akinohanayuki ブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.

化膿性脊椎炎のメモ

先日、メーカーのweb公演を拝聴しました。

 
メーカー勉強会は、メッセージが偏るので、新人におすすめできません。私は徐々に参加が減り、2015年度は2回でした。
今回も、30回以上製品名を出して、強力宣伝でした…
 
化膿性脊椎炎は難しい感染症の1つと感じています。
 
黄色ブドウ球菌菌血症マネージメント重要ですよね。やはり、予防が大切です。
 
臨床においては、病原微生物の検出まで、抗菌薬投与を待てるのかどうか、しばしば主治医との協議で悩むポイントです。また、投与期間の長さも悩みます。
 
それでは、UpToDate と ガイドラインなどから復習です。

 

Vertebral osteomyelitis occurs by three basic routes: hematogenous spread from a distant site or focus of infection (this is the most common mechanism), direct inoculation from trauma or spinal surgery, and contiguous spread from adjacent soft tissue infection.
 
The most important infecting organism in vertebral osteomyelitis is Staphylococcus aureus, accounting for more than 50 percent of cases. Other pathogens include enteric gram-negative bacilli, Candida spp, Pseudomonas aeruginosa, groups B and G streptococci, Brucella spp, and Mycobacterium tuberculosis. 
 
The major clinical manifestation of vertebral osteomyelitis is back or neck pain, with or without fever. The most common clinical finding is local tenderness to percussion over the involved posterior spinous processes. The most common laboratory abnormalities are elevated erythrocyte sedimentation rate and C-reactive protein. 
 
Vertebral osteomyelitis should be suspected on the basis of clinical features and radiographic studies (magnetic resonance imaging is the most sensitive radiographic technique) and confirmed by biopsy of the infected intervertebral disc space or vertebral bone. Blood cultures are positive in up to 50 to 70 percent of patients; a biopsy may not be necessary in patients with clinical and radiographic findings typical of vertebral osteomyelitis and positive blood cultures with a likely pathogen.
 
Every effort should be made to identify the pathogen(s) before starting antimicrobial treatment. In patients with suspected vertebral osteomyelitis, we favor the clinical approach described above and summarized in the Algorithm. Evaluation for concurrent infectious endocarditis may be warranted in select patients. 
 
Most cases of vertebral osteomyelitis respond to antimicrobial therapy. Surgery is necessary in a minority of patients with vertebral osteomyelitis; prompt surgery is warranted for patients with focal neurologic deficits, epidural or paravertebral abscess, and/or cord compression. 
 
If possible, antimicrobial therapy should be withheld until a microbiologic diagnosis is confirmed. Clinical exceptions include neurologic compromise and sepsis; in these circumstances, empiric antibiotic therapy is warranted. Choice of antibiotic therapy should be guided by biopsy or blood culture results if available. For patients with negative culture results, empiric treatment is warranted based on the most likely organisms to cause infection. 
 
We generally treat for a minimum duration of 6 weeks. Longer therapy (up to 12 weeks) may be necessary for patients with advanced disease. 
 
TREATMENT
 
Management of vertebral osteomyelitis consists of antimicrobial therapy; in addition, evaluation for surgery is warranted for patients with neurologic deficits, radiographic evidence of epidural or paravertebral abscess, and/or cord compression (threatened or actual).
 
Antimicrobial therapy
 
Clinical approach — Selection of antimicrobial therapy should be tailored to results of biopsy or blood culture.
 
If possible, antimicrobial therapy should be withheld until a microbiologic diagnosis is confirmed. Clinical exceptions include neurologic compromise and sepsis; in these circumstances, empiric antibiotic therapy is warranted. In one retrospective study including 92 patients with vertebral osteomyelitis, administration of antibiotics prior to biopsy did not diminish the yield of culture results.
 
If blood and biopsy cultures are negative and the clinical suspicion for vertebral osteomyelitis is high based on clinical and radiographic findings, initiation of empiric therapy is warranted.
 
