- Email: [email protected]
Cervical Spine Osteomyelitis: A Systematic Review of Instrumented Fusion in the Modern Era
Original Article
Cervical Spine Osteomyelitis: A Systematic Review of Instrumented Fusion in the Modern Era Amy J. Wang1, Kevin T. Huang1, Timothy R. Smith1,2, Yi Lu1, John H. Chi1, Michael W. Groff1,2, Hasan A. Zaidi1,2
OBJECTIVE: For cases of cervical osteomyelitis that require surgery, concern has continued regarding instrumentation owing to the potential for bacterial seeding of the hardware. We performed a systematic review of the current data.
-
METHODS: A search was performed using Medline, Embase, and Ovid for articles using the keywords “cervical osteomyelitis/spondylodiscitis” and “fusion” or “instrumentation” reported from 1980 to 2017. Prospective or retrospective studies describing ‡2 patients with cervical osteomyelitis were included in the analysis; non-English reports were excluded. Individual patients were excluded from the final analysis if they had previously undergone spinal instrumentation.
complications were comparable to those of elective cervical spine procedures. These results suggest that surgical intervention with instrumentation is a safe treatment option for patients with cervical spine osteomyelitis.
-
RESULTS: A total of 239 patients from 24 studies met our criteria. Surgical approaches were classified as anterioronly, combined anteroposterior, and posterior-only for 64.8%, 31.9%, and 3.3% of the patients respectively. Of the patients treated using an anterior-only approach, 76.5% had received anterior plating and 85.3%, a cage or spacer implants. Of the patients who had undergone combined approaches, 85.1% underwent circumferential fixation and 14.9%, anterior debridement with posterior instrumentation. The follow-up period ranged from 6 weeks to 11 years (mean, 31.0 months). All the studies reporting the fusion rates, except for 1, reported a 100% fusion rate. The reported rates of pain improvement and neurologic recovery were favorable. The incidence of hardware failure and wound complications was 4.6% and 4.0%, respectively.
-
CONCLUSIONS: Despite placing instrumentation during active infection, the rates of hardware failure and wound
-
Key words - Cervical osteomyelitis - Cervical spondylodiscitis - Instrumented fusion Abbreviations and Acronyms ASIA: American Spinal Injury Association MRSA: Methicillin-resistant Staphylococcus aureus VAS: Visual analog scale
INTRODUCTION
C
ervical spine infections necessitate urgent treatment owing to the potential for severe neurologic complications and compromise of the integrity of the vertebral column. Compared with the thoracic and lumbar regions, the cervical spine permits a greater range of motion and the cervical spinal cord occupies a larger portion of the canal. These characteristics allow spondylodiscitis of the cervical spine to progress more rapidly and result in catastrophic neurological deficits.1,2 One retrospective study observed significantly greater rates of neurological involvement (68.4% vs. 41%) and mortality (21.2% vs. 3.6%) in patients with cervical spine pyogenic infections compared with patients with thoracolumbar infections.2 The incidence of vertebral osteomyelitis throughout the spine has been steadily increasing. In the United States, 1 population study estimated an incidence of 4.7 cases per 100,000 persons annually from 2000 to 2009, an increase from 0.5 cases per 100,000 persons annually from 1969 to 1979.3 Recent studies from Denmark and England have reported similar numbers and trends.4,5 Of these vertebral osteomyelitis cases, cervical spine osteomyelitis represents an estimated 3%e11%.6,7 Despite the relative rarity of cervical spine infections, the potentially devastating consequences, together with the increasing incidence of the disease, demonstrate a pressing need for determining optimal management.
From the 1Department of Neurosurgery and 2Computational Neuroscience Outcomes Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA To whom correspondence should be addressed: Hasan A. Zaidi, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.08.129 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Published by Elsevier Inc.
WORLD NEUROSURGERY -: e1-e11, - 2018
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ORIGINAL ARTICLE AMY J. WANG ET AL.
CERVICAL SPINE OSTEOMYELITIS AND INSTRUMENTED FUSION
Although the preferred treatment of cervical osteomyelitis is medical, surgical treatment is indicated for cases in which signs of biomechanical instability or neurologic compromise are present, or when the diagnosis needs to be established. Surgical treatment of cervical osteomyelitis involves debridement with or without instrumented fusion, using an anterior, a posterior, or a combined approach. Instrumentation is thought to improve the fusion rates and is routinely used to aid in fusion in noninfectious cases. However, because of concern for bacterial seeding on the hardware after placement of foreign materials in an active infection, the safety and efficacy of instrumentation for cervical spine infections continues to be debated. The existing data on the surgical management of cervical spine infections consist mostly of small, institutional series reporting heterogeneous patient groups. Moreover, to the best of our knowledge, more than 1 decade has elapsed since the most recent reviews of the subject, which had their own limitations in scope.6,8 Thus, we performed a systematic review of the current data focusing on patients with pyogenic cervical osteomyelitis or spondylodiscitis who underwent instrumented fusion. METHODS The systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.9 A search was conducted using Medline, Embase, and Ovid databases for articles with the keywords (“cervical osteomyelitis” OR “cervical spondylodiscitis”) AND (“fusion” OR “instrumentation”), reported from January 1980 to October 2017. Original, peer-reviewed, prospective, or retrospective studies with 2 cases of cervical spine infection were included in an initial screen. Case reports and other single-patient publications were excluded to reduce the effect of publication bias of unusual or nonrepresentative cases. Other exclusion criteria consisted of nonEnglish manuscripts and nonoperative series. If >1 publication had reported on the same patient cohort, the publication reporting the most comprehensive and relevant clinical data was included in the final analysis. The resulting articles were reviewed by 2 independent investigators (A.J.W. and K.T.H). Within each article, the patients were included in the final analysis only if they had undergone spinal instrumentation for cervical osteomyelitis or spondylodiscitis. The patients were excluded if their infection had developed from a complication of an index cervical spinal surgery or if they had been treated with noninstrumented fusion or debridement and/or decompression alone. Patients with fungal infections, because they represented a cohort with separate risk factors, comorbidities, pathophysiology, and treatment paradigms, were not included in the present study. Publications that had aggregated clinical data for a heterogeneous patient cohort such that it prevented isolation of data regarding the patients of interest, the article was removed from the analysis. If the 2 investigators disagreed on whether an article met the inclusion criteria, a third investigator (H.A.Z.) joined the discussion to reach a group consensus. We then extracted the following data from each article: study design, study country of origin, total number of patients meeting the criteria, risk factors and comorbidities, surgical approaches,
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instrumentation types, microbiology, length of antibiotic treatment, follow-up duration, pain and neurologic outcomes and the assessment tools used, fusion rates, incidence of hardware failure, and incidence of wound complication. Hardware failure was defined as screw loosening, screw pull-out, or graft subsidence. Wound complications were defined as reoperation for wound infection and/or removal of hardware because of persistent infection. A total of 309 articles were identified through the database searches. After filtering for English-language manuscripts, human subjects, and publication dates from January 1980 to October 2017, 183 unique articles remained available for title and abstract screening. Another 139 records were excluded for the following reasons: not relevant to cervical spine infection and instrumentation (n ¼ 69), individual case reports (n ¼ 51), series containing only 1 patient meeting the criteria (n ¼ 13), and review articles (n ¼ 6). The 2 investigators reviewed 44 full-text articles, of which 16 were eliminated because they had aggregated the clinical data for patients who did not meet our criteria. Another 3 were eliminated because they had included a cohort of patients who had also been included in another article. A total of 24 peer-reviewed journal articles were included in the final analysis: 18 retrospective series,1,10-26 5 case series,27-31 and 1 prospective cohort study32 (Figure 1). RESULTS Baseline Characteristics A total of 239 patients from 24 articles were included in the present study. The countries of origin were the United States,6,12,13,15,18,19,24,27,30,31 Germany,11,17,21,23,32 China,10,28 Korea,20 Taiwan,22 Japan,26 Greece,14 the United Kingdom,16 the Czech Republic,29 and Switzerland.1 All 239 patients had undergone instrumented fusion as part of their surgery. The male/female ratio was 1.8:1 (92 males [64.3%]; 51 females [35.7%]; 20 of 24 studies). The mean age across the included studies ranged from 49 to 84 years, and the mean age of the individual patients was 56.7 years (18 of 24 studies). Comorbidity data were only available for 14 of the 24 studies. The most common comorbidities were diabetes mellitus (n ¼ 26), intravenous drug use (n ¼ 23), and alcohol abuse (n ¼ 16). Other reported comorbidities included renal disease (n ¼ 8), heart disease (n ¼ 7), malignancy (n ¼ 5), remote infection (n ¼ 7, including endocarditis, n ¼ 1), hypertension (n ¼ 5), previous neck radiation (n ¼ 4), iatrogenic immunosuppression (n ¼ 1), and human immunodeficiency virus infection (n ¼ 1). Surgical Approach Regarding the surgical management, 136 patients (64.8%) underwent treatment by an anterior approach alone, 7 (3.3%) by a posterior approach alone, and 67 (31.9%) by a combined approach (all percentages computed from 210 patients from 23 of the 24 studies). For the remaining 29 patients, the surgical approach for placement of instrumentation was not specified.19 Of the 136 patients treated by an anterior-only approach, 104 (76.5%) were documented as having received anterior plating and 116 (85.3%) had received cage or spacer implants. Of the 67 patients who had undergone combined anterior and posterior approaches, 57 (85.1%) had undergone circumferential fixation, and 10 (14.9%) had undergone anterior debridement but with instrumentation
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.08.129
ORIGINAL ARTICLE AMY J. WANG ET AL.
