Osteomyelitis¶

Chapter 136 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Bacterial · Chapter 136

Key Clinical Points¶

Osteomyelitis is an infection of bone via hematogenous spread, contiguous spread, or vascular insufficiency.
Vertebral osteomyelitis is the most common manifestation of hematogenous bone infection in adults.
Diagnosis relies on high-sensitivity markers: ESR (98%) and CRP (100%).
MRI is the gold standard for diagnosing vertebral osteomyelitis and identifying complications like epidural abscesses.
Blood cultures have a 30–78% yield; negative results do not rule out infection if clinical suspicion is high.
Implant-associated infections require surgical management, often involving removal and prolonged antibiotics (3 months).
Acute hematogenous osteomyelitis typically requires 4–6 weeks of antibiotics without surgery in uncomplicated cases.
Periprosthetic joint infection (PJI) is categorized as early (<2 years) or late (≥2 years).
S. aureus is the primary pathogen in acute hematogenous infections and PJI; coagulase-negative staphylococci are common in implant-associated cases.
Epidural abscesses occur in 15–20% of vertebral osteomyelitis cases, potentially causing neurologic deficits.
Tuberculosis is a significant cause of subacute/chronic vertebral osteomyelitis in endemic regions (Africa, Asia, Middle East).
Oral antibiotics are noninferior to IV therapy for vertebral osteomyelitis if bioavailability >90% and patient has normal intestinal function.

DEFINITION & CLASSIFICATION¶

• Definition (Harrison's 22e): infection of bone caused by various microorganisms arriving via hematogenous spread, contiguous spread, or vascular insufficiency. • Pathogenesis-based Classification: ◦ Hematogenous: Common in children (long bones) and adults (vertebral column). ◦ Contiguous: Follows trauma/surgery; common in long bones. ◦ Vascular Insufficiency: Often follows diabetic foot syndrome. • Duration-based Classification: ◦ Acute: Short duration. ◦ Subacute/Chronic: Weeks to months; may recur after >70 years of remission. • Location-based Classification: ◦ Long bones, Vertebral column, Periarticular bones. • Foreign Material Status: ◦ Native bone vs. Implant-associated (requires multidisciplinary management). • Surgical Staging: ◦ Cierny-Mader system: Used by trauma surgeons to stratify long-bone osteomyelitis for surgical management.

EPIDEMIOLOGY¶

• Vertebral Osteomyelitis: ◦ More common in males (1.5:1 ratio). ◦ Incidence increased from 2.2 to 5.8 cases/100,000 person-years (1995–2008). ◦ Age-dependent: Men ≥70 years have 6x higher incidence than those <70. • Healthcare-Associated Infections: ◦ Increasing due to comorbidities and invasive interventions. ◦ Most adult long-bone cases are posttraumatic or postsurgical. • Fracture-related Infection: ◦ Risk: <1% for closed fractures vs. 2–30% for open fractures. • Tuberculous Osteomyelitis: ◦ Rare in North America/Western Europe; common in India, Indonesia, China.

Risk Factors¶

• Non-modifiable: Age ≥70 years, Male sex, Comorbidities (Diabetes, HIV). • Modifiable: IV drug use, Obesity, Chronic renal failure, Emergency surgery, Bilateral internal mammary artery grafts. • Implant-related: Open vs. closed fracture type, Time between injury and admission.

ETIOLOGY & PATHOPHYSIOLOGY¶

• Vertebral Osteomyelitis Pathogenesis: ◦ Microorganisms enter via segmental arterial circulation into the disk or retrograde through prevertebral venous plexus. ◦ Only ~50% of cases have identifiable primary foci (e.g., urinary tract, skin/soft tissue, catheters, endocardium). • Long-Bone Osteomyelitis Pathogenesis: ◦ Children: Primarily hematogenous seeding. ◦ Adults: Exogenous contamination (open fractures) or perioperative contamination. • Implant Dynamics: ◦ Foreign devices coated with fibronectin promote staphylococcal biofilm formation. ◦ Risk of recurrence in chronic cases after >70 years of remission.

