Pyogenic Vertebral Osteomyelitis: A Systematic Review of Clinical Characteristics

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Pyogenic Vertebral Osteomyelitis: A Systematic Review of Clinical Characteristics E. Mylona, MD, M. Samarkos, E. Kakalou, P. Fanourgiakis, and A. Skoutelis

Objectives: Vertebral osteomyelitis is a cause of back pain that can lead to neurologic deficits if not diagnosed in time and effectively treated. The objective of this study was to systematically review the clinical characteristics of pyogenic vertebral osteomyelitis (PVO). Methods: The authors conducted a systematic review of the English literature. The inclusion criteria included studies with 10 or more subjects diagnosed with PVO based on the combination of clinical presentation with either a definitive bacteriologic diagnosis or pathological and/or imaging studies. Results: The 14 studies that met selection criteria included 1008 patients with PVO. Of them, the majority (62%) were men, with back pain and fever as the most common presenting symptoms. Diabetes mellitus was the most common underlying medical illness, while the urinary tract was the commonest source of infection. Staphylococcus aureus was the most commonly isolated organism. Computed tomographic guided or open biopsy yielded the causative organism more often than blood cultures (77% versus 58%). Plain radiography showed abnormalities in 89% of the cases, while bone scanning and computed tomography or magnetic resonance imaging were positive in 94% of the cases, revealing lumbar as the most commonly affected area. The attributable mortality was 6%, while relapses and neurological deficits were described in the 32% and 32% of the cases, respectively. Conclusion: PVO is an illness of middle-aged individuals with underlying medical illnesses. Although the mortality rate is low, relapses and neurological deficits are common, making early diagnosis a major challenge for the physician. © 2008 Elsevier Inc. All rights reserved. Semin Arthritis Rheum xx:xxx Keywords: vertebral osteomyelitis, discitis, spondylitis, pyogenic

V

ertebral osteomyelitis accounts for about 1% of skeletal infections. Its incidence, however, seems to be increasing as a result of the higher life expectancy of older patients with chronic debilitating diseases, the rise in the prevalence of intravenous drug abuse, and the increase in spinal instrumentation and surgery (1). In adults, it usually presents insidiously and follows an indolent clinical course, making early diagnosis difficult. The symptoms and clinical findings of patients are often nonspecific and may vary widely, thus making imaging necessary for confirmation and localization of the infection (2,3). Bacteriological diagnosis is also difficult, since blood cultures are often negative and bone biopsy is

5th Department of Medicine and Infectious Diseases Unit, Evangelismos General Hospital, Athens, Greece. Address reprint requests to E. Mylona, MD, 5th Department of Medicine, Evangelismos Hospital, 45-47 Hipsilantou Str., Kolonaki, GR-106 76 Athens, Greece. E-mail: [email protected].

0049-0172/08/$-see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.semarthrit.2008.03.002

required. While life expectancy may not be affected, neurologic compromise can occur when diagnosis and treatment are delayed (4). Therefore, physicians must be able to recognize this entity, since its prompt and accurate diagnosis depends on a thorough knowledge of the disease along with a high index of suspicion. In the last 20 years, several reported series have analyzed the clinical, microbiological, and radiologic features of vertebral osteomyelitis. However, some of them have focused on a particular etiologic agent (5,6), age group (7), treatment method (8), or radiologic technique (9). As a result, certain clinical, diagnostic, and therapeutic issues remain unclarified. To date, there has been no comprehensive review of the literature on pyogenic vertebral osteomyelitis (PVO) to help in clarifying the epidemiology, clinical, microbiological, and diagnostic issues as well as the outcome of PVO in the general population. We systematically reviewed the literature on PVO. The primary objectives of this study were to review the epidemiology 1

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and the clinical and microbiological aspects of the disease, to evaluate the diagnostic methodology, and to assess the parameters related to the outcome. METHODS Literature Search We collected the literature by searching the MEDLINE database starting with 1966. We also used textbooks of infectious diseases and orthopedics. The MEDLINE search string was “Discitis”[Mesh] OR “vertebral osteomyelitis” OR “spinal osteomyelitis” OR spondylodiscitis OR spondylitis NOT ankylosing NOT “case reports” [pt]. The results were limited to human studies published in the English language. Manual searches of reference lists from potentially relevant papers and book chapters were also performed to identify any additional studies that may have been missed using the computer-assisted method. The literature search yielded 1663 articles that were imported to a database using Reference Manager Professional Edition v10 (ISI Research Software). We screened the abstracts of these articles and retrieved the full text of the ones we considered important. After detailed review, 38 items were identified as potentially relevant, but only 14 of them fulfilled the inclusion criteria.