CERVICAL SPINE OSTEOMYELITIS AND INSTRUMENTED FUSION
Figure 1. Flow diagram depicting study selection. C-spine, cervical spine.
from the posterior approach alone (including 6 who had undergone a transoral approach; (Table 1). Only 8 of 24 articles had reported definitively on which patients had undergone corpectomies.11,15,17,18,21,22,24,26 Of these studies, the rate of receiving any corpectomy (single vs. multilevel, not always specified) ranged from 13% to 100%, with several smaller series reporting that 100% of their patients had undergone corpectomies.15,17,18,24,26 However, most of these studies had not quantified the degree of bony debridement. Additionally, we did find evidence that the surgical approach differed by geographic region. When divided by continent, 52 patients (94.5%) in the Asian studies had undergone surgery with an anterior approach alone compared with 35 (49.3%) in the American cohort and 49 (58.3%) in the European cohort, with the vast majority of the rest receiving combined anteroposterior surgical approaches (n ¼ 30 [42.3%] in the U.S. group, n ¼ 35 [41.7%] in the European group, and n ¼ 2 [3.6%] in the Asian group). This difference was statistically significant when comparing the
WORLD NEUROSURGERY -: e1-e11, - 2018
surgical approach between patients from Asian and non-Asian countries of origin (P < 0.0001, c2 test). Microbiology Identified and Antibiotic Therapy We were able to extract microbiological data for our patients of interest from 17 of the 24 articles (Table 2). Of the 17 studies that reported culture data, 117 of 137 patients (85.4%) had organisms identified. Of these 117 patients, 115 (98.3%) had a single definitive organism identified. Also, for these 117 patients, Staphylococcus aureus was the most common causative agent, isolated in 79 of the patients (67.5%). Other etiologies included Staphylococcus epidermidis (n ¼ 7; 6.0%), Mycobacterium tuberculosis (n ¼ 7; 6.0%), Pseudomonas aeruginosa (n ¼ 5; 4.3%), Escherichia coli (n ¼ 5; 4.3%), Klebsiella species (n ¼ 2; 1.7%), polymicrobial (n ¼ 2; 1.7%), and various Streptococcus species (n ¼ 4; 3.4%). Within the S. aureus group, 44.0% of the cases with antibioticsensitivity data available were attributed to methicillin-resistant S. aureus (MRSA; n ¼ 11 of 25 patients; 3 studies reporting).
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Year
Country
Patients Meeting Criteria (n)
2017
China
14
14
14
14
0
0
0
0
D’Souza et al.
2016
USA
4
1
1
0
0
3
0
3
28
Zhang et al.
2016
China
24
24
24
24
0
0
0
0
Bydon et al.19
2014
USA
29*
0
0
0
0
0
0
0
Hahn et al.
2014
South Korea
9
6
6
0
1
2
0
2
Özkan et al.21
2014
Germany
18
16
16
13
0
2
1
1
2013
Taiwan
6
6
6
6
0
0
0
0
Shousha et al.
2012
Germany
29
17
17
5
0
12
2
10
Rayes et al.12
2010
USA
26
24
4
24
1
1
0
1
2010
Germany
4
4
4
0
0
0
0
0
Investigator Li et al.10 27
20
Tsai et al.22 11
23
Walter et al. 24
Anterior Approach Alone (n)
Cage or Spacer Implants (n)
Anterior Plating (n)
Posterior Approach Alone (n)
Combined Approach (n)
Anterior Debridement and Posterior Fixation (n)
Circumferential Fixation (n)
2009
USA
6
1
1
0
0
5
0
5
Mondorf et al.32
2009
Germany
5
5
5
0
0
0
0
0
Acosta et al.25
2008
USA
4
0
0
0
0
4
0
4
Suess et al.17
2007
Germany
3
3
3
3
0
0
0
0
2006
USA
2
1
1
1
0
1
0
1
Korovessis et al.
2006
Greece
3
0
0
0
0
3
0
3
Nakase et al.26
2006
Japan
2
2
2
2
0
0
0
0
Dimar et al.
2004
USA
5
0
0
0
0
5
0
5
Shad et al.16
2003
UK
5
2
2
2
0
3
1
2
2003
Czech Republic
3
0
0
0
0
3
3
0
Schimmer et al.
2002
Switzerland
14
2
2
2
0
12
3
9
Hadjipavlou et al.15
2000
USA
6
0
0
0
0
6
0
6
1999
USA
14
8
8
8
1
5
0
5
1987
USA
4
0
0
0
4
0
0
0
NA
NA
210
136 (64.8% of total patients)
116 (85.3% of anterior approach)
104 (76.5% of anterior approach)
7 (3.3% of total patients)
67 (31.9% of total patients)
10 (14.9% of combined approach)
57 (85.1% of combined approach)
Auguste et al.18 14
31
Suchomel et al.29 1
Rezai
13
Zigler et al.30 Total
ORIGINAL ARTICLE
NA, not applicable. *Unable to determine surgical approach.
CERVICAL SPINE OSTEOMYELITIS AND INSTRUMENTED FUSION
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Lu et al.
AMY J. WANG ET AL.
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Table 1. Distribution of Surgical Approaches and Instrumentation Type
ORIGINAL ARTICLE AMY J. WANG ET AL.
Also, we found isolated reports of Eikenella corrodens, Propionybacterium acnes, Proteus mirabilis, and Pasteurella species. The duration of intravenous antibiotic therapy was extracted from 18 of the 24 articles (Table 2). The duration of initial postoperative intravenous antibiotic administration ranged from 2 to 12 weeks for patients with nontubercular osteomyelitis, with most studies reporting treatment lengths of >4 weeks (10 of 18 articles). Patients were treated for 10e12 weeks in 1 study,10 6 weeks in 6 studies,13,15,24,26,27,32 and 4e6 weeks in 3 studies.17,20,22 Additional oral antibiotic therapy after intravenous administration was reported by 11 studies, and the patients received oral antibiotics for a range of 3e24 weeks. For patients with M. tuberculosis identified in their cultures, antibiotic therapy was, as expected, much longer, ranging from 36 weeks to lifelong therapy.20,22,24 Fusion Rates The follow-up duration ranged from 6 weeks to 11 years (11 of 24 studies), with a mean follow-up period of 31.0 months (n ¼ 99 patients; 11 of 24 studies). The fusion rates were explicitly reported by 14 studies (Table 3). Of the 14 studies, 13 reported a 100% fusion rate (n ¼ 117 patients), and 1 study reported pseudarthrosis in 92.9% (n ¼ 13 of 14 patients meeting the criteria).1 Two additional studies reported they were unable to assess the fusion rates because the follow-up imaging studies were performed using magnetic resonance imaging and plain radiographs subject to artifact from cage implants.24,32 One additional study reported radiographically confirmed fusion in 2 of 3 patients, because the third patient had only been followed up for 3 months at the reporting of the study.29 Pain and Neurological Outcomes Of the 67 patients who presented in pain (95.7% of 70 patients; 9 studies), 100% experienced pain improvement after surgery. Pain improvement was assessed using the visual analog scale (VAS) in 7 studies.10,14,18,20,25,28 The mean preoperative VAS score for patients with cervical spine osteomyelitis ranged from 6.25 to 9 across the 7 studies, and the mean postoperative VAS score ranged from 1.75 to 3.85 (n ¼ 53; 5 studies). The neurological outcomes were assessed using the Frankel grade classification in 5 studies,1,14,15,21,22 the American Spinal Injury Association Impairment Scale (ASIA) in 4 studies,10,11,20,28 and the Nurick grading system in 2 studies.18,25 For the patients assessed using the Frankel scale (n ¼ 23; 3 studies), 16 (70.0%) presented with either motor or sensory neurological deficits, with 2 (8.7%) graded as Frankel A. After treatment, 8 patients (34.7%) had persistent neurological deficits. For the patients assessed using the ASIA (n ¼ 47; 3 studies), 36 (76.6%) presented with either motor or sensory neurological deficits. Preoperatively, most of these patients had been graded as ASIA D (n ¼ 22; 46.8%) or ASIA C (n ¼ 12; 25.5%). No patient had been graded as ASIA A. After surgical treatment and the at last follow-up examination, 33 of the 47 ASIA-graded patients (70.2%) were graded as ASIA E. The remaining 14 patients with a persistent deficit were all graded as ASIA D (29.8%; Figure 2). Hardware Failure and Wound Complications Rates The incidence of hardware failure was 4.6% (n ¼ 10 of 217 patients; 19 of 24 studies). The incidence of wound complications
WORLD NEUROSURGERY -: e1-e11, - 2018
CERVICAL SPINE OSTEOMYELITIS AND INSTRUMENTED FUSION
was 4.0% (n ¼ 9 of 226 patients; 21 of 24 studies). Hardware failure was defined as reoperation for screw loosening or pull out or graft subsidence. Wound complications and infections were defined as reoperation for wound infection and/or removal of hardware because of continued infection (Tables 4 and 5). Mortality The postoperative mortality rate was 4.1% (n ¼ 8 of 196 patients; 21 of 24 studies).1,6,10-18,21-24,26-30,32 The cause of death was sepsis in 5 patients,11,12 pneumonia in 1 patient,17 complications of malignancy in 1 patient,12 and unspecified in 1 patient (whose history included cardiac insufficiency and chronic alcohol abuse).21 DISCUSSION Cervical spine osteomyelitis poses a challenging management problem for multidisciplinary clinicians in neurosurgery, orthopedic surgery, infectious disease, and internal medicine. We performed a systematic review to assess the pain and neurological outcomes and surgical complication rates for patients who had undergone instrumented fusion, in addition to surgical debridement or decompression. To the best of our knowledge, the present study is the first systematic review of cervical osteomyelitis in >1 decade, and many postoperative outcomes such as neurologic status and hardware revision had not been fully explored.8 Our results suggest low rates of hardware failure and low rates of wound complications in patients with spontaneous pyogenic cervical spondylodiscitis treated with spinal instrumentation. It is important to contextualize the present study within the previous studies investigating the efficacy of surgical management compared with medical management. Comparisons in the previous studies were sparse, however, because although nonoperative management can be attempted first, many surgical candidates constitute those for whom medical therapy has failed and/or who had additional concerning symptoms such as neurologic compression, deformity, or biomechanical instability. In 2015, Alton et al.33 demonstrated a 75% failure rate with medical treatment alone in patients with cervical spinal epidural abscess (18 of 24). They had defined failure as a decline in motor function during intravenous antibiotic therapy.33 Although that study had excluded patients with isolated discitis or osteomyelitis,33 epidural abscesses have been reported to complicate spondylodiscitis at a rate of 90% in the cervical spine (vs. 33.3% in the thoracic spine and 23.6% in the lumbar spine).15 The demographics of the patient population were largely consistent with those from previous reviews, with an average age of 57 years (vs. 57e60 years) and a 64% male predominance (compared with 66%e87%).8 In line with previous reviews,6,8 the major comorbidities identified were diabetes, intravenous drug use, alcohol abuse, and renal insufficiency. Although chronic immunosuppression and distant infections have been frequently cited as risk factors for cervical spine infection, these were infrequently described in the articles included in our study. It is important to consider these results in the context of potential geographic limitations resulting from the inclusion of only English-language articles. Although our review was able to include articles from a range of countries, including China, Korea, Japan,
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Patients Meeting Microbiology S. S. Streptococcus P. M. Criteria (n) Identified (n) aureus (n) epidermidis (n) spp. (n) E. coli (n) aeruginosa (n) tuberculosis (n)
Investigator
Year
Country
Li et al.10
2017
China
14
12
7
1
2
1
0
0
0
10e12
Yesy
D’Souza et al.27
2016
USA
4
4
0
0
0
0
1
0
1 Eikenella; 2 polymicrobial
6
NR
Zhang et al.28
2016
China
24
17
11
4
0
2
0
0
0
3e6
4e10
Bydon et al.19
2014
USA
29
NSz
NA
NA
NA
NA
NA
0
0
NR
NR
4
0
5.5
8.3
0
3
3e9
1 P. acnes
4.2
6
20
Other (n)
IV Oral Antibiotics* Antibiotics* (weeks) (weeks)
Hahn et al.
