Osteomyelitis medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
The mainstay of therapy for osteomyelitis typically involves complete surgical debridement followed by antimicrobial therapy against suspected pathogens. Antimicrobial therapy is based on predisposing host factors and local resistance patterns. The standard recommendation for the treatment of chronic osteomyelitis is ≥ 4–6 weeks of parenteral antibiotics. However, oral antimicrobial agents may achieve adequate concentrations in the bone with similar cure rates as compared to parental administration, and may be considered in selected cases.
Medical Therapy
- The mainstay of therapy for osteomyelitis is antimicrobial therapy and surgical debridement.
- Antibiotic regimens should be targeted whenever possible (blood culture or biopsy if blood cultures are negative or equivocal), or should be tailored to the clinical situation.
Antimicrobial Regimens
Hematogenous Osteomyelitis
- 1. Empiric antimicrobial therapy [1]
- 1.1 Adult (>21 yrs)
- 1.1.1 MRSA possible
- Preferred regimen: Vancomycin 1 g IV q12h (if over 100 kg, 1.5 g IV q12h)
- 1.1.2 MRSA unlikely
- 1.2 Children (>4 months)
- 1.2.1 MRSA possible
- Preferred regimen: Vancomycin 40 mg/kg/day IV q6–8h
- 1.2.2 MRSA unlikely
- Note: Add Ceftazidime 50 mg/kg IV q8h or Cefepime 150 mg/kg/day IV q8h if Gram-negative bacilli on Gram stain.
- 2. Pathogen-directed antimicrobial therapy
- 2.1 MSSA
- Preferred regimen: Nafcillin 2 g IV q4h OR Oxacillin 2 g IV q4h OR Cefazolin 2 g IV q8h
- Alternative regimen: Vancomycin 1 g IV q12h (if over 100 kg, 1.5 g IV q12h)
- 2.2 MRSA
- Preferred regimen: Vancomycin 1 g IV q12h
- Alternative regimen: Linezolid 600 mg q12h IV/PO ± Rifampin 300 mg po/IV bid
Contiguous Osteomyelitis with Vascular Insufficiency
- Osteomyelitis, contiguous with vascular insufficiency [2]
- Debride overlying ulcer and send bone specimen for histology and culture.
- No empiric antimicrobial therapy unless acutely ill.
- Antibiotic therapy should be based on culture results
- Treatment duration is at least 6 weeks.
- Revascularize if possible.
Open Fracture Osteomyelitis
- Long bone, post-internal fixation of fracture [3]
- 1. S. aureus or P. aeruginosa
- Preferred regimen: Vancomycin 1 g IV q12h AND (Ceftazidime 2 g IV q8h OR Cefepime 2 g IV q8h)
- Alternative regimen (1): Linezolid 600 mg IV/PO bid AND Ceftazidime 2 g IV q8h
- Alternative regimen (2): Linezolid 600 mg IV/PO bid AND Cefepime 2 g IV q8h
- 2. Gram negative bacilli
- Preferred regimen (1): Ciprofloxacin 750 mg PO bid
- Preferred regimen (2): Levofloxacin 750 mg PO qd
Diabetic Foot Osteomyelitis
- 1. Chronic infection or recent antibiotic use [4]
- Preferred regimen (1): Levofloxacin 750 mg IV/PO q24h
- Preferred regimen (2): Cefoxitin 1 g IV q4h (or 2 g IV q6–8h)
- Preferred regimen (3): Ceftriaxone 1–2 g/day IV/IM q12–24h
- Preferred regimen (4): Ampicillin-Sulbactam 1.5–3 g IV/IM q6h
- Preferred regimen (5): Moxifloxacin 400 mg IV/PO q24h
