Vertebral osteomyelitis is estimated to affect 2.4 per 100,000 individuals each year.1 The overall incidence of this disease is increasing, particularly within the elderly male population,2 and it has an estimated 1-year cumulative mortality rate of 11%.3 The clinical manifestations typically include localized bone pain, decreased range of motion, draining sinus tracts, fever, irritability, and lethargy.4 Vertebral osteomyelitis is also highly associated with neurological manifestations, including radiculopathy, motor weakness, sensory loss, and urinary retention. Overall, these neurological complications appear in 34% of patients with vertebral osteomyelitis.5–8
Vertebral osteomyelitis can be categorized into monomicrobial vertebral osteomyelitis and polymicrobial vertebral osteomyelitis. The majority of cases of vertebral osteomyelitis are monomicrobial, with Staphylococcus aureus constituting approximately 48% of these cases.5,9–12 Other organisms that may be isolated in monomicrobial vertebral osteomyelitis include Escherichia coli (11.8%), Streptococcus species (9.4%), coagulase-negative staphylococci (6.7%), Pseudomonas aeruginosa (5.1%), Klebsiella species (2.0%), Proteus mirabilis (2.0%), and Salmonella species (1.6%).3 Polymicrobial infections are less common and are estimated to account for 8% of all cases of vertebral osteomyelitis. There is a limited amount of literature surrounding polymicrobial vertebral osteomyelitis and how it may differ clinically from monomicrobial vertebral osteomyelitis. Such research may be useful not only in delineating differences in clinical outcomes but perhaps also prompting modification of the management of polymicrobial vertebral osteomyelitis.
The purpose of this study was to compare the clinical outcomes between monomicrobial and polymicrobial vertebral osteomyelitis infections. Specifically, the authors compared (1) various demographic metrics, including mean age, gender, infection size, and vertebral instability; (2) mortality rate; (3) clearance of infection; (4) clinical outcomes measured by the Oswestry Disability Index; and (5) mean length of stay between the 2 cohorts. The authors hypothesized that polymicrobial infections may be associated with more inferior clinical outcomes.
Materials and Methods
Institutional review board approval was obtained for this study. The database of all patients who were treated for vertebral osteomyelitis from 2001 to 2011 at the authors' institution was reviewed. Patients were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes, which included osteomyelitis (730.28, 730.08, 730.2, 730.00), diskitis (722.90, 722.91, 722.92, 722.93), and epidural abscess (324.1 and 234.9) of the spine. Inclusion criteria were presence of appropriate initial imaging, including both computed tomography and magnetic resonance imaging of the spine; complete laboratory workup, including erythrocyte sedimentation rate; availability of microbial culture and gram stains from biopsy results; and no previous medical or surgical treatments for vertebral osteomyelitis. Seventy-nine patients met the inclusion criteria specifically for the management of vertebral osteomyelitis. This included 45 men (57%) and 34 women (43%) who had a mean age of 60 years (range, 18 to 85 years) and who were followed for a mean of 50 months (range, 24 to 75 months). All inpatient and outpatient clinic charts including the radiographic information were reviewed.
Patients were divided into the monomicrobial vertebral osteomyelitis or the polymicrobial vertebral osteomyelitis group based on the results of microbial culture and gram stain obtained from the biopsy. Magnetic resonance imaging was used to calculate the volume of infections. The size of infection was defined as the total volume of infected bone and soft tissues measured on coronal, sagittal, and axial magnetic resonance imaging sequences and by multiplying the length, width, and height of the total area of infection. Instability was defined as the presence of a greater degree of abnormal motion between vertebrae based on imaging.
All patients were followed at approximately 6 weeks, 3 months, and then annually. During each visit, patients were examined thoroughly and Oswestry Disability Index score was recorded. Clearance of the infection was defined as normalization of the serum markers and resolution of the osteomyelitis on magnetic resonance imaging after 6 months of treatment.
An Excel spreadsheet (Microsoft Corporation, Redmond, Washington) was used to record all data. Patient demographics, infection size, erythrocyte sedimentation rate, Oswestry Disability Index score, vertebral instability, length of hospital stay, clearance rate, and mortality rate were compared between the 2 cohorts using the chi-square test, Fisher's exact test, odds ratio, and the Student's t test. P=.05 was used as the threshold for statistical significance.