2014 South Korea
5
4
3
0
0
0
1
Özkan et al.21
2014
Germany
18
NSz
NA
NA
NA
NA
NA
2013
Taiwan
5
5
3
Shousha et al.
2012
Germany
29
NSz
NA
NA
NA
NA
NA
NA
NA
Yesy
8e12
Rayes et al.12
2010
USA
26
22
17
0
1
0
3
0
1 Klebsiella spp.
Yesx
Yesx
Walter et al.
2010
Germany
4
4
4
0
0
0
0
0
0
3
9
Lu et al.24
2009
USA
5
5
5
0
0
0
0
1
0
6
NR
2009
Germany
5
5
5
0
0
0
0
0
0
6
NR
Tsai et al.22 11
23
25
Acosta et al.
2008
USA
4
NR
NA
NA
NA
NA
NA
NA
NA
NR
NR
Suess et al.17
2007
Germany
3
2
1
0
0
0
0
0
1 Proteus mirabilis
4e6
6
2006
USA
2
NR
NA
NA
NA
NA
NA
NA
NA
NR
NR
2006
Greece
3
3
2
1
0
0
0
0
0
4e6
Yesy
Auguste et al.18 14
Korovessis et al. 26
2006
Japan
2
1
1
0
0
0
0
0
0
6e8
8
Dimar et al.31
2004
USA
5
3
3
0
0
0
0
0
0
6
NR
Shad et al.16
2003
UK
5
5
4
1
0
0
0
0
0
12
Yesy
Suchomel et al.29
2003
Czech Republic
3
3
3
0
0
0
0
0
0
3
3
Schimmer et al.1
2002 Switzerland
13
11
7
0
2
2
0
1
1 Klebsiella spp.
NR
NR
Nakase et al.
Hadjipavlou et al.15 2000
USA
6
NS*
NA
NA
NA
NA
NA
NA
NA
6
6
Rezai13
1999
USA
14
NS*
NA
NA
NA
NA
NA
NA
NA
6
Yesy
Zigler et al.31
1987
USA
4
4
3
0
0
0
0
0
1 Pasteurella spp.
2e9
6e72
ORIGINAL ARTICLE
S. aureus, Staphylococcus aureus; S. epidermidis, Staphylococcus epidermidis; E. coli, Escherichia coli; P. aeruginosa, Pseudomonas aeruginosa; M. tuberculosis, Mycobacterium tuberculosis; IV, intravenous; NR, not reported; NS, not specific; NA, not applicable; P. acne, Propionybacterium acnes. *Antibiotic durations reported for nonetuberculosis osteomyelitis. ySpecific duration of treatment not provided. zNot specific for patients meeting review criteria. xAdministered for 6 weeks but route not specified.
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Mondorf et al.
32
1
AMY J. WANG ET AL.
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Table 2. Patient Microbiology Data and Antibiotic Treatment Duration
ORIGINAL ARTICLE AMY J. WANG ET AL.
CERVICAL SPINE OSTEOMYELITIS AND INSTRUMENTED FUSION
Table 3. Patient Fusion Outcomes and Rates of Hardware Failure and Wound Complications Hardware Failure Investigator
Wound Complications
Year
Country
Fusion Rate (%)
Patients (n)
Total Meeting Criteria (n)
Patients (n)
Total Meeting Criteria (n)
2017
China
100 (14/14)
0
14
0
14
D’Souza et al.
2016
USA
NR
NR
NA
1
4
28
Zhang et al.
2016
China
100 (24/24)
0
24
0
24
Bydon et al.19
2014
USA
NS*
1
29
3
29
Hahn et al.
2014
South Korea
NR
0
9
0
9
Özkan et al.21
2014
Germany
NR
1
18
1
18
2013
Taiwan
100 (5/5)
0
6
1
6
2012
Germany
100 (29/29)
2
29
0
29
2010
USA
NR
0
26
0
26
Walter et al.
2010
Germany
100 (4/4)
0
4
0
4
Lu et al.24
2009
USA
NDy
0
6
0
6
Mondorf et al.
2009
Germany
NDy
1
5
0
5
25
Acosta et al.
2008
USA
100 (4/4)
0
4
0
4
Suess et al.17
2007
Germany
NS*
0
3
0
3
10
Li et al.
27
20
Tsai et al.22 Shousha et al.
11
Rayes et al.12 23
32
18
Auguste et al.
2006
USA
100 (2/2)
0
2
0
2
Korovessis et al.14
2006
Greece
100 (3/3)
0
3
0
3
Nakase et al.26
2006
Japan
100 (2/2)
0
2
0
2
Dimar et al.
2004
USA
NR
NS*
NA
0
5
Shad et al.16
2003
UK
100 (5/5)
0
5
0
5
2003
Czech Republic
66.7 (2/3)z
NR
NA
NR
NA
31
Suchomel et al.29 1
Schimmer et al.
2002
Switzerland
92.9 (13/14)
1
14
2
14
Hadjipavlou et al.15
2000
USA
100 (6/6)
NR
NA
NR
NA
Rezai13
1999
USA
100 (14/14)
4
14
1
14
Zigler et al.31
1987
USA
100 (4/4)
NR
NA
NR
NA
NA
NA
NA
10 (4.6)
217
9 (4.0)
226
Total
NR, not reported; NA, not available; NS, not specific; ND, not done. *Not specific for patients meeting review criteria. yInvestigators were unable to assess for fusion radiographically. zTwo of 3 patients achieved fusion; the third had been followed up for 3 months at the report of the study and had not yet achieved fusion.
Germany, and Greece, these countries do not necessarily represent a diverse sampling of patients with spondylodiscitis and likely represent a publication bias favoring developed countries with more established academic infrastructures for publication. For example, the incidence of tuberculosis varies greatly worldwide, with nearly 50% of all reported cases from Southeast Asia.34 The few cases of instrumented treatment for tuberculosis osteomyelitis described in the present review likely could not capture the full range of potential surgical outcomes. Regarding the bacteriological diagnoses, the rate of culturepositive cases and the predominance of S. aureus were consistent with the vertebral osteomyelitis data elsewhere in the spine.
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Definitive organisms were cultured for 85.4% of patients with cervical spine osteomyelitis compared with 85%e88% of patients with vertebral osteomyelitis in various locations.7,35 Within the vertebral osteomyelitis data, the rate of S. aureus within culture-positive cases has been reported to be 42.7%e57.2%, with 43.8%e49.1% of cases reported to MRSA.35,36 For the cervical osteomyelitis patients, S. aureus was also the most commonly isolated organism. However, S. aureus represented a greater proportion of culture-positive cases of 71.8%, with similar rates of MRSA at 44.0%. The next most frequently isolated organisms were Streptococcus spp. and S. epidermidis. The most commonly isolated gram-negative bacteria were E. coli and P. aeruginosa.
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Figure 2. Preoperative versus postoperative neurological function measured using (Top) American
Our series also examined tubercular infections of the cervical spine. These were relatively uncommon, comprising <3% of our series, which might be expected in the modern era owing to both the declining rates of tubercular infection and the greater propensity of tuberculosis to affect the thoracic spine.37,38 Given their relative rarity in our series, it was difficult to draw too many definitive comparisons with our larger cohort, and dedicated examination of cervical tubercular osteomyelitis might be warranted. However, given M. tuberculosis’ well-documented propensity elsewhere in the spine for anterior column destruction and
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Spinal Injury Association (ASIA) and (Bottom) Frankel grading system.
antibiotic resistance requiring prolonged multidrug treatment regimens, infections from this organism likely represent a distinct pathologic process from other types of cervical bacterial osteomyelitis and warrant special attention to anterior load-sharing and adequate antibiotic compliance. Until recently, the recommended duration of treatment in the vertebral osteomyelitis data had been extrapolated from observational studies and ranged from 4 to 12 weeks.39-43 In the present study, patients with cervical osteomyelitis received intravenous antibiotic treatment for a range of 2 to 12 weeks, with a plurality of
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Table 4. Reported Hardware Failures Investigator
Year Hardware Failure (n)
Bydon et al.19
2014
1
Hardware failure, NOS
Özkan et al.
2014
1
PMMA implant dislocation
Shousha et al.11 2012
2
Screw dislocations
2009
1
PEEK cage explanted and bone graft inserted at different hospital
Schimmer et al. 2002
1
Hardware failure, NOS
Rezai13
4
1, Screw dislocation/pull out; 2, bone graft extrusion requiring reoperation; 1, graft collapse and screw dislocation
21
32
Mondorf et al.