- Preferred regimen (6): Ertapenem 1 g IV/IM q24h
- Preferred regimen (7): Tigecycline 100 mg IV THEN 50 mg IV q12h (active against MRSA)
- Preferred regimen (8): Imipenem-Cilastatin 0.5–1 g IV q6–8h (Not active against MRSA)
- Alternative regimen (1): Levofloxacin 750 mg IV/PO q24h AND Clindamycin 150–300 mg PO qid
- Alternative regimen (2): Ciprofloxacin 600–1200 mg/day IV q6–12h AND Clindamycin 150–300 mg PO qid
- Alternative regimen (3): Ciprofloxacin 1200–2700 mg IV q6–12h AND Clindamycin 150–300 mg PO qid (for more severe cases)
- 2. High risk for MRSA
- Preferred regimen (1): Linezolid 600 mg IV/PO q12h
- Preferred regimen (2): Daptomycin 4 mg/kg IV q24h
- Preferred regimen (3): Vancomycin 15–20 mg/kg IV q8–12h (trough: 10–20 mg/L)
- 3. High risk for Pseudomonas aeruginosa
- Preferred regimen: Piperacillin–Tazobactam 3.375 g IV q6–8h
- 4. Polymicrobial infection
- Preferred regimen: (Vancomycin 15–20 mg/kg IV q8–12h (trough: 10–20 mg/L) OR Linezolid 600 mg IV/PO q12h OR Daptomycin 4 mg/kg IV q24h) AND (Piperacillin–Tazobactam 3.375 g IV q6–8h OR Imipenem–Cilastatin 0.5–1 g IV q6–8h OR Ertapenem 1 g IV/IM q24h OR Meropenem 1 g IV q8h)
- Alternative regimen: (Vancomycin 15–20 mg/kg IV q8–12h (trough: 10–20 mg/L) OR Linezolid 600 mg IV/PO q12h OR Daptomycin 4 mg/kg IV q24h) AND (Ceftazidime 2 g IV q8h OR Cefepime 2 g IV q8h OR Aztreonam 2 g IV q6–8h) AND Metronidazole 15 mg/kg IV, then 7.5 mg/kg IV q6h
Chronic Osteomyelitis
- 1. Pathogen-directed antimicrobial therapy [5]
- 1.1 MSSA
- Preferred regimen (1): Oxacillin 1.5–2 g IV q4h for 4–6 weeks
- Preferred regimen (2): Cefazolin 1–2 g IV q8h for 4–6 weeks
- Alternative regimen (1): Vancomycin 15 mg/kg IV q12h for 4–6 weeks
- Alternative regimen (2): Oxacillin 1.5–2 g IV q4h for 4–6 weeks AND Rifampin 600 mg PO qd
- 1.2 MRSA
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h for 4–6 weeks
- Preferred regimen (2): Daptomycin 6 mg/kg IV q24h
- Alternative regimen (1): Linezolid 600 mg PO/IV q12h for 6 weeks ± Rifampin 600–900 mg PO qd
- Alternative regimen (2): Levofloxacin 500–750 mg/day PO/IV ± Rifampin 600–900 mg PO qd
- 1.3 Penicillin-sensitive Streptococcus
- Preferred regimen (1): Penicillin G 20 MU/day IV continuously or q4h for 4–6 weeks
- Preferred regimen (2): Ceftriaxone 1–2 g IV/IM q24h for 4–6 weeks
- Preferred regimen (3): Cefazolin 1–2 g IV q8h for 4–6 weeks
- Alternative regimen: Vancomycin 15 mg/kg IV q12h for 4–6 weeks
- 1.4 Enterococcus or Streptococcus (MIC≥ 0.5 μg/mL) or Abiotrophia or Granulicatella
- Preferred regimen (1): Penicillin G 20 MU/day IV continuously or q4h for 4–6 weeks ± Gentamicin 1 mg/kg IV/IM q8h for 1–2 weeks
- Preferred regimen (2): Ampicillin 12 g/day IV continuously or q4h for 4–6 weeks ± Gentamicin 1 mg/kg IV/IM q8h for 1–2 weeks
- Alternative regimen: Vancomycin 15 mg/kg IV q12h for 4–6 weeks ± Gentamicin 1 mg/kg IV/IM q8h for 1–2 weeks
- 1.5 Enterobacteriaceae
- Preferred regimen (1): Ceftriaxone 1–2 g IV/IM q24h for 4–6 weeks