Pathogen-directed therapy — No randomized controlled studies have compared antibiotic regimens for vertebral osteomyelitis. Choice of antibiotic therapy should be guided by biopsy or blood culture results:
 
Staphylococcal spp – If the organism is found to be methicillin-susceptible Staphylococcus, we recommend treatment with an anti-staphylococcal penicillin such as nafcillin or oxacillin (2 g intravenously [IV] every 4 hours) or cefazolin (2 g IV every 8 hours). If the Staphylococcus is methicillin resistant or if the patient is allergic to beta-lactam antibiotics, we favor beta-lactam desensitization or treatment with vancomycin (15 to 20 mg/kg/dose every 8 to 12 hours, not to exceed 2 g per dose). We do not use ceftriaxone as an alternative to cefazolin or anti-staphylococcal penicillin in the absence of special circumstances (such as inability to give multiple daily intravenous doses).
 
Streptococcal spp – If the streptococci is fully sensitive to penicillin (minimum inhibitory concentration [MIC] <0.12 mcg/mL), we recommend treatment with either ceftriaxone (1 to 2 g IV every 24 hours) or penicillin G (12 to 18 million U/day by continuous infusion or in six divided daily doses).
If the Streptococcus has intermediate susceptibility to penicillin (MIC between 0.12 and 0.5 mcg/mL), we typically treat with ceftriaxone or higher doses of penicillin (24 million U/day per continuous infusion or in six divided daily doses). Patients with intermediate or fully resistant streptococci should be treated in collaboration with an infectious disease specialist. Specialized in vitro testing may be needed to select an appropriate antibiotic regimen for infections caused by fully resistant streptococci.
 
Gram-negative bacilli – Choice of a specific agent for empiric therapy of gram-negative bacilli should be based on knowledge of the prevailing pathogens (and susceptibility patterns) within the healthcare setting. Initial treatment with one of the following is appropriate:
Third-generation cephalosporin (ceftriaxone 1 to 2 g IV daily or ceftazidime 2 g IV every 8 hours or cefotaxime 2 g IV every 6 hours)
Fourth-generation cephalosporin (cefepime 2 g IV every 12 hours)
Fluoroquinolone (ciprofloxacin 400 mg IV every 12 hours or 500 to 750 mg orally every 12 hours)
 
Propionibacterium acnes – For treatment of infection due to P. acnes, we favor penicillin (20 to 24 million units IV daily by continuous infusion or in six divided doses) or vancomycin (15 to 20 mg/kg/dose every 8 to 12 hours, not to exceed 2 g per dose).
 
Empiric therapy 
 
Patients with negative Gram stain and culture results should be treated with an antimicrobial regimen with activity against the common causes of vertebral osteomyelitis, including staphylococci, streptococci, and gram-negative bacilli.
 
An appropriate empiric regimen consists of vancomycin (15 to 20 mg/kg/dose every 8 to 12 hours, not to exceed 2 g per dose) plus one of the following: cefotaxime (2 g IV every 6 hours), ceftazidime (1 to 2 g IV every 8 to 12 hours), ceftriaxone (1 to 2 g IV daily), cefepime (2 g IV every 12 hours), or ciprofloxacin (400 mg IV every 12 hours or 500 to 750 mg orally twice daily).
 
Anaerobes are uncommon pathogens in patients with vertebral osteomyelitis, and we do not routinely add anaerobic coverage to initial empiric therapy. Such coverage is warranted if clinical features suggest that the infection may be due to anaerobic organisms (such as in the setting of a concomitant intraabdominal abscess) or if the Gram stain is positive but aerobic cultures are negative. In such cases, metronidazole (500 mg IV every six hours) may be added to the above regimen.
 
If empiric therapy does not result in objective clinical improvement (decreasing inflammatory markers, resolving fever and back discomfort) in three to four weeks, a repeat percutaneous needle biopsy or open surgical biopsy should be performed.
 
Duration of therapy
 
We routinely treat for a minimum of six weeks. Longer therapy (up to 12 weeks) may be necessary for patients with advanced disease as manifested by extensive bone destruction and/or paravertebral infection. An extended duration of therapy may be appropriate in the setting of infection due to drug-resistant organisms and/or in the setting of extensive bone destruction or abscess(es).
 