1
1999
Description
NOS, not otherwise specified; PMMA, poly(methyl methacrylate); PEEK, polyetheretherketone.
studies conforming to the 4e6-week window. In 2015, a randomized controlled trial studying the treatment duration for patients with pyogenic vertebral osteomyelitis demonstrated that 6 weeks of antibiotic treatment is not inferior to 12 weeks, with respect to the cure rate, with 90.9% of the 6-week group and 90. 9% of the 12-week group meeting the criteria for clinical cure at 1 year.44 Although most studies included in the present review continued to treat their patients with oral antibiotics after intravenous administration, no consensus has been reached on the use of oral antibiotics. Individual treatment regimens should always consider a patient’s individual circumstances and the advice from a local infectious disease consultation. Most patients with cervical spine osteomyelitis reported pain on presentation, and the vast majority experienced improvement after surgical debridement and instrumentation. The studies that assessed pain using the VAS demonstrated a decrease in the average VAS score postoperatively, followed by a continued decrease at the last follow-up visit. This finding reaffirms previous findings that surgery can lead to significant improvements in pain. In 1 study comparing surgical and medical management in patients with vertebral osteomyelitis across all levels, 64.3% of the nonsurgically treated group continued to report disabling back pain compared with 26.3% of the surgically treated group.15 Pain persistence in the nonsurgically treated group was often due to kyphosis and pseudarthrosis.15 Although most patients presented with a neurologic deficit (70% using the Frankel grading system and 77% using the ASIA system), few patients presented with a complete deficit. After surgery, approximately one half of the patients in our review were
neurologically intact. Neurological function continued to improve throughout the follow-up period, as evidenced by the 70% patients without neurologic deficit (using the ASIA) at the last follow-up examination. These results confirm that in well-selected patient populations, significant rates of neurologic improvement can be expected postoperatively. This has been mirrored in the thoracolumbar data, with 84%e90% of patients with preoperative deficits reporting improved neurologic status postoperatively.45-47 However, despite the high rates of improvement, these data also highlight the significant morbidity of cervical involvement, with the remaining 30% of patients having persistent neurologic deficits. The present study found a 4.6% reoperation rate for hardware failure and a 4.0% reoperation rate for wound complications. Although instrumentation was performed in an infected space, these rates compare favorably with the data reported from elective degenerative cervical spine cases. Recent large database studies have demonstrated a lower rate of infection for anterior cervical fusion at 0.4%e0.65%48,49 compared with a 3.7% rate associated with posterior cervical fusion.50 In addition, circumferential cervical fusion for noninfectious indications has been associated with a reoperation rate for wound infection of 4.8%e6.7% and for hardware failure of 4.8%.51,52 Our results suggest that despite a priori fears of placing a foreign body in an infected space, the rates of hardware failure and wound infection requiring reoperation might be comparable to other elective cervical spine procedures. Our study had several limitations. First, the primary studies were largely retrospective, and, perhaps by necessity, the patient
Table 5. Reported Wound Complications Investigator
Year
Wound Complication (n)
Description
D’Souza et al.
2016
1
Further decompression and instrumentation for persistent infection
19
Bydon et al.
2014
3
Unspecified reoperation for wound complication
Özkan et al.21
2014
1
Further decompression alone after new abscess development
2013
1
Further decompression and instrumentation for persistent infection
Schimmer et al.
2002
2
1, Hardware removal for persistent infection; 1 tracheostomy and gastrostomy because of deep anterior wound infection
Rezai13
1999
1
Hardware removal for persistent infection
27
22
Tsai et al.
1
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populations were often small and heterogeneous with respect to comorbidities and intraoperative techniques. As such, the present study lacked the statistical power to delineate the optimal surgical management for these patients regarding the approach, surgical technique, graft type, and length of postoperative antibiotics. Another issue was that many studies had broader inclusion criteria than ours (e.g., patients with vertebral osteomyelitis at any location), and we incurred loss of information by including only those subsets of patients relevant to our study. It is possible that excluding studies in this manner incurred a bias. In addition, systematic reviews, by necessity, are influenced by publication bias. This was shown in that the 239 patients isolated in our study represented but a small fraction of the overall incidence of cervical osteomyelitis during the >30-year period reviewed in our series. We attempted to limit the effect of publication bias by excluding single-patient case studies. Nevertheless, a distinct possibility remains that the reported results have underestimated the true
REFERENCES 1. Schimmer RC, Jeanneret C, Nunley PD, Jeanneret B. Osteomyelitis of the cervical spine: a potentially dramatic disease. J Spinal Disord Tech. 2002;15:110-117. 2. Urrutia J, Zamora T, Campos M. Cervical pyogenic spinal infections: are they more severe diseases than infections in other vertebral locations? Eur Spine J. 2013;22:2815-2820. 3. Kremers H, Nwojo M, Ransom J, Wood-Wentz C, Melton L, Huddleston P. Trends in the epidemiology of osteomyelitis: a population-based study, 1969 to 2009. J Bone Joint Surg Am. 2015;97:837-845. 4. Kehrer M, Pedersen C, Jensen T, Lassen A. Increasing incidence of pyogenic spondylodiscitis: a 14-year population-based study. J Infect. 2014; 68:313-320.
incidence of wound complications and hardware malfunctions in clinical practice. Thus, although the present systematic review has begun to complete the knowledge gap, future prospective series are still needed. CONCLUSION Our review has demonstrated high rates of fusion and relatively low rates of hardware failures and wound revisions and infections in patients presenting with spontaneous cervical spondylodiscitis and osteomyelitis. Most patients experienced pain relief and improved neurologic function postoperatively, although a significant minority of patients continued to experience long-term neurologic deficits. These results suggest that surgical debridement with placement of instrumentation can be a safe and effective treatment for cervical spine infection.
11. Shousha M, Boehm H. Surgical treatment of cervical spondylodiscitis. Spine (Phila Pa 1976). 2012;37: E30-E36.
spondylodiscitis—a clinical analysis of surgically treated patients and review of the literature. Clin Neurol Neurosurg. 2014;117:86-92.
12. Rayes M, Colen CB, Bahgat DA, Higashida T, Guthikonda M, Rengachary S, et al. Safety of instrumentation in patients with spinal infection. J Neurosurg Spine. 2010;12:647-659.
22. Tsai CE, Lee FT, Chang MC, Yu WK, Wang ST, Liu CL. Primary cervical osteomyelitis. J Chinese Med Assoc. 2013;76:640-647.
13. Rezai AR. Contemporary management of spinal osteomyelitis. Neurosurgery. 1999;44:1018-1025. 14. Korovessis P, Petsinis G, Koureas G, Iliopoulos P, Zacharatos S. One-stage combined surgery with mesh cages for treatment of septic spondylitis. Clin Orthop Relat Res. 2006;443:51-59. 15. Hadjipavlou AG, Mader JT, Necessary JT, Muffoletto AJ. Hematogenous pyogenic spinal infections and their surgical management. Spine (Phila Pa 1976). 2000;25:1668-1679.
5. Sur A, Tsang K, Brown M, Tzerakis N. Management of adult spontaneous spondylodiscitis and its rising incidence. Ann R Coll Surg Engl. 2015;97: 451-455.
16. Shad A, Shariff S, Fairbank J, Byren I, Teddy PJ, Cadoux-Hudson TA. Internal fixation for osteomyelitis of cervical spine: the issue of persistence of culture positive infection around the implants. Acta Neurochir (Wien). 2003;145:957-960.
6. Acosta FL, Chin CT, Quiñones-Hinojosa A, Ames CP, Weinstein PR, Chou D. Diagnosis and management of adult pyogenic osteomyelitis of the cervical spine. Neurosurg Focus. 2004;17:1-9.
17. Suess O, Weise L, Brock M, Kombos T. Debridement and spinal instrumentation as a single-stage procedure in bacterial spondylitis/spondylodiscitis. Zentralbl Neurochir. 2007;68:123-132.
7. Mylona E, Samarkos M, Kakalou E, Fanourgiakis P, Skoutelis A. Pyogenic vertebral osteomyelitis: a systematic review of clinical characteristics. Semin Arthritis Rheum. 2009;39: 10-17. 8. Barnes B, Alexander JT, Branch CL. Cervical osteomyelitis: a brief review. Neurosurg Focus. 2004; 17:E11.
18. Auguste KI, Chin C, Acosta FL, Ames CP. Expandable cylindrical cages in the cervical spine: a review of 22 cases. J Neurosurg Spine. 2006;4: 285-291. 19. Bydon M, De La Garza-Ramos R, Macki M, Naumann M, Sciubba DM, Wolinsky JP, et al. Spinal instrumentation in patients with primary spinal infections does not lead to greater recurrent infection rates: an analysis of 118 cases. World Neurosurg. 2014;82:E807-E814.
9. Stewart L, Clarke M, Rovers M, Riley RD, Simmonds M, Stewart G, et al. Preferred reporting items for systematic review and meta-analyses of individual participant data: the PRISMA-IPD statement. JAMA. 2015;313:1657-1665.
20. Hahn BS, Kim K-H, Kuh S-U, Park JY, Chin D-K, Kim K-S, et al. Surgical treatment in patients with cervical osteomyelitis: single institute’s experiences. Korean J Spine. 2014;11:162-168.
