Deep spinal infection in adults
|Last review: 02/03/2012|
|Next review: 04/02/2022|
|Approved By: Improving Antimicrobial Prescribing Group|
|Copyright© Leeds Teaching Hospitals NHS Trust 2012|
This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
Guideline for management of deep spinal infection in adults
Deep spinal infection in adults
Criteria for use of guideline
Standard baseline investigations
Duration of treatment
Switch to oral agent[s]
The peripheral white blood cell count may be normal or elevated in patients with spinal infection and is therefore not particularly useful (An & Seldomridge, 2006). A full blood count [FBC] is indicated however to determine if the patient is anaemic, to ensure a normal platelet count before any biopsies or surgical intervention and to establish a baseline peripheral white blood cell count since several of the antimicrobials used in treatment can cause leukopaenia.
C-reactive protein [CRP] is a sensitive test, being raised in >90% of patients with spinal infection (Carragee et al., 1997; Rankine et al., 2004), but it is non-specific. A raised CRP provides supportive evidence of infection, rather than confirming the diagnosis, and can be used to monitor response to treatment.
Urea and electrolytes [U&E], liver function tests [LFT’s] are necessary baseline tests. Results will influence choice and dose of antimicrobials as well as fluid balance, nutritional support etc.
Blood cultures are positive in 33%-71% of cases of vertebral osteomyelitis (Digby & Kersley, 1979; Roblot et al., 2007; Tsiodras & Falagas, 2006). Because bacteria known to be common blood culture contaminants can also cause deep spinal infection [e.g. coagulase negative staphylococci and enterococci], two sets of Blood cultures are recommended prior to starting any antimicrobials. It is important to inoculate the optimal 8-10ml into each blood culture bottle.
In patient with possible endocarditis [clickable link to endocarditis guideline], three sets of Blood cultures should be taken at different times during the first 24 hours (Elliott et al., 2004). [Evidence level B].
Urinalysis is indicated at baseline because spinal infections frequently arise from a primary focus in the urinary tract (Sapico & Montgomerie, 1979). [Evidence level B.]
A urine sample should be sent for culture if dipstick is positive for leukocytes or white blood cells. [NB. Sterile pyuria should raise the possibility of mycobacterial infection but there is no need to culture urine for mycobacteria if a spinal biopsy is planned.] [Evidence level B.]
Patients with a purulent exudate at an epidural catheter exit site or site of a previously removed epidural catheter should have a sample of pus sent to microbiology in a sterile container, a pus swab is inferior to a pus sample. [Evidence level B.]
Plain chest X-ray is indicated for all patients with suspected chronic spinal infection because of the possibility of mycobacterial infection. [Evidence level B.]
Plain spinal X-rays are insensitive for the diagnosis of early spinal infection [<2 weeks symptoms] (Berbari et al., 2005). However, plain x-rays can be useful for monitoring progress in terms of bone destruction, development of deformity and bone healing. Plain spinal X-rays should be carried-out in all suspected spinal infections. [Evidence level B.]
Magnetic resonant imaging [MRI] of the spine is the radiological investigation of choice for suspected vertebral osteomyelitis but is neither 100% sensitive nor 100% specific (Tsiodras & Falagas, 2006). 2/20 radiological diagnoses of spinal infection turned out to have malignant lesions after biopsy in a recent series (Rankine et al., 2004). MRI did not exert a significant effect on outcome in one study; the explanation was delay in obtaining MRI (McHenry et al., 2002). MRI can diagnose VO early in the course of infection and may have a positive impact on outcome (Carragee, 1997b). The use of gadolinium contrast is advocated.
Radiologically-guided biopsy [closed biopsy] of suspected vertebral osteomyelitis is necessary to confirm the diagnosis because of the lack of specificity of clinical and radiological findings and frequent errors when therapy is started empirically (Berbari et al., 2005; Kumar et al., 2005; Rankine et al., 2004). Although there are MRI features considered diagnostic of mycobacterial infection, a false positive rate of 20% has been reported in a small series (Jung et al., 2004) and erroneous diagnoses of spinal tuberculosis can be made (Kumar et al., 2005). In addition, concurrent infection and neoplasia can occur as can mixed infection, such as mycobacteria with other bacterial pathogens. Closed spinal biopsy influenced treatment in 35% of cases in a recent series (Rankine et al., 2004) and may influence more cases if the use of empirical antibiotic therapy for this condition could be reduced.