Twenty-six patients (32.9%) had a polymicrobial infection on presentation and 53 (67.1%) did not. There were no significant differences in the proportions of male and female patients between the polymicrobial group (15 male) and the monomicrobial group (30 male); however, the polymicrobial group was significantly older than the monomicrobial group (mean age of 63 years [range, 29 to 93 years] vs mean age of 59.5 years [range, 21 to 89 years]; P=.03).
Polymicrobial infections were associated with significantly larger areas of infection than were monomicrobial infections (26,142 mm3 vs 11,251 mm3; P=.02). Erythrocyte sedimentation rate was also significantly more elevated in polymicrobial infections than in monomicrobial infections (88 vs 75 mm/h; P=.013). Patients with polymicrobial infections had significantly more vertebral instability than patients with monomicrobial infections (42.3% vs 20.7%; odds ratio, 2.6; P=.01).
Polymicrobial infections had a significantly higher mortality rate than monomicrobial infections (19.2% vs 9.4%; odds ratio, 2.40; P=.0461). Five of the 26 polymicrobial infections led to death, compared with 5 of the 53 monomicrobial infections (P=.04).
Polymicrobial infections had a lower rate of clearance of infection compared with monomicrobial infections, and this trended toward significance (42.3% vs 56.6%; odds ratio, 0.60; P=.0899). Also, polymicrobial infections were associated with significantly longer hospital stays than monomicrobial infections (30.4 days vs 19 days; P=.003).
There were no significant differences in Oswestry Disability Index scores between the 2 cohorts at final follow-up. In the polymicrobial cohort, the mean Oswestry Disability Index score had improved from 72 points (range, 64 to 78 points) to 29 points (range, 25 to 36 points). The monomicrobial cohort similarly improved, from 68 points (range, 59 to 76 points) to 28 points (range, 24 to 38 points).
Vertebral osteomyelitis, which can be fatal, may be categorized into monomicrobial and polymicrobial infections. Currently, little literature exists comparing clinical outcomes between these 2 types of infection. In this study, the authors attempted to assess the clinical differences between these 2 presentations. Polymicrobial vertebral osteomyelitis infections were associated with larger infection, higher presenting erythrocyte sedimentation rate, higher mortality rate, and lower clearance of infection.
This study found that the mortality associated with both monomicrobial vertebral osteomyelitis and polymicrobial vertebral osteomyelitis was higher than previously reported. Akiyama et al,13 when retrospectively examining 7118 patients with vertebral osteomyelitis, found an in-hospital mortality rate of 6%. In their study, 58.9% of the patients were men and the average age was 69.2 years. There was a linear trend between higher rates of in-hospital mortality and older age, need for hemodialysis, diabetes, liver cirrhosis, malignancy, and infective endocarditis. Bhavan et al,14 when retrospectively examining 70 patients with vertebral osteomyelitis, found an in-hospital mortality rate of 4%. In their study, the mean age of the patients was 59.7 years (±15.0 years) and 38 (54%) were male. Common comorbidities included diabetes (43%) and renal insufficiency (24%).
Overall, polymicrobial vertebral osteomyelitis infections were associated with lower clearance rates when compared with monomicrobial vertebral osteomyelitis infections. This may suggest that individuals with polymicrobial infections are more likely to follow a chronic or unremitting course rather than recover after hospital therapy. However, the clearance rate in the current study was less than previously reported rates. McHenry et al,3 when retrospectively examining 173 patients with vertebral osteomyelitis, found that recovery was reached by approximately 89%. In another study, long-term recovery rates were reported to be 88% or 83%, depending on whether antibiotics were administered for up to 6 weeks or for more than 6 weeks, respectively.15 These rates are greater than the polymicrobial vertebral osteomyelitis recovery rate (31.9%) and the monomicrobial vertebral osteomyelitis recovery rate (58.5%) reported in the current study. Nonetheless, polymicrobial vertebral osteomyelitis infections had significantly lower recovery rates compared with monomicrobial vertebral osteomyelitis infections, which may represent a more virulent or resistant infectious process.