10. Li H, Chen Z, Yong Z, Li X, Huang Y, Wu D. Medicine (Baltimore). 2017;96:e7301.
21. Özkan N, Wrede K, Ardeshiri A, Hagel V, Dammann P, Ringelstein A, et al. Cervical
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23. Walter J, Kuhn SA, Reichart R, Kalff R, Ewald C. PEEK cages as a potential alternative in the treatment of cervical spondylodiscitis: a preliminary report on a patient series. Eur Spine J. 2010;19:1004-1009. 24. Lu DC, Wang V, Chou D. The use of allograft or autograft and expandable titanium cages for the treatment of vertebral osteomyelitis. Neurosurgery. 2009;64:122-129. 25. Acosta FL, Aryan HE, Chou D, Ames CP. Longterm biomechanical stability and clinical improvement after extended multilevel corpectomy and circumferential reconstruction of the cervical spine using titanium mesh cages. J Spinal Disord Tech. 2008;21:165-174. 26. Nakase H, Tamaki R, Matsuda R, Tei R, Park Y-S, Sakaki T. Delayed reconstruction by titanium meshebone graft composite in pyogenic spinal infection. Infection. 2006;19:48-54. 27. D’Souza JN, Luginbuhl AJ, Goldman RA, Heller JE, Curry JM, Cognetti DM. Cervical spine spondylodiscitis after esophageal dilation in patients with a history of laryngectomy or pharyngectomy and pharyngeal irradiation. JAMA Otolaryngol Neck Surg. 2016;142:467-471. 28. Zhang Z, Li T, Hao D. Single-stage treatment of osteomyelitis of the cervical spine using anterior instrumentation and titanium mesh cages. Spine (Phila Pa 1976). 2016;41:E949-E954. 29. Suchomel P, Buchvald P, Barsa P, Lukas R, Soukup T. Pyogenic osteomyelitis of the odontoid process: single stage decompression and fusion. Spine (Phila Pa 1976). 2003;28:E239-E244. 30. Zigler JE, Bohlman HH, Robinson RA, Riley LH, Dodge LD. Pyogenic osteomyelitis of the occiput, the atlas, and the axis: a report of five cases. J Bone Joint Surg Am. 1987;69:1069-1073.
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31. Dimar JR, Carreon LY, Glassman SD, Campbell MJ, Hartman MJ, Johnson JR. Treatment of pyogenic vertebral osteomyelitis with anterior debridement and fusion followed by delayed posterior spinal fusion. Spine (Phila Pa 1976). 2004;29: 326-332 [discussion: 332]. 32. Mondorf Y, Gaab MR, Oertel JMK. PEEK cage cervical ventral fusion in spondylodiscitis. Acta Neurochir (Wien). 2009;151:1537-1541. 33. Alton TB, Patel AR, Bransford RJ, Bellabarba C, Lee MJ, Chapman JR. Is there a difference in neurologic outcome in medical versus early operative management of cervical epidural abscesses? Spine J. 2015;15:10-17. 34. Raviglione M, Snider D, Kochi A. Global epidemiology of tuberculosis morbidity and mortality of a worldwide epidemic. JAMA. 1995;273:220-226. 35. Weissman S, Parker R, Siddiqui W, Dykema S, Horvath J. Vertebral osteomyelitis: retrospective review of 11 years of experience. Scand J Infect Dis. 2014;46:193-199. 36. Kim J, Kim YS, Peck KR, Kim ES, Cho SY, Ha YE, et al. Outcome of culture-negative pyogenic vertebral osteomyelitis: comparison with microbiologically confirmed pyogenic vertebral osteomyelitis. Semin Arthritis Rheum. 2014;44:246-252. 37. Turgut M. Spinal tuberculosis (Pott’s disease): its clinical presentation, surgical management, and outcome: a survey study on 694 patients. Neurosurg Rev. 2001;24:8-13. 38. Scott C, Kirking HL, Jeffries C, Price SF, Pratt R. Tuberculosis trends—United States, 2014. Morb Mortal Wkly Rep. 2015;64:265-269. 39. Livorsi DJ, Daver NG, Atmar RL, Shelburne SA, White AC, Musher DM. Outcomes of treatment for hematogenous Staphylococcus aureus vertebral osteomyelitis in the MRSA era. J Infect. 2008;57: 128-131.
CERVICAL SPINE OSTEOMYELITIS AND INSTRUMENTED FUSION
40. Sapico F. Microbiology and antimicrobial therapy of spinal infections. Orthop Clin North Am. 1996;27: 9-13. 41. Osenbach R, Hitchon P, Menezes A. Diagnosis and management of pyogenic vertebral osteomyelitis in adults. Surg Neurol. 1990;33:266-275. 42. Roblot F, Besnier J, Juhel L, Vidal C, Ragot S, Bastides F, et al. Optimal duration of antibiotic therapy in vertebral osteomyelitis. Semin Arthritis Rheum. 2007;36:269-277. 43. McHenry M, Easley K, Locker G. Vertebral osteomyelitis: long-term outcome for 253 patients from 7 Cleveland area hospitals. Clin Infect Dis. 2002;34:1342-1350. 44. Bernard L, Dinh A, Ghout I, Simo D, Zeiler V, Issartei B, et al. Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial. Lancet. 2015;385: 875-882. 45. Dai LY, Chen WH, Jiang LS. Anterior instrumentation for the treatment of pyogenic vertebral osteomyelitis of thoracic and lumbar spine. Eur Spine J. 2008;17:1027-1034. 46. Rath SA, Neff U, Schneider O, Richter HP. Neurosurgical management of thoracic and lumbar vertebral osteomyelitis and discitis in adults: a review of 43 consecutive surgically treated patients. Neurosurgery. 1996;38:926-933. 47. Ruf M, Stoltze D, Merk HR, Ames M, Harms J. Treatment of vertebral osteomyelitis by radical debridement and stabilization using titanium mesh cages. Spine (Phila Pa 1976). 2007;32: E275-E280.
2164 patients from the American College of Surgeons National Surgical Quality Improvement Project Database (ACS NSQIP). Clin Spine Surg. 2016;29:E34-E42. 49. Veeravagu A, Cole T, Jiang B, Ratliff JK. Revision rates and complication incidence in single-and multilevel anterior cervical discectomy and fusion procedures: an administrative database study. Spine J. 2014;14:1125-1131. 50. Sebastian A, Huddleston PI, Kakar S, Habermann E, Wagie A, Nassr A. Risk factors for surgical site infection after posterior cervical spine surgery: an analysis of 5,441 patients from the ACS NSQIP 2005e2012. Spine J. 2016;16:504-509. 51. Mummaneni PV, Dhall SS, Rodts GE, Haid RW. Circumferential fusion for cervical kyphotic deformity. J Neurosurg Spine. 2008;9:515-521. 52. Gok B, Sciubba DM, McLoughlin GS, McGirt M, Ayhan S, Wolinsky JP, et al. Surgical treatment of cervical spondylotic myelopathy with anterior compression: a review of 67 cases. J Neurosurg Spine. 2008;9:152-157.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 15 June 2018; accepted 16 August 2018 Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.08.129 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com
48. Gruskay JA, Fu M, Basques BA, Bohl DD, Buerba RA, Webb ML, et al. Factors affecting length of stay and complications after elective anterior cervical discectomy and fusion: a study of
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Cervical Spine Osteomyelitis: A Systematic Review of Instrumented Fusion in the Modern Era Amy J. Wang1, Kevin T. Huang1, Timothy R. Smith1,2, Yi Lu1, John H. Chi1, Michael W. Groff1,2, Hasan A. Zaidi1,2
OBJECTIVE: For cases of cervical osteomyelitis that require surgery, concern has continued regarding instrumentation owing to the potential for bacterial seeding of the hardware. We performed a systematic review of the current data.
-
METHODS: A search was performed using Medline, Embase, and Ovid for articles using the keywords “cervical osteomyelitis/spondylodiscitis” and “fusion” or “instrumentation” reported from 1980 to 2017. Prospective or retrospective studies describing ‡2 patients with cervical osteomyelitis were included in the analysis; non-English reports were excluded. Individual patients were excluded from the final analysis if they had previously undergone spinal instrumentation.
complications were comparable to those of elective cervical spine procedures. These results suggest that surgical intervention with instrumentation is a safe treatment option for patients with cervical spine osteomyelitis.
-
RESULTS: A total of 239 patients from 24 studies met our criteria. Surgical approaches were classified as anterioronly, combined anteroposterior, and posterior-only for 64.8%, 31.9%, and 3.3% of the patients respectively. Of the patients treated using an anterior-only approach, 76.5% had received anterior plating and 85.3%, a cage or spacer implants. Of the patients who had undergone combined approaches, 85.1% underwent circumferential fixation and 14.9%, anterior debridement with posterior instrumentation. The follow-up period ranged from 6 weeks to 11 years (mean, 31.0 months). All the studies reporting the fusion rates, except for 1, reported a 100% fusion rate. The reported rates of pain improvement and neurologic recovery were favorable. The incidence of hardware failure and wound complications was 4.6% and 4.0%, respectively.
-
CONCLUSIONS: Despite placing instrumentation during active infection, the rates of hardware failure and wound
-
Key words - Cervical osteomyelitis - Cervical spondylodiscitis - Instrumented fusion Abbreviations and Acronyms ASIA: American Spinal Injury Association MRSA: Methicillin-resistant Staphylococcus aureus VAS: Visual analog scale
INTRODUCTION
C
ervical spine infections necessitate urgent treatment owing to the potential for severe neurologic complications and compromise of the integrity of the vertebral column. Compared with the thoracic and lumbar regions, the cervical spine permits a greater range of motion and the cervical spinal cord occupies a larger portion of the canal. These characteristics allow spondylodiscitis of the cervical spine to progress more rapidly and result in catastrophic neurological deficits.1,2 One retrospective study observed significantly greater rates of neurological involvement (68.4% vs. 41%) and mortality (21.2% vs. 3.6%) in patients with cervical spine pyogenic infections compared with patients with thoracolumbar infections.2 The incidence of vertebral osteomyelitis throughout the spine has been steadily increasing. In the United States, 1 population study estimated an incidence of 4.7 cases per 100,000 persons annually from 2000 to 2009, an increase from 0.5 cases per 100,000 persons annually from 1969 to 1979.3 Recent studies from Denmark and England have reported similar numbers and trends.4,5 Of these vertebral osteomyelitis cases, cervical spine osteomyelitis represents an estimated 3%e11%.6,7 Despite the relative rarity of cervical spine infections, the potentially devastating consequences, together with the increasing incidence of the disease, demonstrate a pressing need for determining optimal management.
From the 1Department of Neurosurgery and 2Computational Neuroscience Outcomes Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA To whom correspondence should be addressed: Hasan A. Zaidi, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.08.129 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Published by Elsevier Inc.
