Osteomyelitis

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%)