Native vertebral osteomyelitis (IDSA 2015)

Berbari EF, Kanj SS, Kowalski TJ, Darouiche RO, Widmer AF, Schmitt SK, Hendershot EF, Holtom PD, Huddleston PM 3rd, Petermann GW, Osmon DR, Infectious Diseases Society of America. 2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults. Clin Infect Dis. 2015 Sep 15;61(6):e26-46. doi: 10.1093/cid/civ482.

Background

• Native vertebral osteomyelitis (NVO) is usually from hematogenous seeding

Diagnosis

Clinical Clues

• Suspect NVO in patients with new/worsening back/neck pain and any of the following:
  • Fever
  • Elevated ESR/CRP
  • Bacteremia or infective endocarditis
  • Following an episode of Staph.aureus bacteremia
• Suspect NVO in patients with new neurologic symptoms and fever, regardless of back pain

Diagnostic Approach

• Neurologic exam
• Blood cultures x2 and baseline ESR/CRP
• Blood cultures and serology for Brucella for subacute NVO where it is endemic
  • Spain and other countries of the Mediterranean basin, Latin America, the Middle East, parts of Africa, and Western Asia
• Fungal blood cultures if they are at risk
• TBST or IGRA if at risk for TB
• MRI spine as first-line diagnostic of choice
  • Gallium/Tc99 bone scan, of CT, or PET are alternatives
• Consider involving surgery

Biopsy

• Biopsy not needed if blood cultures grow S. aureus, Staphylococcus lugdenensis, or Brucella or Brucella serology is strongly positive
• Image-guided biopsy is recommended when a definitive organism has not been found
  • Add fungal, mycobacterial, or brucellar cultures if there is suspicion. Can also do NAAT later, if the routine bacterial cultures are negative.
  • Ideally also send a specimen for pathology
  • Do not withhold antimicrobials if there is neurologic compromised
• If the biopsy is negative or equivocal, it should be repeated
  • Test for anaerobes, fungi, Brucella, mycobacteria
  • Can consider discectomy and drainage or open excisional biopsy

Management

• If they are clinically stable with no neurologic compromise, then it is reasonable to withhold antimicrobials while attempting to establish a microbiological diagnosis
• Duration is at least 6 weeks of parenteral or highly bioavailable oral antimicrobial therapy
  • Duration in Brucella is at least 3 months
• Surgical intervention is recommended if there is neurologic compromise or worsening despite antimicrobials
  • This decision should not be based on worsening imaging when there is clinical improvement
• At 4 weeks, reassess clinically with a repeat ESR/CRP
  • If it has halved, that is a good prognostic sign
  • No need for routine repeat imaging

Common Parenteral Antibiotics

Microorganism	First-line	Alternatives	Comments
Staphylococcus spp, ox-susceptible	Nafcillin or oxacillin 1.5-2 g IV q4-6h or continuous, or Cefazolin 1-2 IV q8h, or Ceftriaxone 2 g IV q24h	Vanco 15-20 mg/kg IV q12h, or Dapto 6-8 mg/kg IV q24h, or Linezolid 600 mg PO/IV/iv q12h, or Levofloxacin 500-750 mg PO q24h and rifampin 600 PO mg daily, or Clindamycin 600-900 mg IV q8h	6 weeks
Staphylococcus spp, ox-resistant	Vanco 15-20 mg/kg IV q12h (consider loading dose)	Dapto 6-8 mg/kg IV q24h, or Linezolid 600 mg PO/IV q12h, or Levofloxacin 500-750 mg PO q24h and rifampin 600 mg PO daily	6 weeks
Enterococcus spp, pen-susceptible	Pen G 20-24 MU IV q24h continuous or 6 divided doses, or Ampicillin 12 g IV q24h continuous or in 6 divided doses	Vanco 15-20 mg/kg IV q12h, or Dapto 6 mg/kg IV q24h, or Linezolid 600 mg PO/IV q12h	May add aminoglycoside for 4-6 weeks if IE (shorter if merely bacteremia)
Enterococcus spp, pen-resistant	Vanco 15-20 mg/kg IV q12h	Dapto 6 mg/kg IV q24h, or Linezolid 600 mg PO/IV q12h	May add aminoglycoside for 4-6 weeks if IE (shorter if merely bacteremia)
Pseudomonas aeruginosa	Cefepime 2 g IV q8-12h, or Mero 1 g IV q8h, or Dori 500 mg IV q8h	Cipro 750 mg PO q12h, or Cipro 400 mg IV q8h, or Aztreonam 2 g IV q8h, or Ceftazidime 2 g IV q8h	6 weeks. Can consider double-coverage.
Enterobacteriaceae	Cefipime 2 g IV q12h, or Ertapenem 1 g IV q24h	Cipro 500-750 mg PO q12h, or Cipro 400 mg IV q12h	6 weeks
Beta-hemolytic streptococci	Pen G 20-24 MU IV q24h continuous or 6 divided doses, or Ceftriaxone 2 g IV q24h	Vanco 15-20 mg/kg IV q12h	6 weeks
Proprionibacterium acnes	Pen G 20 MU IV q24h continuous or in 6 divided doses, or Ceftriaxone 2 g IV q24h	Clinda 600-900 mg IV q8h, or Vanco 15-20 mg/kg IV q12h	6 weeks
Salmonella spp	Cipro 500 mg PO q12h, or Cipro 400 mg IV q12h	Ceftriaxone 2 g IV q24h	6-8 weeks

Common Highly Bioavailable Oral Antibiotics

Oral agent	Comments
Metronidazole 500 mg PO tid to qid	Can be used in NVO from Bacteroides and other susceptible anaerobes.
Moxifloxacin 400 mg PO daily	Not recommended as monomicrobial for staphylococci.
Linezolid 600 mg PO bid	Can be used in initial course of ox-resistant staphylococci if other aren't available.
Levofloxacin 500-750 mg PO daily	Not recommended as monomicrobial for staphylococci.
Ciprofloxacin 500-750 mg PO bid	Not recommended as monomicrobial for staphylococci.
TMP-SMX 1-2 DS tabs PO bid	Not recommended as monomicrobial for staphylococci. May need to monitor levels.
Clindamycin 300-450 mg PO qid	Second-line for susceptible staphylococci.
Doxycycline and rifampin	Mostly used for Brucella

Treatment Failure

• Ongoing findings at the end of therapy do not necessarily signify failure
  • This includes persistent pain, residual neurologic deficits, high ESR/CRP, and radiographic findings
• If the 4-week ESR/CRP is unchanged or increasing, that is suspicious for failure
• Repeat MRI, looking at paraspinal and epidural soft tissue changes, can be considered
• If suspicion is high enough, then repeat biopsy is indicated with histopathology