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Although the preferred treatment of cervical osteomyelitis is medical, surgical treatment is indicated for cases in which signs of biomechanical instability or neurologic compromise are present, or when the diagnosis needs to be established. Surgical treatment of cervical osteomyelitis involves debridement with or without instrumented fusion, using an anterior, a posterior, or a combined approach. Instrumentation is thought to improve the fusion rates and is routinely used to aid in fusion in noninfectious cases. However, because of concern for bacterial seeding on the hardware after placement of foreign materials in an active infection, the safety and efficacy of instrumentation for cervical spine infections continues to be debated. The existing data on the surgical management of cervical spine infections consist mostly of small, institutional series reporting heterogeneous patient groups. Moreover, to the best of our knowledge, more than 1 decade has elapsed since the most recent reviews of the subject, which had their own limitations in scope.6,8 Thus, we performed a systematic review of the current data focusing on patients with pyogenic cervical osteomyelitis or spondylodiscitis who underwent instrumented fusion. METHODS The systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.9 A search was conducted using Medline, Embase, and Ovid databases for articles with the keywords (“cervical osteomyelitis” OR “cervical spondylodiscitis”) AND (“fusion” OR “instrumentation”), reported from January 1980 to October 2017. Original, peer-reviewed, prospective, or retrospective studies with 2 cases of cervical spine infection were included in an initial screen. Case reports and other single-patient publications were excluded to reduce the effect of publication bias of unusual or nonrepresentative cases. Other exclusion criteria consisted of nonEnglish manuscripts and nonoperative series. If >1 publication had reported on the same patient cohort, the publication reporting the most comprehensive and relevant clinical data was included in the final analysis. The resulting articles were reviewed by 2 independent investigators (A.J.W. and K.T.H). Within each article, the patients were included in the final analysis only if they had undergone spinal instrumentation for cervical osteomyelitis or spondylodiscitis. The patients were excluded if their infection had developed from a complication of an index cervical spinal surgery or if they had been treated with noninstrumented fusion or debridement and/or decompression alone. Patients with fungal infections, because they represented a cohort with separate risk factors, comorbidities, pathophysiology, and treatment paradigms, were not included in the present study. Publications that had aggregated clinical data for a heterogeneous patient cohort such that it prevented isolation of data regarding the patients of interest, the article was removed from the analysis. If the 2 investigators disagreed on whether an article met the inclusion criteria, a third investigator (H.A.Z.) joined the discussion to reach a group consensus. We then extracted the following data from each article: study design, study country of origin, total number of patients meeting the criteria, risk factors and comorbidities, surgical approaches,
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instrumentation types, microbiology, length of antibiotic treatment, follow-up duration, pain and neurologic outcomes and the assessment tools used, fusion rates, incidence of hardware failure, and incidence of wound complication. Hardware failure was defined as screw loosening, screw pull-out, or graft subsidence. Wound complications were defined as reoperation for wound infection and/or removal of hardware because of persistent infection. A total of 309 articles were identified through the database searches. After filtering for English-language manuscripts, human subjects, and publication dates from January 1980 to October 2017, 183 unique articles remained available for title and abstract screening. Another 139 records were excluded for the following reasons: not relevant to cervical spine infection and instrumentation (n ¼ 69), individual case reports (n ¼ 51), series containing only 1 patient meeting the criteria (n ¼ 13), and review articles (n ¼ 6). The 2 investigators reviewed 44 full-text articles, of which 16 were eliminated because they had aggregated the clinical data for patients who did not meet our criteria. Another 3 were eliminated because they had included a cohort of patients who had also been included in another article. A total of 24 peer-reviewed journal articles were included in the final analysis: 18 retrospective series,1,10-26 5 case series,27-31 and 1 prospective cohort study32 (Figure 1). RESULTS Baseline Characteristics A total of 239 patients from 24 articles were included in the present study. The countries of origin were the United States,6,12,13,15,18,19,24,27,30,31 Germany,11,17,21,23,32 China,10,28 Korea,20 Taiwan,22 Japan,26 Greece,14 the United Kingdom,16 the Czech Republic,29 and Switzerland.1 All 239 patients had undergone instrumented fusion as part of their surgery. The male/female ratio was 1.8:1 (92 males [64.3%]; 51 females [35.7%]; 20 of 24 studies). The mean age across the included studies ranged from 49 to 84 years, and the mean age of the individual patients was 56.7 years (18 of 24 studies). Comorbidity data were only available for 14 of the 24 studies. The most common comorbidities were diabetes mellitus (n ¼ 26), intravenous drug use (n ¼ 23), and alcohol abuse (n ¼ 16). Other reported comorbidities included renal disease (n ¼ 8), heart disease (n ¼ 7), malignancy (n ¼ 5), remote infection (n ¼ 7, including endocarditis, n ¼ 1), hypertension (n ¼ 5), previous neck radiation (n ¼ 4), iatrogenic immunosuppression (n ¼ 1), and human immunodeficiency virus infection (n ¼ 1). Surgical Approach Regarding the surgical management, 136 patients (64.8%) underwent treatment by an anterior approach alone, 7 (3.3%) by a posterior approach alone, and 67 (31.9%) by a combined approach (all percentages computed from 210 patients from 23 of the 24 studies). For the remaining 29 patients, the surgical approach for placement of instrumentation was not specified.19 Of the 136 patients treated by an anterior-only approach, 104 (76.5%) were documented as having received anterior plating and 116 (85.3%) had received cage or spacer implants. Of the 67 patients who had undergone combined anterior and posterior approaches, 57 (85.1%) had undergone circumferential fixation, and 10 (14.9%) had undergone anterior debridement but with instrumentation
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CERVICAL SPINE OSTEOMYELITIS AND INSTRUMENTED FUSION
Figure 1. Flow diagram depicting study selection. C-spine, cervical spine.
from the posterior approach alone (including 6 who had undergone a transoral approach; (Table 1). Only 8 of 24 articles had reported definitively on which patients had undergone corpectomies.11,15,17,18,21,22,24,26 Of these studies, the rate of receiving any corpectomy (single vs. multilevel, not always specified) ranged from 13% to 100%, with several smaller series reporting that 100% of their patients had undergone corpectomies.15,17,18,24,26 However, most of these studies had not quantified the degree of bony debridement. Additionally, we did find evidence that the surgical approach differed by geographic region. When divided by continent, 52 patients (94.5%) in the Asian studies had undergone surgery with an anterior approach alone compared with 35 (49.3%) in the American cohort and 49 (58.3%) in the European cohort, with the vast majority of the rest receiving combined anteroposterior surgical approaches (n ¼ 30 [42.3%] in the U.S. group, n ¼ 35 [41.7%] in the European group, and n ¼ 2 [3.6%] in the Asian group). This difference was statistically significant when comparing the
WORLD NEUROSURGERY -: e1-e11, - 2018
surgical approach between patients from Asian and non-Asian countries of origin (P < 0.0001, c2 test). Microbiology Identified and Antibiotic Therapy We were able to extract microbiological data for our patients of interest from 17 of the 24 articles (Table 2). Of the 17 studies that reported culture data, 117 of 137 patients (85.4%) had organisms identified. Of these 117 patients, 115 (98.3%) had a single definitive organism identified. Also, for these 117 patients, Staphylococcus aureus was the most common causative agent, isolated in 79 of the patients (67.5%). Other etiologies included Staphylococcus epidermidis (n ¼ 7; 6.0%), Mycobacterium tuberculosis (n ¼ 7; 6.0%), Pseudomonas aeruginosa (n ¼ 5; 4.3%), Escherichia coli (n ¼ 5; 4.3%), Klebsiella species (n ¼ 2; 1.7%), polymicrobial (n ¼ 2; 1.7%), and various Streptococcus species (n ¼ 4; 3.4%). Within the S. aureus group, 44.0% of the cases with antibioticsensitivity data available were attributed to methicillin-resistant S. aureus (MRSA; n ¼ 11 of 25 patients; 3 studies reporting).
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Year
Country
Patients Meeting Criteria (n)
2017
China
14
14
14
14
0
0
0
0
D’Souza et al.
2016
USA
4
1
1
0
0
3
0
3
28
Zhang et al.
2016
China
24
24
24
24
0
0
0
0
Bydon et al.19
2014
USA
29*
0
0
0
0
0
0
0
Hahn et al.
2014
South Korea
9
6
6
0
1
2
0
2
Özkan et al.21
2014
Germany
18
16
16
13
0
2
1
1
2013
Taiwan
6
6
6
6
0
0
0
0
Shousha et al.
2012
Germany
29
17
17
5
0
12
2
10
Rayes et al.12
2010
USA
26
24
4
24
1
1
0
1
2010
Germany
4
4
4
0
0
0
0
0
Investigator Li et al.10 27
20
Tsai et al.22 11
23
Walter et al. 24
Anterior Approach Alone (n)
Cage or Spacer Implants (n)
Anterior Plating (n)
Posterior Approach Alone (n)
Combined Approach (n)
Anterior Debridement and Posterior Fixation (n)
Circumferential Fixation (n)
2009
USA
6
1
1
0
0
5
0
5
Mondorf et al.32
2009
Germany
5
5
5
0
0
0
0
0
Acosta et al.25
2008
USA
4
0
0
0
0
4
0
4
Suess et al.17
2007
Germany
3
3
3
3
0
0
0
0
2006
USA
2
1
1
1
0
1
0
1
Korovessis et al.
2006
Greece
3
0
0
0
0
3
0
3
Nakase et al.26
2006
Japan
2
2
2
2
0
0
0
0
Dimar et al.
2004
USA
5
0
0
0
0
5
0
5
Shad et al.16
2003
UK
5
2
2
2
0
3
1
2
2003
Czech Republic
3
0
0
0
0
3
3
0
Schimmer et al.
2002
Switzerland
14
2
2
2
0
12
3
9
Hadjipavlou et al.15
2000
USA
6
0
0
0
0
6
0
6
1999
USA
14
8
8
8
1
5
0
5
1987
USA
4
0
0
0
4
0
0
0
NA
NA
210
136 (64.8% of total patients)
116 (85.3% of anterior approach)
104 (76.5% of anterior approach)
7 (3.3% of total patients)
67 (31.9% of total patients)
10 (14.9% of combined approach)
57 (85.1% of combined approach)
Auguste et al.18 14
31
Suchomel et al.29 1
Rezai
13
Zigler et al.30 Total
ORIGINAL ARTICLE
NA, not applicable. *Unable to determine surgical approach.