CLINICAL FEATURES¶

• Vertebral Osteomyelitis: ◦ Back pain: Primary symptom (>85%). ◦ Fever: Only ~50% develop fever >38°C. ◦ Location: Cervical (10%), Thoracic (30%), Lumbar (60%). ◦ Neurologic deficits: 1/3 of cases; caused by spinal epidural abscesses. ◦ Progression: Severe localized back pain → radicular pain, reflex changes, motor weakness, bowel/bladder dysfunction, paralysis. • Long-Bone Osteomyelitis: ◦ Symptoms: Pain and low-grade fever. ◦ Sepsis/Local signs: Erythema/swelling in 10–12% of cases. ◦ Brodie's abscess (tibia/femur): Pain (98%), swelling (53%). ◦ Timing: Median 3 months from symptoms to diagnosis. • Periprosthetic Joint Infection (PJI): ◦ Early (<2 years): Chronic pain, nonspecific symptoms; local signs rare in hip, frequent in knee. ◦ Late (>2 years): Implant loosening, effusion, or sinus tracts; fever is rare after initial bacteremia.

DIFFERENTIAL DIAGNOSIS¶

• Vertebral Osteomyelitis DDx: ◦ Pyelonephritis, Pancreatitis, Viral syndromes. ◦ Noninfectious: Osteoporotic fracture, Seronegative spondylitis (ankylosing spondylitis, psoriasis, reactive arthritis, enteropathic arthritis), Spinal stenosis, Erosive osteochondrosis, Septic bone necrosis, Gouty spondylodiskitis, Andersson lesions in ankylosing spondylitis, Bone metastases, Herniated disk. • Long-Bone Osteomyelitis DDx: ◦ Fracture healing, Soft tissue injury, Bone tumor, Hematoma.

DIAGNOSTIC APPROACH¶

Clinical Suspicion: Identify back pain, fever, and risk factors.
Laboratory Testing: ◦ Leukocytosis (sensitivity 65%) and Neutrophilia (40%). ◦ ESR (98% sensitivity) and CRP (100% sensitivity) to exclude infection. ◦ Blood cultures: Yield 30–78%; note that pre-treatment reduces yield.
Imaging: ◦ Plain radiography: First step; low sensitivity in acute cases but useful for alternative diagnoses. ◦ MRI: Gold standard; detects pyogenic complications; essential for rapid assessment of neurologic impairment. ◦ CT: Less sensitive than MRI; used to guide biopsy or detect bone necrosis (sequestra). ◦ PET/CT (18F-FDG): High accuracy; use if MRI is contraindicated, for implants, or multiple foci. ◦ Three-phase bone scan: Highly sensitive but not specific; not useful in first year post-implantation. ◦ SPECT/CT: Preferred for osteomyelitis >1 year duration.
Synovial Fluid Analysis (for PJI): ◦ Knee: ≥ 1700 leukocytes/μL. ◦ Hip: ≥ 4200 leukocytes/μL. ◦ α-Defensin: Highly specific but not for screening.
Tissue Acquisition: ◦ CT-guided or open biopsy if cultures are negative or diagnosis is unclear. ◦ Obtain 3–6 tissue samples for culture (aerobic, anaerobic, fungal, mycobacteria, brucella) and histopathology.
Advanced Techniques: ◦ Sonication of implant material followed by PCR/culture to detect biofilm-related pathogens.
Decision Logic: Clinical suspicion → Lab tests → Imaging → Biopsy (if needed) → Histopathology/Culture → Non-culture techniques (PCR, Metagenomics) → Surgical exploration.

