A:2305-18

5. Lewis R P, Sutter V L and Finegold S M (1978) Bone Infections Involving Anaerobic Bacteria. Baltimore pub med PMID 207946

6. Mantero E, Carbone M, Calevo MG, Boero S. Diagnosis and treatment of pediatric chronic osteomyelitis in developing countries: Prospective study of 96 patients treated in Kenya. Musculoskelet Surg 2011;95:13-8.

7. Rubin RJ, Harrington CA, Poon A, et al. The economic impact of Staphylococcus aureus infection in New York City hospitals. Emerg Infect Dis. 1999; 5:9-17.

8. Wirbel R, Hermans K. Surgical treatment of chronic osteomyelitis in children admitted from developing countries. Afr J Paediatr Surg 2014;11:297-303

9.Kenyan Ministry of Health. Clinical guidelines for management and referral of common conditions at levels 4-6. Hospitals. 2009; 3:259-261.http://apps.who.int/medicinedocs/documents/s21000en/s21000en.pdf

10. Ministry of Health, Kenya. Kenya Essential Medicine List (2016). http://publications.universalhealth2030.org/uploads/KEML-2016Final-1.pdf

Management

## General notes

  • Early diagnosis and appropriate surgical and antimicrobial treatment are key to the management of OM
  • A multi-disciplinary approach is required for effective management of OM (involving an orthopaedic surgeon, an infectious disease specialist, and a plastic surgeon)
  • OM that is associated with prosthetics (such as fixation screws, plates and artificial joints), is extremely difficult to cure without removal of the prosthetic device.
  • Antibiotics are administered for 4 - 8wks
  • Initial treatment should be with a broad-spectrum antibiotic but it should be changed according to the results of culture and sensitivity
  • The recommended antibiotics should be effective against both gram-positive and gram-negative organisms

 

## Antibiotic regimes within the Essential Drug List (EDL)

_OM due to Staphylococcus aureus:

  • IV or IM Cloxacillin 2g QID x 2/52 then Caps Cloxacillin 1g QID

OR

  • IV or IM Cefazolin 1-2 g TID x  2/52 then Caps Cephalexin 1-2 g QID

OR

  • IV Clindamycin 600mg TID initially and continue with Caps Clindamycin 300 - 450mg QID

 

_OM due to β-haemolytic streptococci: 

  • IV or IM Benzyl penicillin 2 million IU (1.2 g) every 4 - 6 hrs initially and continue with Caps Amoxicillin 1gm QID or TID for a total duration of 2 - 4 wks

 

_OM due to Salmonella spp:

  • Tabs Ciprofloxacin 750gm BD x 6/52

 

_OM in children aged > 5 yrs (mainly caused by S. aureus)

  • IV or IM Cloxacillin 25 - 50mg/kg (maximum 2g) every 4 - 6 hours for 4 - 6 days, followed by Caps Cloxacillin 25mg/kg (maximum 500mg) QID for 3 - 4 weeks

OR

  • IV or IM Ceftriaxone  50 - 75mg/kg (maximum 1g) daily for 4 - 6 days, followed by Caps Cloxacillin 25mg/kg (maximum 500mg) or Caps Cephalexin 25mg/kg (maximum 500mg) QID

OR

  • IV or IM Cefazolin 15mg/kg (maximum 1g) TID for 4 - 6 days followed by Caps Cephalexin 25mg/kg (maximum 500mg) QID

 OR

  • IV Clindamycin 10mg/kg (maximum 450mg) QID for 4 - 6 days followed by Caps clindamycin 10mg/kg (maximum 450mg) QID

 

_OM in children aged up to 5 yrs (mainly due to Haemophilus influenzae)

  • IV or IM Cloxacillin 25 - 50mg/kg (maximum 2g) every 4 - 6 hrs PLUS IV or IM Ceftriaxone 50 - 75mg/kg (maximum 1g) daily until clinical improvement occurs followed by Syrup Amoxicillin 15mg/kg + Clavulanic acid (maximum 500mg) TID

 