CERVICAL SPINE OSTEOMYELITIS AND INSTRUMENTED FUSION
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Table 1. Distribution of Surgical Approaches and Instrumentation Type
ORIGINAL ARTICLE AMY J. WANG ET AL.
Also, we found isolated reports of Eikenella corrodens, Propionybacterium acnes, Proteus mirabilis, and Pasteurella species. The duration of intravenous antibiotic therapy was extracted from 18 of the 24 articles (Table 2). The duration of initial postoperative intravenous antibiotic administration ranged from 2 to 12 weeks for patients with nontubercular osteomyelitis, with most studies reporting treatment lengths of >4 weeks (10 of 18 articles). Patients were treated for 10e12 weeks in 1 study,10 6 weeks in 6 studies,13,15,24,26,27,32 and 4e6 weeks in 3 studies.17,20,22 Additional oral antibiotic therapy after intravenous administration was reported by 11 studies, and the patients received oral antibiotics for a range of 3e24 weeks. For patients with M. tuberculosis identified in their cultures, antibiotic therapy was, as expected, much longer, ranging from 36 weeks to lifelong therapy.20,22,24 Fusion Rates The follow-up duration ranged from 6 weeks to 11 years (11 of 24 studies), with a mean follow-up period of 31.0 months (n ¼ 99 patients; 11 of 24 studies). The fusion rates were explicitly reported by 14 studies (Table 3). Of the 14 studies, 13 reported a 100% fusion rate (n ¼ 117 patients), and 1 study reported pseudarthrosis in 92.9% (n ¼ 13 of 14 patients meeting the criteria).1 Two additional studies reported they were unable to assess the fusion rates because the follow-up imaging studies were performed using magnetic resonance imaging and plain radiographs subject to artifact from cage implants.24,32 One additional study reported radiographically confirmed fusion in 2 of 3 patients, because the third patient had only been followed up for 3 months at the reporting of the study.29 Pain and Neurological Outcomes Of the 67 patients who presented in pain (95.7% of 70 patients; 9 studies), 100% experienced pain improvement after surgery. Pain improvement was assessed using the visual analog scale (VAS) in 7 studies.10,14,18,20,25,28 The mean preoperative VAS score for patients with cervical spine osteomyelitis ranged from 6.25 to 9 across the 7 studies, and the mean postoperative VAS score ranged from 1.75 to 3.85 (n ¼ 53; 5 studies). The neurological outcomes were assessed using the Frankel grade classification in 5 studies,1,14,15,21,22 the American Spinal Injury Association Impairment Scale (ASIA) in 4 studies,10,11,20,28 and the Nurick grading system in 2 studies.18,25 For the patients assessed using the Frankel scale (n ¼ 23; 3 studies), 16 (70.0%) presented with either motor or sensory neurological deficits, with 2 (8.7%) graded as Frankel A. After treatment, 8 patients (34.7%) had persistent neurological deficits. For the patients assessed using the ASIA (n ¼ 47; 3 studies), 36 (76.6%) presented with either motor or sensory neurological deficits. Preoperatively, most of these patients had been graded as ASIA D (n ¼ 22; 46.8%) or ASIA C (n ¼ 12; 25.5%). No patient had been graded as ASIA A. After surgical treatment and the at last follow-up examination, 33 of the 47 ASIA-graded patients (70.2%) were graded as ASIA E. The remaining 14 patients with a persistent deficit were all graded as ASIA D (29.8%; Figure 2). Hardware Failure and Wound Complications Rates The incidence of hardware failure was 4.6% (n ¼ 10 of 217 patients; 19 of 24 studies). The incidence of wound complications
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was 4.0% (n ¼ 9 of 226 patients; 21 of 24 studies). Hardware failure was defined as reoperation for screw loosening or pull out or graft subsidence. Wound complications and infections were defined as reoperation for wound infection and/or removal of hardware because of continued infection (Tables 4 and 5). Mortality The postoperative mortality rate was 4.1% (n ¼ 8 of 196 patients; 21 of 24 studies).1,6,10-18,21-24,26-30,32 The cause of death was sepsis in 5 patients,11,12 pneumonia in 1 patient,17 complications of malignancy in 1 patient,12 and unspecified in 1 patient (whose history included cardiac insufficiency and chronic alcohol abuse).21 DISCUSSION Cervical spine osteomyelitis poses a challenging management problem for multidisciplinary clinicians in neurosurgery, orthopedic surgery, infectious disease, and internal medicine. We performed a systematic review to assess the pain and neurological outcomes and surgical complication rates for patients who had undergone instrumented fusion, in addition to surgical debridement or decompression. To the best of our knowledge, the present study is the first systematic review of cervical osteomyelitis in >1 decade, and many postoperative outcomes such as neurologic status and hardware revision had not been fully explored.8 Our results suggest low rates of hardware failure and low rates of wound complications in patients with spontaneous pyogenic cervical spondylodiscitis treated with spinal instrumentation. It is important to contextualize the present study within the previous studies investigating the efficacy of surgical management compared with medical management. Comparisons in the previous studies were sparse, however, because although nonoperative management can be attempted first, many surgical candidates constitute those for whom medical therapy has failed and/or who had additional concerning symptoms such as neurologic compression, deformity, or biomechanical instability. In 2015, Alton et al.33 demonstrated a 75% failure rate with medical treatment alone in patients with cervical spinal epidural abscess (18 of 24). They had defined failure as a decline in motor function during intravenous antibiotic therapy.33 Although that study had excluded patients with isolated discitis or osteomyelitis,33 epidural abscesses have been reported to complicate spondylodiscitis at a rate of 90% in the cervical spine (vs. 33.3% in the thoracic spine and 23.6% in the lumbar spine).15 The demographics of the patient population were largely consistent with those from previous reviews, with an average age of 57 years (vs. 57e60 years) and a 64% male predominance (compared with 66%e87%).8 In line with previous reviews,6,8 the major comorbidities identified were diabetes, intravenous drug use, alcohol abuse, and renal insufficiency. Although chronic immunosuppression and distant infections have been frequently cited as risk factors for cervical spine infection, these were infrequently described in the articles included in our study. It is important to consider these results in the context of potential geographic limitations resulting from the inclusion of only English-language articles. Although our review was able to include articles from a range of countries, including China, Korea, Japan,
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Patients Meeting Microbiology S. S. Streptococcus P. M. Criteria (n) Identified (n) aureus (n) epidermidis (n) spp. (n) E. coli (n) aeruginosa (n) tuberculosis (n)
Investigator
Year
Country
Li et al.10
2017
China
14
12
7
1
2
1
0
0
0
10e12
Yesy
D’Souza et al.27
2016
USA
4
4
0
0
0
0
1
0
1 Eikenella; 2 polymicrobial
6
NR
Zhang et al.28
2016
China
24
17
11
4
0
2
0
0
0
3e6
4e10
Bydon et al.19
2014
USA
29
NSz
NA
NA
NA
NA
NA
0
0
NR
NR
4
0
5.5
8.3
0
3
3e9
1 P. acnes
4.2
6
20
Other (n)
IV Oral Antibiotics* Antibiotics* (weeks) (weeks)
Hahn et al.
2014 South Korea
5
4
3
0
0
0
1
Özkan et al.21
2014
Germany
18
NSz
NA
NA
NA
NA
NA
2013
Taiwan
5
5
3
Shousha et al.
2012
Germany
29
NSz
NA
NA
NA
NA
NA
NA
NA
Yesy
8e12
Rayes et al.12
2010
USA
26
22
17
0
1
0
3
0
1 Klebsiella spp.
Yesx
Yesx
Walter et al.
2010
Germany
4
4
4
0
0
0
0
0
0
3
9
Lu et al.24
2009
USA
5
5
5
0
0
0
0
1
0
6
NR
2009
Germany
5
5
5
0
0
0
0
0
0
6
NR
Tsai et al.22 11
23
25
Acosta et al.
2008
USA
4
NR
NA
NA
NA
NA
NA
NA
NA
NR
NR
Suess et al.17
2007
Germany
3
2
1
0
0
0
0
0
1 Proteus mirabilis
4e6
6
2006
USA
2
NR
NA
NA
NA
NA
NA
NA
NA
NR
NR
2006
Greece
3
3
2
1
0
0
0
0
0
4e6
Yesy
Auguste et al.18 14
Korovessis et al. 26
2006
Japan
2
1
1
0
0
0
0
0
0
6e8
8
Dimar et al.31
2004
USA
5
3
3
0
0
0
0
0
0
6
NR
Shad et al.16
2003
UK
5
5
4
1
0
0
0
0
0
12
Yesy
Suchomel et al.29
2003
Czech Republic
3
3
3
0
0
0
0
0
0
3
3
Schimmer et al.1
2002 Switzerland
13
11
7
0
2
2
0
1
1 Klebsiella spp.
NR
NR
Nakase et al.
Hadjipavlou et al.15 2000
USA
6
NS*
NA
NA
NA
NA
NA
NA
NA
6
6
Rezai13
1999
USA
14
NS*
NA
NA
NA
NA
NA
NA
NA
6
Yesy
Zigler et al.31
1987
USA
4
4
3
0
0
0
0
0
1 Pasteurella spp.
2e9
6e72
ORIGINAL ARTICLE
S. aureus, Staphylococcus aureus; S. epidermidis, Staphylococcus epidermidis; E. coli, Escherichia coli; P. aeruginosa, Pseudomonas aeruginosa; M. tuberculosis, Mycobacterium tuberculosis; IV, intravenous; NR, not reported; NS, not specific; NA, not applicable; P. acne, Propionybacterium acnes. *Antibiotic durations reported for nonetuberculosis osteomyelitis. ySpecific duration of treatment not provided. zNot specific for patients meeting review criteria. xAdministered for 6 weeks but route not specified.
