Osteomyelitis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2]

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)

_{† Risk factors for MRSA include:}

_{Recent hospitalization, residence in a long-term care facility, recent antibiotic therapy, HIV infection, men who have sex with men, injection drug use, hemodialysis, incarceration, military service, sharing needles, razors, or other sharp objects, sharing sports equipment, diabetes, prolonged hospital stay, swine farming}

Chronic Osteomyelitis

Treatment options for chronic ostemyelitis (based on pathogen) in children include:

• 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

The table below summarizes the treatment options for chronic osteomyelitis in adults.

Chronic osteomyelitis
Pathogen	Preferred regimen	Alternative regimen
MSSA	Oxacillin 1.5–2 g IV q4h for 4–6 weeks OR Cefazolin 1–2 g IV q8h for 4–6 weeks	Vancomycin 15 mg/kg IV q12h for 4–6 weeks OR Oxacillin 1.5–2 g IV q4h for 4–6 weeks AND Rifampin 600 mg PO qd
MRSA	Vancomycin 15 mg/kg IV q12h for 4–6 weeks OR Daptomycin 6 mg/kg IV q24h OR Teicoplanin 6 to 12 mg/kg IV once daily	Ceftaroline 600 mg IV every 12 hours OR Linezolid 600 mg PO/IV q12h for 6 weeks ± Rifampin 600–900 mg PO qd OR Levofloxacin 500–750 mg/day PO/IV ± Rifampin 600–900 mg PO qd
Penicillin-sensitive Streptococcus	Penicillin G 20 MU/day IV continuously or q4h for 4–6 weeks OR Ceftriaxone 1–2 g IV/IM q24h for 4–6 weeks	Cefazolin 1–2 g IV q8h for 4–6 weeks OR Vancomycin 15 mg/kg IV q12h for 4–6 weeks
Enterococcus or Streptococcus (MIC≥ 0.5 μg/mL) or Abiotrophia or Granulicatella	Ceftriaxone 1–2 g IV/IM q24h for 4–6 weeks OR Ertapenem 1 g IV q24h	Levofloxacin 500–750 mg PO qd OR Ciprofloxacin 500–750 mg PO bid for 4–6 weeks
Pseudomonas aeruginosa	Cefepime 2 g IV q12h OR Meropenem 1 g IV q8h OR Imipenem 500 mg IV q6h for 4–6 weeks	Ciprofloxacin 750 mg PO q12h OR Ceftazidime 2 g IV q8h for 4–6 weeks
Enterobacteriaceae	Ceftriaxone 1–2 g IV/IM q24h for 4–6 weeks OR Ertapenem 1 g IV q24h	Levofloxacin 500–750 mg PO qd OR Ciprofloxacin 500–750 mg PO bid for 4–6 weeks

Diabetic foot osteomyelitis

This table describes the treatment options for diabetic foot ostemyelitis.

Specific group	Diabetic Foot Osteomyelitis
	Preferred regimen	Alternative regimen
Mild to moderate infection	Clindamycin (300 to 450 mg every 6 to 8 hours) OR Linezolid (600 mg every 12 hours) OR Penicillin or cephalexin or dicloxacillin + Trimethoprim-sulfamethoxazole or doxycycline	Trimethoprim-sulfamethoxazole + Amoxicillin-clavulanate OR Clindamycin + Ciprofloxacin or levofloxacin or moxifloxacin
Severe infection ¶	Ampicillin-sulbactam (3 g every 6 hours) OR Piperacillin-tazobactam (4.5 g every 6 to 8 hours) OR Imipenem-cilastatin (500 mg every 6 hours) OR Meropenem (1 g every 8 hours) OR Ertapenem (1 g every 24 hours) OR Moxifloxacin (400 mg IV every 24 hours) If MRSA is suspected add one of the following agents Vancomycin (15 to 20 mg/kg every 8 to 12 hours) OR Linezolid (600 mg IV every 12 hours) OR Daptomycin (4 to 6 mg/kg every 24 hours)

¶ _{Severe infection defined as:}

_{Extensive infections that involve deep tissues, limb-threatening diabetic foot infections and those that are associated with systemic toxicity.}

Vertebral osteomyelitis

Pathogen directed based treatment for vertebral osteomyelitis.