The approach to duration of therapy is supported by a randomized trial including 351 patients with vertebral osteomyelitis; it demonstrated that 6 weeks of antibiotic treatment was not inferior to 12 weeks of antibiotic therapy with respect to the proportion of patients cured at one year. The number of patients with abscesses in the trial was low (19 percent) and computed tomography (CT)-guided drainage was needed in only 4 percent of cases. In addition, a short duration of intravenous therapy was administered (median 14 days); the most common oral antibiotic regimen was a fluoroquinolone with rifampin. The trial did not include patients with culture-negative infections. The most commonly isolated pathogen was S. aureus; fluoroquinolones are not ideal drugs for treatment of staphylococcal infections.
 
Most patients require completion of treatment with parenteral therapy. Completion of treatment with oral therapy following at least two weeks of parenteral therapy may be reasonable in the following circumstance
 
●The infection is uncomplicated and the patient has no significant comorbidities.
●A favorable clinical response to initial parenteral therapy is observed.
●A suitable drug with proven susceptibility to the causative organism is available.
Compliance with oral therapy can be assured or carefully monitored.
Patients with laboratory and radiographic evidence of treatment failure warrant repeat tissue biopsy (via image-guided aspiration or surgery) for microbiologic and histologic examination.
 
 
Clin Infect Dis. 2015;61(6):e26.
2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults.
 
I. When Should the Diagnosis of NVO Be Considered?
 
1. Clinicians should suspect the diagnosis of NVO in patients with new or worsening back or neck pain and fever (strong, low).
2. Clinicians should suspect the diagnosis of NVO in patients with new or worsening back or neck pain and elevated ESR or CRP (strong, low).
3. Clinicians should suspect the diagnosis of NVO in patients with new or worsening back or neck pain and bloodstream infection or infective endocarditis (strong, low).
4. Clinicians may consider the diagnosis of NVO in patients who present with fever and new neurologic symptoms with or without back pain (weak, low).
5. Clinicians may consider the diagnosis of NVO in patients who present with new localized neck or back pain, following a recent episode of Staphylococcus aureus bloodstream infection (weak, low).
 
II. What Is the Appropriate Diagnostic Evaluation of Patients With Suspected NVO?
 
6. We recommend performing a pertinent medical and motor/sensory neurologic examination in patients with suspected NVO (strong, low).
7. We recommend obtaining bacterial (aerobic and anaerobic) blood cultures (2 sets) and baseline ESR and CRP in all patients with suspected NVO (strong, low).
8. We recommend a spine MRI in patients with suspected NVO (strong, low).
9. We suggest a combination spine gallium/Tc99 bone scan, or computed tomography scan or a positron emission tomography scan in patients with suspected NVO when MRI cannot be obtained (eg, implantable cardiac devices, cochlear implants, claustrophobia, or unavailability) (weak, low).
10. We recommend obtaining blood cultures and serologic tests for Brucella species in patients with subacute NVO residing in endemic areas for brucellosis (strong, low).
11. We suggest obtaining fungal blood cultures in patients with suspected NVO and at risk for fungal infection (epidemiologic risk or host risk factors) (weak, low).
12. We suggest performing a purified protein derivative (PPD) test or obtaining an interferon-γ release assay in patients with subacute NVO and at risk for Mycobacterium tuberculosis NVO (ie, originating or residing in endemic regions or having risk factors) (weak, low).
13. In patients with suspected NVO, evaluation by an infectious disease specialist and a spine surgeon may be considered (weak, low).
 
III. When Should an Image-Guided Aspiration Biopsy or Additional Workup Be Performed in Patients With NVO?
 
14. We recommend an image-guided aspiration biopsy in patients with suspected NVO (based on clinical, laboratory, and imaging studies) when a microbiologic diagnosis for a known associated organism (S. aureus, Staphylococcus lugdunensis, and Brucella species) has not been established by blood cultures or serologic tests (strong, low).
15. We advise against performing an image-guided aspiration biopsy in patients with S. aureus, S. lugdunensis, or Brucella species bloodstream infection suspected of having NVO based on clinical, laboratory, and imaging studies (strong, low).
16. We advise against performing an image-guided aspiration biopsy in patients with suspected subacute NVO (high endemic setting) and strongly positive Brucella serology (strong, low).
 
IV. How Long Should Antimicrobial Therapy Be Withheld Prior to an Image-Guided Diagnostic Aspiration Biopsy in Patients With Suspected NVO?
 
