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

Acute Hematogenous Osteomyelitis

The following table summarizes the treatment for acute hematogenous osteomyelitis.

Pathogens		Age group specific therapy
		Adult (>21 yr)	Children (4 m-21yr)
Empiric	MRSA possible	Vancomycin 1 g IV q12h (if over 100 kg, 1.5 g IV q12h)	Vancomycin 40 mg/kg/day IV q6–8h
	MRSA unlikely	Nafcillin 2 g IV q4h OR Oxacillin 2 g IV q4h	Nafcillin 37 mg/kg IV q6h (maximum dose 8–12 g/day) OR Oxacillin 37 mg/kg IV q6h (maximum dose 8–12 g/day)
Pathogen directed	MSSA	Nafcillin 2 g IV q4h OR Oxacillin 2 g IV q4h OR Cefazolin 2 g IV q8h	Cefazolin (100 mg/kg/24 hr divided q8h IV) OR Nafcillin (150-200 mg/kg/24 hr divided q6h)
	MRSA	Vancomycin 1 g IV q12h Alternative: Linezolid 600 mg q12h IV/PO ± Rifampin 300 mg po/IV bid	Vancomycin (60 mg/kg/24 hr divided q6h IV)
	Streptococcus agalactiae (Group B Streptococcus)	Penicillin	Penicillin (250,000 to 400,000 units/kg per day divided in 4 to 6 doses; maximum dose 24 million units per day)
	Streptococcus pyogenes (Group A Streptococcus)	Penicillin	Penicillin (250,000 to 400,000 units/kg per day divided in 4 to 6 doses; maximum dose 24 million units per day)
	Streptococcus pneumoniae (Pneumococcus) Penicillin-susceptible	Penicillin	Penicillin (250,000 to 400,000 units/kg per day divided in 4 to 6 doses; maximum dose 24 million units per day)
	Streptococcus pneumoniae (Pneumococcus) Penicillin-nonsusceptible	Cefotaxime OR Ceftriaxone OR Clindamycin OR Linezolid	Cefotaxime (150 to 200 mg/kg per day divided in 3 or 4 doses; maximum dose 12 g/day) OR Ceftriaxone (80 to 100 mg/kg per day divided in 1 or 2 doses; maximum dose 4 g/day) OR Clindamycin (40 mg/kg per day divided in 3 or 4 doses; maximum dose 2.7 g/day) OR Linezolid (<12 years: 30 mg/kg per day in 3 doses, ≥12 years: 600 mg twice per day)
	Haemophilus influenzae type b	Cefotaxime OR Ceftriaxone OR Cefuroxime	Cefotaxime (150 to 200 mg/kg per day divided in 3 or 4 doses; maximum dose 12 g/day) OR Ceftriaxone (80 to 100 mg/kg per day divided in 1 or 2 doses; maximum dose 4 g/day) OR Cefuroxime
	Kingella kingae	Penicillin OR Cefotaxime OR Ceftriaxone	Penicillin (250,000 to 400,000 units/kg per day divided in 4 to 6 doses; maximum dose 24 million units per day) OR Cefotaxime (150 to 200 mg/kg per day divided in 3 or 4 doses; maximum dose 12 g/day) OR Ceftriaxone (80 to 100 mg/kg per day divided in 1 or 2 doses; maximum dose 4 g/day)

Contiguous Osteomyelitis with Vascular Insufficiency

• Osteomyelitis, contiguous with vascular insufficiency

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• Preferred regimen: Ciprofloxacin 400 mg IV q12h
• Alternative regimen: Levofloxacin 750 mg IV q24h