The relationship between polymicrobial vertebral osteomyelitis and increased vertebral instability is also clinically relevant in the management of vertebral osteomyelitis. Prior literature suggests that spinal instability is an important cause of lower back pain and neurological dysfunction.16 It is not uncommon for individuals with spinal instability to experience significant functional disability, including pain with mobilization and a sense of vulnerability with movements in the spinal neutral zone.17 In some instances, highly deforming lesions that result in significant spinal instability are reason enough for surgical intervention.12,18 Thus, the greater vertebral instability seen in polymicrobial vertebral osteomyelitis infections should raise concern for the increased risk of back pain and sciatica, as indicated in prior literature.19
In the current study, Oswestry Disability Index scores did not differ significantly between monomicrobial vertebral osteomyelitis and polymicrobial vertebral osteomyelitis infections. Oswestry Disability Index scores have previously been used as a tool to assess the degree of functional impairment following vertebral osteomyelitis.20 Oswestry Disability Index scores have been shown to be an accurate measurement of limitation in activities of daily living.21 A score less than 20 may rule out spondylitis, whereas increasingly higher scores are associated with greater degrees of disability. The authors found that there was no difference in Oswestry Disability Index scores between the 2 groups.
Finally, polymicrobial vertebral osteomyelitis infections are associated with higher erythrocyte sedimentation rates than monomicrobial vertebral osteomyelitis infections. Prior studies have shown that an elevated erythrocyte sedimentation rate at the time of admission is 94% sensitive (95% confidence interval, 90%–96%) in predicting all causes of osteoarticular infections.22 Vertebral osteomyelitis, in particular, is found to have an elevated erythrocyte sedimentation rate in 98% of affected patients.23 The degree to which erythrocyte sedimentation rate is elevated and its relationship to the severity of infection may not be entirely clear, however. In a retrospective study, Chelsom and Solberg9 assessed the laboratory findings of 40 patients with vertebral osteomyelitis and reported a mean erythrocyte sedimentation rate of 79±26.8 mm/h. Similar studies have reported mean erythrocyte sedimentation rates ranging from 58.5 to 81 mm/h.18,24 In the current study, polymicrobial infections had a mean erythrocyte sedimentation rate above that reported in previous studies, whereas monomicrobial infections had a mean erythrocyte sedimentation rate close to prior reported values. Thus, an unusually high erythrocyte sedimentation rate may be indicative of polymicrobial osteomyelitis and should serve to heighten awareness to possible complications associated with such infections.
The current study had several limitations. First, the sample size was limited as a result of the inclusion criteria required to fully evaluate clinical outcomes. Given the retrospective nature of this study, another limitation may have been the relative lack of standardization in management, although all patients were treated in consultation with infectious disease physicians. Some patients had required surgical interventions, but this was not assessed in this study. Finally, results were not stratified by comorbid conditions, which may have predisposed patients to certain microbiological organisms or impaired immune responses, thus altering the clinical outcomes. Despite these limitations, the authors believe this study was effective in fulfilling its original purpose and adds to the body of literature regarding polymicrobial vertebral osteomyelitis.
Polymicrobial infections were associated with greater morbidity and mortality than monomicrobial infections. Polymicrobial infections were also associated with a significantly larger area of infection, lower clearance of infection, higher erythrocyte sedimentation rate, longer hospital stay, greater degree of vertebral instability, and greater mortality. The mechanism of such has yet to be elucidated, but likely involves the additive virulence of multiple organisms and the presence of permissive conditions, such as comorbid disorders, which enables bacteria to destroy healthy tissue. Patients with polymicrobial infections may benefit from counselling regarding potentially more inferior treatment outcomes.
- Grammatico L, Baron S, Rusch E, et al. Epidemiology of vertebral osteomyelitis (VO) in France: analysis of hospital-discharge data 2002–2003. Epidemiol Infect. 2008; 136(5): 653–660. doi:10.1017/S0950268807008850 [CrossRef]
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- Issa K, Pourtaheri S, Vijapura A, et al. Delay in diagnosis of vertebral osteomyelitis affects the utility of cultures [Epub ahead of print]. Surg Technol Int. 2016.
- Pourtaheri S, Issa K, Stewart T, et al. Comparison of instrumented and noninstrumented surgical treatment of severe vertebral osteomyelitis. Orthopedics. 2016; 39(3):e504–e508. doi:10.3928/01477447-20160427-07 [CrossRef]
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