17. In patients with neurologic compromise with or without impending sepsis or hemodynamic instability, we recommend immediate surgical intervention and initiation of empiric antimicrobial therapy (strong, low).
 
V. When Is It Appropriate to Send Fungal, Mycobacterial, or Brucellar Cultures or Other Specialized Testing Following an Image-Guided Aspiration Biopsy in Patients With Suspected NVO?
 
18. We suggest the addition of fungal, mycobacterial, or brucellar cultures on image-guided biopsy and aspiration specimens in patients with suspected NVO if epidemiologic, host risk factors, or characteristic radiologic clues are present (weak, low).
19. We suggest the addition of fungal and mycobacterial cultures and bacterial nucleic acid amplification testing to appropriately stored specimens if aerobic and anaerobic bacterial cultures reveal no growth in patients with suspected NVO (weak, low).
 
VI. When Is It Appropriate to Send the Specimens for Pathologic Examination Following an Image-Guided Aspiration Biopsy in Patients With Suspected NVO?
 
20. If adequate tissue can be safely obtained, pathologic specimens should be sent from all patients to help confirm a diagnosis of NVO and guide further diagnostic testing, especially in the setting of negative cultures (strong, low).
 
VII. What Is the Preferred Next Step in Patients With Nondiagnostic Image-Guided Aspiration Biopsy and Suspected NVO?
 
21. In the absence of concomitant bloodstream infection, we recommend obtaining a second aspiration biopsy in patients with suspected NVO in whom the original image-guided aspiration biopsy specimen grew a skin contaminant (coagulase-negative staphylococci [except S. lugdunensis], Propionibacterium species, or diphtheroids) (strong, low).
22. In patients with a nondiagnostic first image-guided aspiration biopsy and suspected NVO, further testing should be done to exclude difficult-to-grow organisms (eg, anaerobes, fungi, Brucella species, or mycobacteria) (strong, low).
23. In patients with suspected NVO and a nondiagnostic image-guided aspiration biopsy and laboratory workup, we suggest either repeating a second image-guided aspiration biopsy, performing percutaneous endoscopic discectomy and drainage (PEDD), or proceeding with an open excisional biopsy (weak, low).
 
RCT
 
Lancet 2015 Mar 7; 385(9971):875-82.
Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial.
  • 6 weeks of antibiotic treatment is not inferior to 12 weeks of antibiotic treatment with respect to the proportion of patients with pyogenic vertebral osteomyelitis cured at 1 year, which suggests that the standard antibiotic treatment duration for patients with this disease could be reduced to 6 weeks.
 
J. Antimicrob. Chemother. 2008 Jan; 61(1):177-82.
Outcomes with daptomycin versus standard therapy for osteoarticular infections associated with Staphylococcus aureus bacteraemia.
  • Daptomycin may be considered an alternative to standard therapy in the treatment of patients with complicated SAB and OAI.
 
その他
 
Clin Infect Dis. 2011;52(7):867.
The impact of prebiopsy antibiotics on pathogen recovery in hematogenous vertebral osteomyelitis.
  • Patients who underwent biopsy were more likely to have weakness (53 [58%]biopsy vs 15 [26%]no biopsy; P<.001) and sensory loss (27 [29%]vs 6 [10%]; P=.006), but were less likely to have a positive blood culture result (28 [30%]vs 30 [52%]; P=.01). 

BMC Infect Dis. 2014;14:226. Epub 2014 4 27.
Is switching to an oral antibiotic regimen safe after 2 weeks of intravenous treatment for primary bacterial vertebral osteomyelitis?
  • A lower CRP at 2 weeks was the only independent predictor for switch to oral therapy (OR 0.7, 95% confidence interval 0.5-0.9,p = 0.041, per 10 mg/l increase). 

Clin. Infect. Dis. 2016 Feb 24.
Optimal Duration of Antibiotic Therapy in Patients With Hematogenous Vertebral Osteomyelitis at Low Risk and High Risk of Recurrence.
  • Antibiotic therapy of prolonged duration (≥8 weeks) should be given to patients with HVO at high risk of recurrence. For low-risk patients, a shorter duration (6-8 weeks) of pathogen-directed antibiotic therapy may be sufficient.