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 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 mos.)-Adult
- 1.2.1 MRSA possible
- Preferred regimen: Vancomycin 40 div q6–8h
- 1.2.2 MRSA unlikely
- Note: Add Ceftazidime 50 q8h or Cefepime 150 div q8h if Gm-neg. bacilli on Gram stain
- 1.3 Newborn (<4 mos.)
- 1.3.1 MRSA possible
- Preferred regimen: Vancomycin AND (Ceftazidime 2 g IV q8h or Cefepime 2 g IV q12h)
- 1.3.2 MRSA unlikely
- Preferred regimen: (Nafcillin OR Oxacillin) AND (Ceftazidime OR Cefepime)
- 2. Specific therapy
- 2.1 MSSA
- Preferred regimen: Nafcillin 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 and treat for 6 weeks.
- Revascularize if possible.
Puncture Wound Osteomyelitis
- Long bone, post-internal fixation of fracture [3]
- 1. S. aureus or P. aeruginosa
- Preferred regimen: Vancomycin 1 g IV q12h AND (Ceftazidime OR Cefepime)
- Alternative regimen (1): Linezolid 600 mg IV/PO bidNAI AND Ceftazidime
- Alternative regimen (2): Linezolid 600 mg IV/PO bidNAI AND Cefepime
- 2. Gm-neg. 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; consider when ESBL-producing pathogens suspected)
- 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 (for more severe cases) AND Clindamycin 150–300 mg PO qid
- 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. Chronic Osteomyelitis in Adults – Pathogen-Based Therapy [5]
- 1.1 OSSA
- 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 ORSA
- 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
- 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
- 1. OSSA or coagulase-negative staphylococci
- Preferred regimen (1): Oxacillin 2 g IV q6h
- Preferred regimen (2): Cefazolin 1–2 g IV q8h
- Alternative regimen: Levofloxacin 750 mg PO qd AND Rifampin 300 mg PO bid
- 2. ORSA
- Preferred regimen: Vancomycin 1 g IV q12h
- Alternative regimen (1): Daptomycin 6 mg/kg IV q24h
- Alternative regimen (2): Levofloxacin 500–750 mg/day PO/IV AND Rifampin 600–900 mg PO qd
- 3. Streptococcus
- Preferred regimen: Penicillin G 5 MU IV q6h
- Alternative regimen: Ceftriaxone 2 g IV q24h
- 4. Enterobacteriaceae, quinolone-susceptible
- Preferred regimen: Ciprofloxacin 750 mg PO q12h
- Alternative regimen: Ceftriaxone 2 g IV q24h
- 5. Enterobacteriaceae, quinolone-resistant
- Preferred regimen: Imipenem 500 mg IV q6h
- 6. Pseudomonas aeruginosa
- Preferred regimen: (Cefepime 2 g IV q8h OR Ceftazidime 2 g IV q8h for 2–4 weeks), followed by Ciprofloxacin 750 mg PO bid
- Alternative regimen: Piperacillin–Tazobactam 750 mg PO q12h for 2–4 weeks, followed by Ciprofloxacin 750 mg PO bid
- 7. Anaerobes
- Preferred regimen: Piperacillin–Tazobactam 750 mg PO q12h for 2–4 weeks, followed by Ciprofloxacin 750 mg PO bid
- Alternative regimen (1): Penicillin G 5 MU IV q6h
- Alternative regimen (2): Ceftriaxone 2 g IV q24h (against gram-positive anaerobes)
- Alternative regimen (3): Metronidazole 500 mg PO tid (against gram-negative anaerobes)
Sternal Osteomyelitis
- Osteomyelitis, sternal [8]
- Preferred regimen: Vancomycin 1 g IV q12h (If over 100kg, 1.5 g IV q12h)
- Alternative regimen: Linezolid 600 mg po/IVNAI bid
Candidal Osteomyelitis
- Osteomyelitis, candidal [9]
- 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 [10]
- Preferred regimen: Ciprofloxacin 400 mg IV q12h
- Alternative regimen: Levofloxacin 750 mg IV q24h
Spinal Implant-Associated Osteomyelitis
- Culture, treat & then suppress until fusion occurs
- Main parenteral antimicrobial therapy
- Preferred regimen: Beta-lactam antibiotic OR Vancomycin
- Suppressive antimicrobial therapy strategy
- Preferred regimen: Beta-lactam antibiotic OR Minocycline
- 2. Onset after 30 days
- Remove implant, culture & treat
- Main parenteral antimicrobial therapy
- Preferred regimen: Beta-lactam antibiotic OR Vancomycin OR Combination therapy
- Suppressive antimicrobial therapy strategy
- Preferred regimen: Combination therapy OR Minocycline
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.
- ↑ Gentry LO (1991). "Oral antimicrobial therapy for osteomyelitis". Ann Intern Med. 114 (11): 986–7. PMID 2024868.
- ↑ Marschall J, Bhavan KP, Olsen MA, Fraser VJ, Wright NM, Warren DK (2011). "The impact of prebiopsy antibiotics on pathogen recovery in hematogenous vertebral osteomyelitis". Clin Infect Dis. 52 (7): 867–72. doi:10.1093/cid/cir062. PMC 3106232. PMID 21427393.
- ↑ 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.
- ↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
- ↑ Kowalski TJ, Berbari EF, Huddleston PM, Steckelberg JM, Mandrekar JN, Osmon DR (2007). "The management and outcome of spinal implant infections: contemporary retrospective cohort study". Clin Infect Dis. 44 (7): 913–20. doi:10.1086/512194. PMID 17342641.