MANAGEMENT & TREATMENT¶

Initial Strategy: Determine duration (acute vs. chronic), presence of implants, and clinical stability.
Vertebral Osteomyelitis Treatment: ◦ Duration: 6 weeks for acute; 3 months for implant-associated. ◦ Route: Oral noninferior to IV if bioavailability >90% and patient has normal intestinal function. ◦ Table 1 (No Implants) Reference: → Methicillin-susceptible Staph: Nafcillin or oxacillinc (2 g IV q6h) + Rifampin (300–450 mg PO q12h) + Levofloxacin (750 mg PO q24h or 500 mg PO q12h). → Methicillin-resistant Staph: Vancomycin (15 mg/kg IV q12h) or daptomycin (8–10 mg/kg IV q24h) + Rifampin (300–450 mg PO q12h) + Levofloxacin (750 mg PO q24h or 500 mg PO q12h) OR TMP-SMX (1 double-strength tablet PO q8h) OR fusidic acid (500 mg PO q8h). → Enterobacteriaceae: Ciprofloxacin (750 mg PO q24h) or Imipenem (500 mg IV q6h) or meropenem (1–2g IV q8h). → Anaerobes: Clindamycin (600 mg IV q6–8h) for 2–4 weeks, followed by Clindamycini (300 mg PO q6h).
Long-Bone Osteomyelitis Treatment: ◦ Duration: 4–6 weeks for acute cases. ◦ Surgery: Required for chronic/recurrent cases or when sequestra/implants present. ◦ No surgery: If uncomplicated, good soft tissue, and no implants.
Periprosthetic Joint Infection (PJI) Treatment: ◦ Early (<2 years): Fluoroquinolone + rifampin for 3 months. ◦ Late (>2 years): Implant removal + 6-week antibiotics. ◦ Non-removable: Long-term suppressive oral therapy if removal not feasible (monitor CRP). ◦ Table 2 (With Implants) Reference: → Methicillin-susceptible Staph: Rifampin (450 mg PO/IV q12h) + Nafcillin or oxacillinc (2 g IV q6h). → Methicillin-resistant Staph: Rifampin (450 mg PO/IV q12h) + Vancomycin (15 mg/kg IV q12h) or daptomycin (8–10 mg/kg IV q24h). → Streptococcus spp.: Penicillin G (18–24 million units/d IV in 6 divided doses) or ceftriaxone (2 g IV q24h) for 4 weeks, followed by Amoxicillin (750–1000 mg PO q6–8h) or clindamycin (1200–1350 mg/d PO in 3 or 4 divided doses). → Cutibacterium spp.: Penicillin G (18–24 million units/d IV in 6 divided doses) or clindamycin (600–900 mg IV q8h) for 2–4 weeks, followed by Amoxicillin (750–1000 mg PO q6–8h) or clindamycin (1200–1350 mg/d PO in 3 or 4 divided doses). → Mixed bacteria: Ampicillin-sulbactam (3 g IV q6h) or amoxicillin-clavulanatel (2.2 g IV q6h) or piperacillin-tazobactam (4.5 g IV q8h) or imipenem (500 mg IV q6h) or meropenem (1–2 g IV q8h) for 2–4 weeks.

COMPLICATIONS & PROGNOSIS¶

• Vertebral Osteomyelitis Complications: ◦ Epidural abscess: 15–20% of cases. ◦ Neurologic deficits: Radiculopathy, weakness, sensory loss. ◦ Chronic infection: Sinus tracts, recurrent episodes. • Long-Bone Osteomyelitis Complications: ◦ Chronic infection: Recurrent episodes, sinus tracts. ◦ Implant failure: Loosening, infection persistence. ◦ Amputation risk: In severe diabetic foot infections.

SPECIAL POPULATIONS¶

• Tuberculous Osteomyelitis: ◦ Requires anti-TB therapy (6–12 months). ◦ High suspicion in India, Indonesia, China. • Sternal Osteomyelitis: ◦ Common after cardiac surgery; management includes debridement and 6–12 weeks of antibiotics; remove implant if infected.

