Osteomyelitis

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Background

  • Inflammation of the bone which involves the medullary cavity, in comparison to osteitis (a distinction made on MRI but not clinically relevant)
  • Classified by:

Microbiology

  • Based on 1
Species Upper Extremity Vertebral Lower Extremity PJI Trauma of Fracture Hematogenous Foot and Ankle
Gram-positive bacteria Staphylococcus aureus 10-40% 15-60% 20-30% 20-40% 40% 45-55%
Coagulase-negative staphylococci 10-20% 5-40% 25-35% 10-40% <5% <5%
Streptococcus species 5-10% 5-10% <5% 5-10% 5-10% 5-20%
Enterococcus species <5% 5-15% <5% 5% <5% 5%
Diphtheroids <5% 5% <5% 5% <5% <5%
Cutibacterium acnes 30-50% in shoulder 10-15% spinal fusion
Gram-negative bacteria Overall 5-10% 10-40% 5-10% 20% 10-15% 35-55%
Pseudomonas species <5% 5-10% <5% 5-10% 5-10% 10-20%
Enterobacteriaceae <5% 10-20% <5% 5-20% 5% 10-15%
HACEK group <5% <5% <5% <5% <5% <5%
Polymicrobial bacteria 10-25% 15-30% 10-20% 20-30% 20 30-80%
Fungi <5% <5% <5% <5% <5% <5%
  • Polymicrobial infections are more common in trauma-related OM, PJI, and diabetic foot infections

Diagnosis

  • Bone biopsy for histology and culture is the gold standard
  • However, diagnosis is usually made based on a combination of physical exam, lab tests, and imaging
    • Physical exam findings: fever, constitutional symptoms, sinus tract, joint pain and swelling, cellulitis at the site
    • Blood tests: elevated WBC or CRP, positive blood cultures
      • Novel tests: alpha-defensin, D-dimer, synolvial IL-6, and synovial CRP
    • Imaging: MRI is the most sensitive; can also use bone scan and labelled WBC scan, or plain film x-ray or CT (if more chronic)

Management

  • No clinically meaningful differences in bone penetration between classes of antibiotics exist2
  • Bioavailability likely still important
  • Empiric antimicrobials should generally cover MRSA, susceptible Gram-positives, and common Gram-negatives

Parenteral Antimicrobials

Organism Antimicrobial Options
MSSA nafcillin 2 g IV q4h
oxacillin 2 g IV q4h
cefazolin 2 g IV q8h
flucloxacillin 2 g IV q6h
ceftriaxone 2 g IV q24h
MRSA vancomycin 20 mg/kg load followed by 15-20 mg IV q8-12h
daptomycin 6 to 10 mg/kg IV daily
teicoplanin 12 mg/kg IV q12h for 3 to 5 doses followed by q24h
Adjunctive staphylococcal agent rifampin 300 to 450 mg PO bid
fusidic acid 500 mg PO tid
Gram-negative bacteria ciprofloxacin 750 mg PO big to 400 mg IV q12h
levofloxacin 750 mg PO/IV daily
ceftriaxone 2 g IV q24h
ceftazidime 2 g IV q8h
cefepime 2 g IV q8-12h
ertapenem 1 g IV q24h
meropenem 1 g IV q8h
Pseudomonas aeruginosa ciprofloxacin 400 mg IV q8h
Enterococcus ampicillin 12 g continuous IV q24h
ampicillin 2 g IV q4h
penicillin G 20 to 24 million units continuous IV q24h
penicillin G 3-4 million units IV q4h
vancomycin 20 mg/kg IV load followed by 15 mg/kg IV q12h (max 2 g per dose)
daptomycin 6 to 10 mg/kg IV daily
teicoplanin 12 mg/kg IV q12h for 3 to 5 doses, followed by q24h
ampicillin as above, PLUS ceftriaxone 2 g IV q12-24h
penicillin-susceptible streptococci ampicillin 12 g continuous IV q24h
ampicillin 2 g IV q4h
penicillin G 20 to 24 million units continuous IV q24h
penicillin G 3-4 million units IV q4h
ceftriaxone 2 g IV q24h
vancomycin 20 mg/kg IV load followed by 15 mg/kg IV q12h (max 2 g per dose)
Cutibacterium acnes penicillin G 20 to 24 million units continuous IV q24h
penicillin G 3-4 million units IV q4h
ceftriaxone 2 g IV q24h