Pyogenic vertebral osteomyelitis

RESULTS Study Characteristics and Limitations Epidemiological, clinical, and microbiological aspects of PVO require careful interpretation for 2 reasons: (a) there is heterogeneity of the inclusion criteria among studies. Thus, 2 reports (10,19) excluded drug abusers and 5 (10,12,16,21,23) excluded postoperative infections. On the contrary, in 1 report (14) intravenous drug abusers constituted the majority of the included patients. (b) Almost all the studies (93%) are retrospective, in which there is a potential for error because of bias and statistical inaccuracy. For example, PVO caused by low virulence organisms may have been underestimated because such organisms could have been discarded as contaminants. Demographic Data One thousand eight patients were included in the 14 studies. The mean age of the patients ranged from 46 to 72 years (median value, 59 years) (10,11,15-20,22,23). The 2 studies that included many drug users reported the lowest ages (mean and median values, 46 and 35 years, respectively) (14,23). Demographic characteristics are shown in Table 1. Underlying Medical Illnesses

Study Selection Criteria Two investigators independently reviewed the titles and abstracts of all citations identified by the literature search and evaluated them for eligibility on the basis of some inclusion criteria. In the studies included in our review, the diagnosis of PVO had to be based on the combination of clinical presentation with either a definitive bacteriologic diagnosis or pathological and/or imaging studies. Moreover, they had to involve 10 or more subjects diagnosed with vertebral osteomyelitis. Studies including only patients with tuberculosis or brucellosis were excluded. Studies involving only a specific population, only a particular treatment, or only a specific pathogen were also excluded. Studies including patients with history of intravenous drug abuse and prior spinal instrumentation or surgery were included.

All studies reviewed revealed information about the possible concomitant diseases of their patients (Table 1). However, Patzakis and coworkers focused solely on drug users (14). Most patients were reported to have more than 1 underlying medical illness, including diabetes mellitus (24%), intravenous drug abuse (11%), immunosuppression (7%), malignancy (6%), alcoholism (5%), rheumatic disease (5%), liver cirrhosis (4%), renal failure (4%), and previous deficit of the vertebrae such as radiation or osteopenic fracture (3%). Other underlying medical illnesses such as pulmonary fibrosis, predisposing heart conditions, malnutrition, myelodysplasia, sarcoidosis, septic phlebitis, or partial gastrectomy, occurred in 10% of the patients. Only 1 (17) of 14 studies states that 28% of its patients had no underlying medical illness.

Data Extraction

Clinical Presentation

Two reviewers extracted the data independently. Any disagreement was resolved by consensus. The reviewers extracted the following data from each study: number of subjects, age, mean time from onset to diagnosis, the prevalence of fever, neurological symptoms or deficits at presentation, source of infection, concomitant diseases/risk factors, causative organisms, material of which the microorganisms were isolated (blood, tissue), location of infection, other foci of infection, imaging studies performed and their ability to identify vertebral defect, the outcome, and the proportion of surgically treated patients. For numerical variables we calculated means, taking into account the number of subjects in each study.

The mean time from onset of symptoms to diagnosis was reported in 5 studies and ranged from 11 to 59 days (10,11,18-20). Back pain was by far the most common presenting symptom (86%), followed by fever (axillary temperature ⬎37.5°C), found in the 60% of the cases. Neurologic deficits at presentation, such as radiculopathy, limb weakness or paralysis, dysesthesia or sensory loss, and retention of urine was reported in 34% of patients (1013,15,16,18-23) (Table 1). Bacteriologic Evaluation All reports identified a causative organism of PVO in the majority of their patients (range, 67-100%). In 85% of

