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:
- Acute osteomyelitis (1 to 2 weeks) versus chronic osteomyelitis (3 to 6 months), though this classification is not necessarily helpful
- Etiology and location, including the presence of orthopedic hardware or joint prosthesis
- Cierny-Mader classification based on area of bone involvement1
- Type I: medullary
- Type II: superficial
- Type III: localized
- Type IV: diffuse
- Immune status and frailty of host
Microbiology
- Based on 2
| 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
- Poorer outcomes
- Commonly involves Staphylococcus aureus iwht a mix of other bacteria
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 exist3
- Bioavailability likely still important
- Empiric antimicrobials should generally cover MRSA, susceptible Gram-positives, and common Gram-negatives
- For example, vancomycin plus ceftriaxone
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 tid |
OVIVA Trial
- Oral therapy non-inferior to intravenous therapy for bone and joint infections requiring 6+ weeks of therapy4
- Patients were randomized after at least 7 days of appropriate IV antibiotics
- Oral regimens included fluoroquinolones (41%), combination with ciprofloxacin/clindamycin or ciprofloxacin/doxycycline (14%), beta lactams (15%), macrolides or lincosamides (11%), tetracyclines (9%), and other antibiotics (9%)
References
- ^ 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.
- ^ 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.
- ^ 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.