[Evidence level D]
Sensitivity of open biopsy varies from 40-100% (An & Seldomridge, 2006; Rankine et al., 2004) and a second diagnostic procedure may be required. Sufficient biopsy material should be sent for microscopy, routine culture and mycobacterial culture. Contemporary molecular diagnostic techniques [e.g. 16S ribosomal DNA PCR] may be useful if routine cultures are negative but these require formal evaluation. Adequate biopsies can usually be obtained by closed, percutaneous techniques, typically under radiological guidance. By contrast, open biopsy techniques usually require general anaesthesia. Both techniques have low complication rates associated with the acquisition of tissue but to avoid any risks associated with general anaesthesia, the closed method is preferable.
Pus found at surgery [not pus swabs] should be sent to microbiology in a sterile container. [Evidence level B].
The biopsy material or pus from the spinal lesion should be sent for microbiology [microscopy, routine culture, mycobacterial culture] and histology in cases of suspected vertebral osteomyelitis. [Evidence level B].
Surgical and Other Non-Antimicrobial Management
The indication for surgical intervention fall into distinct categories.
These indications may co-exist to varying degrees. Such problems may mandate decompression and/or stabilisation. The effect of these complications varies, depending upon the spinal level [and extent] involved. In cases of early diagnosis and treatment, these complications are rare.
Stabilisation may mean nothing more than a period of bed rest or wearing an external orthosis. In some cases, decompression of pus can be via percutaneous guided drain insertion, often at the time of biopsy but neural compression by sequestered bone and/or disc will not be amenable to such treatment. However, the typical delays in diagnosis mean that in practice, many cases require urgent decompression and/or stabilization, by surgical means.
The advice of a spinal surgeon should be sought at an early stage and the role for surgery assessed on a case-by-case basis. In Leeds, cervical infections should be referred to neurosurgeons and thoracic, lumbar and sacral infections to orthopaedic spinal surgeons.
When spinal instrumentation is involved in an infective process the likelihood of relapse is high if the instrumentation is not removed (Benson et al., 1998; Hahn et al., 2005; Ho et al., 2007; Malamo-Lada et al., 1999). In one paediatric series >80% of patients who required three or more irrigation and debridement procedures [with the original instrumentation in place] were not cured until all the metalwork was removed. If spinal fusion is established, removal of infected metalwork may be possible without aggravating deformity. However, removal of instrumentation prior to spinal fusion may lead to progressive deformity. Early post operative infections [within 6 months] can be eradicated in some instances with debridement, irrigation and intravenous antimicrobial therapy.
|Empirical Antimicrobial Treatment|
The choice of antimicrobial agent[s] for treatment of VO will depend on penetration of the agent into spinal tissues, the pathogen involved, evidence from experimental animal models and clinical experience. Most human data come from observational studies and case reports rather than randomized controlled trials. The range of potential pathogens is wide and there is no single agent or simple combination of agents that could be used to empirically cover all of them; obtaining a microbiological diagnosis is therefore highly desirable.
A microbiological diagnosis enables administration of directed antimicrobial therapy, avoiding the need for broad-spectrum, potentially toxic therapeutic combinations or erroneous empirical therapy (Kumar et al., 2005; Rankine et al., 2004). In patients who have been administered antimicrobials before a spinal biopsy, a microbiological diagnosis was made in only 25% of episodes (Rankine et al., 2004), highlighting the need to withhold treatment until appropriate investigations have been carried out.
|Directed Antimicrobial Treatment (when microbiology results are known)|
Nafcillin [very similar to Flucloxacillin ] monotherapy has been compared to nafcillin plus Rifampicin in a small number of patients with chronic Staphylococcus aureus osteomyelitis (Norden et al., 1986). Combination therapy cured 8/10 [80%] while nafcillin monotherapy cured 4/8 [50%]; although not clinically significant, the study was probably underpowered and there was a definite trend in favour of combination therapy (Norden et al., 1986). Combination therapy in spinal infection has not been rigorously investigated.
In terms of newer antimicrobial agents such as Linezolid and Daptomycin , there are limited data: case reports and series describe both clinical success and failure. These agents should only be used in consultation with a Microbiologist (Hayden et al., 2005; Marty et al., 2006; Melzer et al., 2000; Rayner et al., 2004; Till et al., 2002; Vikram et al., 2005).
Suboptimal treatment can result in development of resistance to certain antimicrobials during therapy. Development of resistance to Ciprofloxacin and Rifampicin during therapy can be particularly problematic (Kragsbjerg et al., 2000).