Specific group		Vertebral Osteomyelitis
		Preferred regimen	Alternative regimen
Oxacillin sensitive staphylococcus aureus (OSSA) or coagulase-negative staphylococci		Nafcillin sodium or Oxacillin 1.5-2 g IV q4-6h or continuous infusion for 6 weeks OR Cefazolin 1-2 g IV q8h for 6 weeks OR Ceftriaxone 2 g IV q24h for 6 weeks	Vancomycin IV 15-20 mg/kg q12 hd for 6 weeks OR Daptomycin 6-8 mg/kg IV q24h for 6 weeks OR Linezolid 600 mg PO/IV q12h for 6 weeks OR Levofloxacin 500-750 mg PO q24h for 6 weeks OR Clindamycin IV 600-900 mg q8h for 6 weeks
Oxacillin resistant staphylococcus aureus (ORSA)		Vancomycin IV 15-20 mg/kg q12h for 6 weeks	Daptomycin 6-8 mg/kg IV q24h OR Linezolid 600 mg PO/IV q12 h OR Levofloxacin PO 500–750 mg PO q24 h + Rifampin PO 600 mg q24h for 6 weeks
β-hemolytic Streptococci		Penicillin G 20-24 million units IV q24h continuously or in 6 divided doses for 6 weeks OR Ceftriaxone 2 g IV q24h for 6 weeks	Vancomycin IV 15-20 mg/kg q12h for 6 weeks
Enterobacteriaceae		Cefepime 2 g IV q12h for 6 weeks OR Ertapenem 1 g IV q24h for 6 weeks	Ciprofloxacin 500-750 mg PO q12h or 400 mg IV q12h for 6 weeks
Pseudomonas aeruginosa		Cefepime 2 g IV q8-12h for 6 weeks OR Meropenem 1 g IV q8h for 6 weeks OR Doripenem 500 mg IV q8h for 6 weeks	Ciprofloxacin 750 mg PO q12h or 400 mg IV q8h) for 6 weeks OR Aztreonam 2 g IV q8h for 6 weeks OR Ceftazidime 2 g IV q8h for 6 weeks
Enterococcus	Penicillin susceptible	Penicillin G 20-24 million units IV q24h continuously or in 6 divided doses OR Ampicillin sodium 12 g IV q24h continuously or in 6 divided doses	Vancomycin 15-20 mg/kg IV q12h OR Daptomycin 6 mg/kg IV q24h OR Linezolid 600 mg PO or IV q12h
	Penicillin resistant	Vancomycin IV 15-20 mg/kg q12h	Daptomycin 6 mg/kg IV q24h OR Linezolid 600 mg PO or IV q12h
Propionibacterium acnes		Penicillin G 20 million units IV q24h continuously or in 6 divided doses for 6 weeks OR Ceftriaxone 2 g IV q24h for 6 weeks	Clindamycin 600-900 mg IV q8h for 6 weeks OR Vancomycin IV 15-20 mg/kg q12h for 6 weeks
Salmonella species		Ciprofloxacin PO 500 mg q12h or IV 400 mg q12h for 6-8 weeks	Ceftriaxone 2 g IV q24h for 6-8 weeks

Specific conditions

The treatment of other rare types of osteomyelitis are summarized in the table below.

Specific condition		Anti-biotic regimen
		Preferred	Alternative
Open Fracture Osteomyelitis	S. aureus or P. aeruginosa	Vancomycin 1 g IV q12h + (Ceftazidime 2 g IV q8h OR Cefepime 2 g IV q8h)	Linezolid 600 mg IV/PO bid + Ceftazidime 2 g IV q8h OR Linezolid 600 mg IV/PO bid + Cefepime 2 g IV q8h
	Gram negative bacilli	Ciprofloxacin 750 mg PO bid	Levofloxacin 750 mg PO qd
Sternal Osteomyelitis		Vancomycin 1 g IV q12h (If over 100kg, 1.5 g IV q12h)	Linezolid 600 mg PO/IV bid
Candidal Osteomyelitis		Fluconazole 400 mg/day (6 mg/kg/day) PO for 6–12 months	Anidulafungin 200 mg loading dose THEN 100 mg/day PO OR Caspofungin 70mg loading dose THEN 50 mg/day PO OR Micafungin 100 mg/day PO
Hemoglobinopathy-Associated Osteomyelitis		Ciprofloxacin 400 mg IV q12h	Levofloxacin 750 mg IV q24h