Oral Antimicrobials

Organism Antibiotic Options
MSSA cefadroxil 500 to 1000 mg PO bid
cephalexin 500 mg PO tid to qid, or 1000 mg PO bid to tid
dicloxacillin 500 mg PO tid to qid
flucloxaxillin 500 mg PO tid to qid
MRSA TMP-SMX DS 1 tablet PO bid
doxycycline 100 mg PO bid
minocycline 100 mg PO bid
clindamycin 600 mg PO tid
Gram-negative bacteria TMP-SMX DS 1 tablet PO bid
ciprofloxacin 500 mg PO bid
levofloxacin 500 mg PO daily
penicillin-susceptible streptococci and enterococci amoxicillin 500 mg PO bid to tid
penicillin VK 500 mg PO bid to tid
Cutibacterium acnes amoxicillin 500 mg PO bid to tid
penicillin VK 500 mg PO bid to tidO

OVIVA Trial

  1.   Cierny G, Mader JT, Penninck JJ. A clinical staging system for adult osteomyelitis. Clinical Orthopaedics and Related Research. 2003;(414):7–24. doi: 10.1097/01.blo.0000088564.81746.62

References

  1. ^  Elysia A. Masters, Benjamin F. Ricciardi, Karen L. de Mesy Bentley, T. Fintan Moriarty, Edward M. Schwarz, Gowrishankar Muthukrishnan. Skeletal infections: microbial pathogenesis, immunity and clinical management. Nature Reviews Microbiology. 2022. doi:10.1038/s41579-022-00686-0.
  2. ^  Cornelia B. Landersdorfer, Jürgen B. Bulitta, Martina Kinzig, Ulrike Holzgrabe, Fritz Sörgel. Penetration of Antibacterials into Bone. Clinical Pharmacokinetics. 2009;48(2):89-124. doi:10.2165/00003088-200948020-00002.
  3. ^  Ho-Kwong Li, Ines Rombach, Rhea Zambellas, A. Sarah Walker, Martin A. McNally, Bridget L. Atkins, Benjamin A. Lipsky, Harriet C. Hughes, Deepa Bose, Michelle Kümin, Claire Scarborough, Philippa C. Matthews, Andrew J. Brent, Jose Lomas, Roger Gundle, Mark Rogers, Adrian Taylor, Brian Angus, Ivor Byren, Anthony R. Berendt, Simon Warren, Fiona E. Fitzgerald, Damien J.F. Mack, Susan Hopkins, Jonathan Folb, Helen E. Reynolds, Elinor Moore, Jocelyn Marshall, Neil Jenkins, Christopher E. Moran, Andrew F. Woodhouse, Samantha Stafford, R. Andrew Seaton, Claire Vallance, Carolyn J. Hemsley, Karen Bisnauthsing, Jonathan A.T. Sandoe, Ila Aggarwal, Simon C. Ellis, Deborah J. Bunn, Rebecca K. Sutherland, Gavin Barlow, Cushla Cooper, Claudia Geue, Nicola McMeekin, Andrew H. Briggs, Parham Sendi, Elham Khatamzas, Tri Wangrangsimakul, T.H. Nicholas Wong, Lucinda K. Barrett, Abtin Alvand, C. Fraser Old, Jennifer Bostock, John Paul, Graham Cooke, Guy E. Thwaites, Philip Bejon, Matthew Scarborough. Oral versus Intravenous Antibiotics for Bone and Joint Infection. New England Journal of Medicine. 2019;380(5):425-436. doi:10.1056/nejmoa1710926.