_OM for neonates (mainly due to Haemophilus influenzae)

  • IV /IM Cloxacillin 25 - 50mg/kg (maximum 2g) every 4 - 6 hours PLUS IV Cefotaxime 50 - 75mg/kg (maximum 2g) TID until clinical improvement occurs, followed by Suspension Amoxicillin 15mg/kg + Clavulanic acid  (maximum 500mg) TID

 

_OM due to S. aureus in Children aged 2 months to 5 years

  • IV/IM Cloxacillin 25 - 50mg/kg (maximum 2g) every 4 - 6 hours PLUS IV/IM Ceftriaxone 50 - 75mg/kg (maximum 1g) daily until clinical improvement occurs, followed by Suspension Cloxacillin 12.5mg/kg (maximum 500mg)

 

_OM due to S. aureus in neonates

  • IV/IM Cloxacillin 25 - 50mg/kg (maximum 2g) every 4 - 6 hours PLUS IV Cefotaxime 50 - 75mg/kg (maximum 2g) TID until clinical improvement occurs, followed by Suspension Cloxacillin 12.5mg/kg (maximum 500mg) QID

 

_OM due to Salmonella spp in Children aged 2 months to 5 years

  • IV/IM Cloxacillin 25 - 50mg/kg (maximum 2g) every 4 - 6 hours PLUS IV/IM Ceftriaxone 50 - 75mg/kg (maximum 1g) daily until clinical improvement occurs, followed by either Suspension Sulfamethoxazole 20mg/kg + Trimethoprim 4mg/kg (maximum 800mg + 160 mg) BID or  Suspension Amoxicillin 5 - 15mg/kg (maximum 1g) TID or  Suspension Ciprofloxacin 10 - 15mg/kg (maximum 500mg) BD

 

## Antibiotic regimes outside the Essential Drug List (EDL)

Acute hematogenous OM

  • IV Vancomycin 1gm BD when MRSA is prevalent in a community

OR

  • IV Ceftazidime 2gm TID

OR

  • IV Cefepime 2gm BD

 

Chronic OM arising from a contiguous soft-tissue focus (e.g. diabetes)

  • Treatment needs to be effective against anaerobic organisms in addition to gram-positive and gram-negative aerobes
  • IV Ampicillin/sulbactam 3gm QID

OR

  • IV Piperacillin/tazobactam 3.375gm QID

 OR

  • Add Vancomycin 1gm BD is when infection is severe or MRSA is prevalent.

 

OM from contiguous spread of infection

  • IV Piperacillin-tazobactam 3.375gm IV QID

OR

  • IV Ampicillin-sulbactam 3gm QID

OR

  • IV Ticarcillin-clavulanate 3.1gm QID in Patients with penicillin allergy

OR

  • IV Clindamycin 600mg QID

OR

  • IV Metronidazole 500 mg IV TID PLUS Ciprofloxacin 750 mg daily orally or 400 mg IV BD or Levofloxacin 750 mg orally daily or moxifloxacin 400 mg orally daily

 

If MRSA is suspected add;

  • IV Vancomycin 15 mg/kg BD

 

If Vancomycin is contraindicated in MRSA use;

  • Linezolid Orally or IV

 

Oral therapy after IV treatment for patients with OM from contiguous spread of infection:

  • Tabs Amoxicillin-clavulanate 875 mg/125 mg BD OR
  • Tabs Ciprofloxacin 750 mg BD PLUS Clindamycin 300-450 mg QID OR
  • Tabs Levofloxacin 750 mg daily PLUS caps Clindamycin 300-450 mg PO QID or
  • Tabs Moxifloxacin 400 mg daily.

 

## Surgery

  • Drainage of coexisting paravertebral or epidural abscesses
  • Debridement and sequestrectomy of necrotic tissues (in case of poor prognosis and/or antibiotic failure)
  • Grafting of skin or pedicle to close large surgical lesions

Amputation is indicated in OM in cases of arterial insufficiency, major nerve paralysis, nonfunctional limb-stiffness, and malignant change

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