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Mondorf et al.
32
1
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Table 2. Patient Microbiology Data and Antibiotic Treatment Duration
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Table 3. Patient Fusion Outcomes and Rates of Hardware Failure and Wound Complications Hardware Failure Investigator
Wound Complications
Year
Country
Fusion Rate (%)
Patients (n)
Total Meeting Criteria (n)
Patients (n)
Total Meeting Criteria (n)
2017
China
100 (14/14)
0
14
0
14
D’Souza et al.
2016
USA
NR
NR
NA
1
4
28
Zhang et al.
2016
China
100 (24/24)
0
24
0
24
Bydon et al.19
2014
USA
NS*
1
29
3
29
Hahn et al.
2014
South Korea
NR
0
9
0
9
Özkan et al.21
2014
Germany
NR
1
18
1
18
2013
Taiwan
100 (5/5)
0
6
1
6
2012
Germany
100 (29/29)
2
29
0
29
2010
USA
NR
0
26
0
26
Walter et al.
2010
Germany
100 (4/4)
0
4
0
4
Lu et al.24
2009
USA
NDy
0
6
0
6
Mondorf et al.
2009
Germany
NDy
1
5
0
5
25
Acosta et al.
2008
USA
100 (4/4)
0
4
0
4
Suess et al.17
2007
Germany
NS*
0
3
0
3
10
Li et al.
27
20
Tsai et al.22 Shousha et al.
11
Rayes et al.12 23
32
18
Auguste et al.
2006
USA
100 (2/2)
0
2
0
2
Korovessis et al.14
2006
Greece
100 (3/3)
0
3
0
3
Nakase et al.26
2006
Japan
100 (2/2)
0
2
0
2
Dimar et al.
2004
USA
NR
NS*
NA
0
5
Shad et al.16
2003
UK
100 (5/5)
0
5
0
5
2003
Czech Republic
66.7 (2/3)z
NR
NA
NR
NA
31
Suchomel et al.29 1
Schimmer et al.
2002
Switzerland
92.9 (13/14)
1
14
2
14
Hadjipavlou et al.15
2000
USA
100 (6/6)
NR
NA
NR
NA
Rezai13
1999
USA
100 (14/14)
4
14
1
14
Zigler et al.31
1987
USA
100 (4/4)
NR
NA
NR
NA
NA
NA
NA
10 (4.6)
217
9 (4.0)
226
Total
NR, not reported; NA, not available; NS, not specific; ND, not done. *Not specific for patients meeting review criteria. yInvestigators were unable to assess for fusion radiographically. zTwo of 3 patients achieved fusion; the third had been followed up for 3 months at the report of the study and had not yet achieved fusion.
Germany, and Greece, these countries do not necessarily represent a diverse sampling of patients with spondylodiscitis and likely represent a publication bias favoring developed countries with more established academic infrastructures for publication. For example, the incidence of tuberculosis varies greatly worldwide, with nearly 50% of all reported cases from Southeast Asia.34 The few cases of instrumented treatment for tuberculosis osteomyelitis described in the present review likely could not capture the full range of potential surgical outcomes. Regarding the bacteriological diagnoses, the rate of culturepositive cases and the predominance of S. aureus were consistent with the vertebral osteomyelitis data elsewhere in the spine.
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Definitive organisms were cultured for 85.4% of patients with cervical spine osteomyelitis compared with 85%e88% of patients with vertebral osteomyelitis in various locations.7,35 Within the vertebral osteomyelitis data, the rate of S. aureus within culture-positive cases has been reported to be 42.7%e57.2%, with 43.8%e49.1% of cases reported to MRSA.35,36 For the cervical osteomyelitis patients, S. aureus was also the most commonly isolated organism. However, S. aureus represented a greater proportion of culture-positive cases of 71.8%, with similar rates of MRSA at 44.0%. The next most frequently isolated organisms were Streptococcus spp. and S. epidermidis. The most commonly isolated gram-negative bacteria were E. coli and P. aeruginosa.
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Figure 2. Preoperative versus postoperative neurological function measured using (Top) American
Our series also examined tubercular infections of the cervical spine. These were relatively uncommon, comprising <3% of our series, which might be expected in the modern era owing to both the declining rates of tubercular infection and the greater propensity of tuberculosis to affect the thoracic spine.37,38 Given their relative rarity in our series, it was difficult to draw too many definitive comparisons with our larger cohort, and dedicated examination of cervical tubercular osteomyelitis might be warranted. However, given M. tuberculosis’ well-documented propensity elsewhere in the spine for anterior column destruction and
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Spinal Injury Association (ASIA) and (Bottom) Frankel grading system.
antibiotic resistance requiring prolonged multidrug treatment regimens, infections from this organism likely represent a distinct pathologic process from other types of cervical bacterial osteomyelitis and warrant special attention to anterior load-sharing and adequate antibiotic compliance. Until recently, the recommended duration of treatment in the vertebral osteomyelitis data had been extrapolated from observational studies and ranged from 4 to 12 weeks.39-43 In the present study, patients with cervical osteomyelitis received intravenous antibiotic treatment for a range of 2 to 12 weeks, with a plurality of
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CERVICAL SPINE OSTEOMYELITIS AND INSTRUMENTED FUSION
Table 4. Reported Hardware Failures Investigator
Year Hardware Failure (n)
Bydon et al.19
2014
1
Hardware failure, NOS
Özkan et al.
2014
1
PMMA implant dislocation
Shousha et al.11 2012
2
Screw dislocations
2009
1
PEEK cage explanted and bone graft inserted at different hospital
Schimmer et al. 2002
1
Hardware failure, NOS
Rezai13
4
1, Screw dislocation/pull out; 2, bone graft extrusion requiring reoperation; 1, graft collapse and screw dislocation
21
32
Mondorf et al.
1
1999
Description
NOS, not otherwise specified; PMMA, poly(methyl methacrylate); PEEK, polyetheretherketone.
studies conforming to the 4e6-week window. In 2015, a randomized controlled trial studying the treatment duration for patients with pyogenic vertebral osteomyelitis demonstrated that 6 weeks of antibiotic treatment is not inferior to 12 weeks, with respect to the cure rate, with 90.9% of the 6-week group and 90. 9% of the 12-week group meeting the criteria for clinical cure at 1 year.44 Although most studies included in the present review continued to treat their patients with oral antibiotics after intravenous administration, no consensus has been reached on the use of oral antibiotics. Individual treatment regimens should always consider a patient’s individual circumstances and the advice from a local infectious disease consultation. Most patients with cervical spine osteomyelitis reported pain on presentation, and the vast majority experienced improvement after surgical debridement and instrumentation. The studies that assessed pain using the VAS demonstrated a decrease in the average VAS score postoperatively, followed by a continued decrease at the last follow-up visit. This finding reaffirms previous findings that surgery can lead to significant improvements in pain. In 1 study comparing surgical and medical management in patients with vertebral osteomyelitis across all levels, 64.3% of the nonsurgically treated group continued to report disabling back pain compared with 26.3% of the surgically treated group.15 Pain persistence in the nonsurgically treated group was often due to kyphosis and pseudarthrosis.15 Although most patients presented with a neurologic deficit (70% using the Frankel grading system and 77% using the ASIA system), few patients presented with a complete deficit. After surgery, approximately one half of the patients in our review were
neurologically intact. Neurological function continued to improve throughout the follow-up period, as evidenced by the 70% patients without neurologic deficit (using the ASIA) at the last follow-up examination. These results confirm that in well-selected patient populations, significant rates of neurologic improvement can be expected postoperatively. This has been mirrored in the thoracolumbar data, with 84%e90% of patients with preoperative deficits reporting improved neurologic status postoperatively.45-47 However, despite the high rates of improvement, these data also highlight the significant morbidity of cervical involvement, with the remaining 30% of patients having persistent neurologic deficits. The present study found a 4.6% reoperation rate for hardware failure and a 4.0% reoperation rate for wound complications. Although instrumentation was performed in an infected space, these rates compare favorably with the data reported from elective degenerative cervical spine cases. Recent large database studies have demonstrated a lower rate of infection for anterior cervical fusion at 0.4%e0.65%48,49 compared with a 3.7% rate associated with posterior cervical fusion.50 In addition, circumferential cervical fusion for noninfectious indications has been associated with a reoperation rate for wound infection of 4.8%e6.7% and for hardware failure of 4.8%.51,52 Our results suggest that despite a priori fears of placing a foreign body in an infected space, the rates of hardware failure and wound infection requiring reoperation might be comparable to other elective cervical spine procedures. Our study had several limitations. First, the primary studies were largely retrospective, and, perhaps by necessity, the patient
Table 5. Reported Wound Complications Investigator
Year
Wound Complication (n)
Description
D’Souza et al.
2016
1
Further decompression and instrumentation for persistent infection
19
Bydon et al.
2014
3
Unspecified reoperation for wound complication
Özkan et al.21
2014
1
Further decompression alone after new abscess development
2013
1
Further decompression and instrumentation for persistent infection
Schimmer et al.
2002
2
1, Hardware removal for persistent infection; 1 tracheostomy and gastrostomy because of deep anterior wound infection
Rezai13
1999
1
Hardware removal for persistent infection
27
22
Tsai et al.
1
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populations were often small and heterogeneous with respect to comorbidities and intraoperative techniques. As such, the present study lacked the statistical power to delineate the optimal surgical management for these patients regarding the approach, surgical technique, graft type, and length of postoperative antibiotics. Another issue was that many studies had broader inclusion criteria than ours (e.g., patients with vertebral osteomyelitis at any location), and we incurred loss of information by including only those subsets of patients relevant to our study. It is possible that excluding studies in this manner incurred a bias. In addition, systematic reviews, by necessity, are influenced by publication bias. This was shown in that the 239 patients isolated in our study represented but a small fraction of the overall incidence of cervical osteomyelitis during the >30-year period reviewed in our series. We attempted to limit the effect of publication bias by excluding single-patient case studies. Nevertheless, a distinct possibility remains that the reported results have underestimated the true
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Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 15 June 2018; accepted 16 August 2018 Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.08.129 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com
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