- Preferred regimen (2): Ertapenem 1 g IV q24h
- Alternative regimen (1): Levofloxacin 500–750 mg PO qd
- Alternative regimen (2): Ciprofloxacin 500–750 mg PO bid for 4–6 weeks
- 1.6 Pseudomonas aeruginosa
- Preferred regimen (1): Cefepime 2 g IV q12h
- Preferred regimen (2): Meropenem 1 g IV q8h
- Preferred regimen (3): Imipenem 500 mg IV q6h for 4–6 weeks
- Alternative regimen (1): Ciprofloxacin 750 mg PO q12h
- Alternative regimen (2): Ceftazidime 2 g IV q8h for 4–6 weeks
- 2. Chronic Osteomyelitis in Children – Pathogen-Based Therapy
- 2.1 Group A beta-hemolytic Streptococcus, Haemophilus influenzae type B and Streptococcus pneumoniae
- Preferred regimen (1): Ampicillin 150–200 mg/kg/day q6h
- Preferred regimen (2): Amoxicillin 150–200 mg/kg/day q6h
- Alternative regimen: Chloramphenicol 75 mg/kg/day q8h
Vertebral Osteomyelitis
- Pathogen-directed antimicrobial therapy[6]
- 1. OSSA or coagulase-negative staphylococci
- Preferred regimen (1): Nafcillin sodium or Oxacillin 1.5-2 g IV q4-6h or continuous infusion for 6 weeks
- Preferred regimen (2): Cefazolin 1-2 g IV q8h for 6 weeks
- Preferred regimen (3): Ceftriaxone 2 g IV q24h for 6 weeks
- Alternative regimen (1): Vancomycin IV 15-20 mg/kg q12 hd for 6 weeks
- Alternative regimen (2): Daptomycin 6-8 mg/kg IV q24h for 6 weeks
- Alternative regimen (3): Linezolid 600 mg PO/IV q12h for 6 weeks
- Alternative regimen (4): Levofloxacin 500-750 mg PO q24h for 6 weeks
- Alternative regimen (5): Rifampin PO 600 mg q24h for 6 weeks
- Alternative regimen (6): Clindamycin IV 600-900 mg q8h for 6 weeks
- 2. ORSA
- Preferred regimen: Vancomycin IV 15-20 mg/kg q12h for 6 weeks
- Alternative regimen: Daptomycin 6-8 mg/kg IV q24h OR Linezolid 600 mg PO/IV q12 h OR Levofloxacin PO 500–750 mg PO q24 h AND Rifampin PO 600 mg q24h for 6 weeks
- 3. β-hemolytic Streptococci
- Preferred regimen: Penicillin G 20-24 million units IV q24h continuously or in 6 divided doses for 6 weeks
- Preferred regimen: Ceftriaxone 2 g IV q24h for 6 weeks
- Alternative regimen: Vancomycin IV 15-20 mg/kg q12h for 6 weeks
- 4. Enterobacteriaceae
- Preferred regimen: Cefepime 2 g IV q12h for 6 weeks
- Preferred regimen: Ertapenem 1 g IV q24h for 6 weeks
- Alternative regimen: Ciprofloxacin 500-750 mg PO q12h or 400 mg IV q12h for 6 weeks
- 5. Pseudomonas aeruginosa
- Preferred regimen: Cefepime 2 g IV q8-12h for 6 weeks
- Preferred regimen: Meropenem 1 g IV q8h for 6 weeks
- Preferred regimen: Doripenem 500 mg IV q8h for 6 weeks
- Alternative regimen: Ciprofloxacin 750 mg PO q12h or 400 mg IV q8h) for 6 weeks
- Alternative regimen: Aztreonam 2 g IV q8h for 6 weeks
- Alternative regimen: Ceftazidime 2 g IV q8h for 6 weeks
- 6. Enterococcus, penicillin susceptible
- Preferred regimen: Penicillin G 20-24 million units IV q24h continuously or in 6 divided doses
- Preferred regimen: Ampicillin sodium 12 g IV q24h continuously or in 6 divided doses
- Alternative regimen: Vancomycin 15-20 mg/kg IV q12h
- Alternative regimen: Daptomycin 6 mg/kg IV q24h