For meticillin-susceptible staphylococci combination of intravenous Flucloxacillin 2g 6-hourly +/- oral Rifampicin * 300-600mg 12-hourly is recommended. Use regimen for meticillin-resistant staphylococci in patients with a genuine penicillin allergy or consider desensitization. [Evidence level D]
*Rifampicin should never be used alone for Staphylococcus aureus infections; isolates must be susceptible to Rifampicin ; there should be no historical or radiological features suggestive of tuberculosis. Dose variation because doses need adjustment in patients with severe renal impairment. The addition of Rifampicin is optional, no good quality clinical data supports it addition.
Treatment of enterococci with other susceptibility profiles requires discussion with a Microbiologist on a case-by-case basis. [Evidence level D]
For penicillin-susceptible streptococci [MIC<0.5] intravenous Benzyl penicillin 1.8-2.4g 4-hourly recommended. [Evidence level D]
Treatment of streptococci with other susceptibility profiles requires discussion with a Microbiologist on a case-by-case basis. [Evidence level D]
“coliforms” [e.g. Escherichia coli, Klebsiella spp., Proteus spp.]
For Amoxicillin-resistant, ciprofloxacin-susceptible isolates oral Ciprofloxacin 500-750mg 12-hourly is recommended. [Evidence level D]
Infections caused by organisms with other susceptibility profiles should be discussed with microbiology on a case-by-case basis. [Evidence level D]
Clinical cases have been treated with a variety of regimens. (Akermann, 1981; McGee-Collett & Johnston, 1991).
For ciprofloxacin-susceptible strains, oral Ciprofloxacin 500-750mg 12-hourly is recommended. [Evidence level D]
Actinomyces spp., Brucella spp. and fungal deep spinal infections are rare occurrences in Leeds and should be treated on a case-by case basis following discussion with microbiology.
2. Infected spinal instrumentation
|Duration of Treatment|
Two weeks treatment is usually ineffective in sterilizing bone in animal models. Observational data from patients indicates that short course therapy [<4 weeks] has been associated with treatment failure (Kumar et al., 2005; Sapico & Montgomerie, 1979). Six to eight weeks intravenous antimicrobial therapy [without prolonged oral antimicrobial therapy] is recommended by many authorities (Hadjpavlou et al., 2000; Musher et al., 1976; Osenbach et al., 1990). Such therapy is usually curative provided abscesses have either been drained or seen to resolve radiologically, pain at rest has significantly improved [mechanical pain may persist, depending on instability] and inflammatory markers have markedly improved (Sapico & Montgomerie, 1980). A recent comparative study of 120 episodes of VO showed that relapse was no more likely in patients treated for 6 weeks than those treated for >6 weeks (Roblot et al., 2007). Relapse of infection has been associated with draining sinuses and paravertebral abscesses and more prolonged therapy with surgical intervention may be necessary in such patients (McHenry et al., 2002).
Six weeks treatment is recommended in the first instance. If the patient is afebrile, CRP is returning to normal, paravertebral abscesses have been drained or resolved and rest pain is absent or greatly reduced, then antimicrobials can be stopped. Failure to improve according to these criteria should lead to continuation of treatment, further investigation, such as repeat imaging of the spine, and reconsideration of surgical intervention.
|Switch to oral agent(s)|
There is no evidence to support either a switch to oral antimicrobials during therapy or continuation of oral therapy after an appropriate course of intravenous treatment for the majority of situations (Sapico & Montgomerie, 1980; Sapico & Montgomerie, 1990; Sapico, 1996). In cases where the antimicrobial of choice has high oral bioavailability [such as Ciprofloxacin ], oral therapy may be appropriate. For some low virulence pathogens, such as Eikenella spp. or Kingella spp. conversion to oral therapy may be appropriate after a good clinical response to intravenous therapy. Infections caused by Mycobacterium tuberculosis, Actinomyces and Brucella spp. for which prolonged therapy is required, can be treated with oral therapy (Sapico & Montgomerie, 1980).
Switching to oral antimicrobials should be considered on a case by case basis, but is generally not recommended for Staphylococcus aureus infection or infections involving spinal metalwork. [Evidence level D].
|Please contact microbiology if the patient is not responding to the recommended antimicrobial regimens.|
Deep spinal infection
|Target patient group:||Adults|
|Target professional group(s):||Secondary Care Doctors
A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.
D. Leeds consensus.
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