KEY PEARLS & HIGH-YIELD POINTS¶

• Pearl 1: MRI is the gold standard for diagnosing vertebral osteomyelitis. • Pearl 2: Oral antibiotics are noninferior to IV in vertebral osteomyelitis if bioavailability >90% and patient has normal intestinal function. • Pearl 3: Blood cultures have low yield (30–78%) after antibiotic pretreatment. • Trap 1: Negative blood cultures do not rule out infection; biopsy is required. • Trap 2: Chronic PJI may mimic degenerative joint disease without inflammatory signs. • Pearl 4: SPECT/CT is useful for chronic osteomyelitis >1 year's duration.

Reference Tables¶

TABLE 136-1 Antibiotic Therapy for Osteomyelitis in Adults without Implants a MICROORGANISM Staphylococcus spp.¶

Harrison's 22e, p.1064

MICROORGANISM	ANTIMICROBIAL AGENT (DOSE,b ROUTE)
Staphylococcus spp.
Methicillin-susceptible	Nafcillin or oxacillinc (2 g IV q6h)
	followed by
	Rifampin (300–450 mg PO q12h) plus levofloxacin (750 mg PO q24h or 500 mg PO q12h)
Methicillin-resistant	Vancomycind (15 mg/kg IV q12h) or daptomycin (8–10 mg/kg IV q24h)
	followed by
	Rifampin (300–450 mg PO q12h)
	plus
	Levofloxacin (750 mg PO q24h or 500 mg PO q12h) or TMP-SMXe (1 double-strength tablet PO q8h) or fusidic acid (500 mg PO q8h)
Enterobacteriaceae Quinolone-susceptible Quinolone-resistantf	Ciprofloxacin (750 mg PO q24h) Imipenem (500 mg IV q6h) or meropenem (1–2g IV q8h)
Anaerobes	Clindamycin (600 mg IV q6–8h) for 2–4 weeks
	followed by
	Clindamycini (300 mg PO q6h)

TABLE 136-2 Antibiotic Therapy for Osteomyelitis Associated with Orthopedic Devices MICROORGANISM Staphylococcus spp.¶

Harrison's 22e, p.1065

MICROORGANISM	ANTIMICROBIAL AGENTa (DOSE, ROUTE)
Staphylococcus spp.	Recommendation for initial treatment phase (2 weeks with implant)
Methicillin-susceptible	Rifampin (450 mg PO/IV q12hb)
	plus
	Nafcillin or oxacillinc (2 g IV q6h)
Methicillin-resistant	Rifampin (450 mg PO/IV q12hb)
	plus
	Vancomycin (15 mg/kg IV q12h) or daptomycin (8–10 mg/kg IV q24h)
Streptococcus spp.e	Penicillin Gc (18–24 million units/d IV in 6 divided doses) or ceftriaxone (2 g IV q24h) for 4 weeks
	followed by
	Amoxicillin (750–1000 mg PO q6–8h) or clindamycin (1200–1350 mg/d PO in 3 or 4 divided doses)
Enterobacteriaceae	A β-lactam selected in light of in vitro susceptibility profile for 2 weeksh
	followed by
	Ciprofloxacin (750 mg PO q12h)
Cutibacterium spp.	Penicillin Gc (18–24 million units/d IV in 6 divided doses) or clindamycin (600–900 mg IV q8h) for 2–4 weeks
	followed by
	Amoxicillin (750–1000 mg PO q6–8h) or clindamycin (1200–1350 mg/d PO in 3 or 4 divided doses)
Mixed bacteria (without methicillin-resistant staphylococci)	Ampicillin-sulbactam (3 g IV q6h) or amoxicillin-clavulanatel (2.2 g IV q6h) or piperacillin-tazobactam (4.5 g IV q8h) or imipenem (500 mg IV q6h) or meropenem (1–2 g IV q8hk) for 2–4 weeks followed by Individualized oral regimens chosen in light of antimicrobial susceptibility