- Alternative regimen: Linezolid 600 mg PO or IV q12h
- 7. Enterococcus, penicillin resistant
- Preferred regimen: Vancomycin IV 15-20 mg/kg q12h
- Alternative regimen: Daptomycin 6 mg/kg IV q24h
- Alternative regimen: Linezolid 600 mg PO or IV q12h
- 8. Propionibacterium acnes
- Preferred regimen: Penicillin G 20 million units IV q24h continuously or in 6 divided doses for 6 weeks
- Preferred regimen: Ceftriaxone 2 g IV q24h for 6 weeks
- Alternative regimen: Clindamycin 600-900 mg IV q8h for 6 weeks
- Alternative regimen: Vancomycin IV 15-20 mg/kg q12h for 6 weeks
- 9. Salmonella species
- Preferred regimen: Ciprofloxacin PO 500 mg q12h or IV 400 mg q12h for 6-8 weeks
- Alternative regimen: Ceftriaxone 2 g IV q24h for 6-8 weeks
Sternal Osteomyelitis
- Osteomyelitis, sternal [7]
- Preferred regimen: Vancomycin 1 g IV q12h (If over 100kg, 1.5 g IV q12h)
- Alternative regimen: Linezolid 600 mg PO/IV bid
Candidal Osteomyelitis
- Osteomyelitis, candidal [8]
- Preferred regimen (1): Fluconazole 400 mg/day (6 mg/kg/day) PO for 6–12 months
- Preferred regimen (2): Amphotericin B 3–5 mg/kg/day PO for several weeks THEN Fluconazole for 6–12 months
- Alternative regimen (1): Anidulafungin 200 mg loading dose THEN 100 mg/day PO
- Alternative regimen (2): Caspofungin 70mg loading dose THEN 50 mg/day PO
- Alternative regimen (3): Micafungin 100 mg/day PO
- Alternative regimen (4): Amphotericin B deoxycholate 0.5–1 mg/kg/day PO for several weeks THEN Fluconazole for 6–12 months
- Note: Duration of therapy usually is prolonged (6–12 months); Surgical debridement is frequently necessary
Hemoglobinopathy-Associated Osteomyelitis
- Osteomyelitis, hemoglobinopathy [9]
- Preferred regimen: Ciprofloxacin 400 mg IV q12h
- Alternative regimen: Levofloxacin 750 mg IV q24h
References
- ↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
- ↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
- ↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
- ↑ Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG; et al. (2013). "2012 infectious diseases society of america clinical practice guideline for the diagnosis and treatment of diabetic foot infections". J Am Podiatr Med Assoc. 103 (1): 2–7. PMID 23328846.
- ↑ Spellberg B, Lipsky BA (2012). "Systemic antibiotic therapy for chronic osteomyelitis in adults". Clin Infect Dis. 54 (3): 393–407. doi:10.1093/cid/cir842. PMC 3491855. PMID 22157324.
- ↑ Berbari EF, Kanj SS, Kowalski TJ, Darouiche RO, Widmer AF, Schmitt SK; et al. (2015). "2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adultsa". Clin Infect Dis. 61 (6): e26–46. doi:10.1093/cid/civ482. PMID 26229122.
- ↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
- ↑ Pappas PG, Kauffman CA, Andes D, Benjamin DK, Calandra TF, Edwards JE; et al. (2009). "Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America". Clin Infect Dis. 48 (5): 503–35. doi:10.1086/596757. PMID 19191635.
- ↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.