E. Mylona et al.

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them a single organism was isolated (10-23), while polymicrobial infection was reported in the 9% of the cases included in the reviewed studies (10-20,23). The prevalence of the various bacteria is shown in Table 2. The prevalence of Gram-positive bacteria ranged from 26 to 93%, while Gram-negative bacilli were reported to be isolated less often (range, 5-56%). Overall, Staphylococcus aureus was the most commonly isolated organism, accounting for 32 to 67%, followed by Streptococcus species (range, 0-24). Patzakis and coworkers, having included a large number of intravenous drug users (78%) in their report, found a relatively low prevalence of S. aureus as a causative organism (17%), while Pseudomonas aeruginosa was the predominant etiologic agent (38%) (14). On the contrary, Carragee reported 11 of 15 of the intravenous drug users included in his study to be positive for S. aureus and only 1 with remote or suspected history of drug abuse to yield P. aeruginosa (16). Diagnostic tools for bacteriologic diagnosis included blood cultures, computerized tomography (CT)-guided needle biopsy or aspiration, and open biopsy. Eighty percent of the reviewed studies reported detailed information concerning the diagnostic procedures and the number of positive ones (10-15,17-22). Blood cultures were performed rather frequently (91%; range, 43-100%) with a reported yield of 58% (range, 30-78%), while biopsy (CT-guided and open) was performed in 79%, ranging from 48 to 100%, providing a better yield (77%, range, 47-100%) (Table 2). The source of infection was documented in 53% of the cases in 9 of 14 reviewed studied (10-12,16-20,22). However, details were given only for 35% of the cases. Urinary tract was the most frequently presumed source of infection (17%) (Table 1). The source of infection is clearly characterized as unknown in 5 of the 14 studies, representing the 32% of the reported cases, while no data are given for the remaining 18% of the cases. In addition, extravertebral foci of infection were described. Among them, endocarditis accounted for 12% of the reported cases (10,12,14,17,20,21) and meningitis for 4% (1214). Paraspinal or epidural abscesses were reported in 44% of the cases (10,12,13,15). Vertebral Level Involved Twelve studies described the vertebrae involved (Table 2); however, details are not given regarding the vertebral levels affected in cases with single versus multiple vertebral levels involved. The lumbar area was affected in 58% of the patients included in the respective studies, followed by the thoracic (30%) and cervical area (11%) (10-17,1923). Twelve of the above studies reported that some patients presented with vertebral defects in multiple levels, accounting for 4% (10-12,14,15-17,19-23), while only 5 indicated the continuous (6%) or the skipping (3%) character of the multifocal involvement (10,13,14,19,22). The highest rate of multifocal involvement was observed

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(68%) by Patzakis and coworkers, whose study included the greatest number of intravenous drug abusers (14). However, multifocal involvement was also reported in non-drug users, although in low frequency (3-15%) (1,6,10,12,15). Imaging Studies Forty percent of the studies described the radiological techniques performed, including plain radiography, bone scanning, CT, and magnetic resonance imaging (MRI) (10,14,18-21) (Table 2). Although abnormalities on plain radiographs generally occur several weeks after the onset of the infection, plain radiography seems to be regarded as a baseline examination, almost always performed (95%) and revealing abnormalities in the 89% of the cases. Bone scanning was performed with a frequency ranging from 28 to 90% (58%), and was positive in 94% of the cases. CTs and MRIs were not always performed (range, 0-95% and 0-100%, respectively) but when performed almost always provided findings consistent with infection (94 and 94%, respectively), including vertebral and/or disc destruction and epidural and/or paravertebral abscesses. Treatment and Follow-Up All 1008 patients included in the reviewed studies received antibiotic treatment for their PVO. However, many (48%) were also subjected to surgical treatment for various indications. Indications for surgery, other than biopsy, included spinal stabilization (23%), drainage of abscesses (21%), relief of compression (13%), correction of postinfection deformity (2%), and various others such as debridement, excision of sinuses, removal of infected hardware, resection of infected aneurysms, or grafts (2%) (data not shown). The mortality rate was 6% (10-16,1822), while relapses were described in 32% of the cases (10-14,19,20,23) (Table 2). Most deaths were due to S. aureus sepsis, despite appropriate antibiotic treatment (10,12,14,19). Although the survival of PVO was generally good, functional outcome was poorer, since 27% of the patients had complications that seriously affected their quality of life. Only 6 of the reviewed studies described in detail the complications of their patients, which included persistent pain (28%), motor weakness or paresis (16%), and bowel or bladder dysfunction (7%) (data from individual studies not shown). In some patients more than 1 complication was present (10,13,16,19,21,23). As far as the functional outcome of surgical treatment is concerned, of the 2 studies reporting data on that particular point (total of 128 patients), the majority (80%) had a favorable outcome (ie, the patients improved or regained their function), while in 20% functional status remained unchanged or deteriorated (13,20). Only 1 study compared the functional outcome between nonsurgically and surgically treated patients, reporting that in the first group 64% of the patients experienced

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Pyogenic vertebral osteomyelitis

Table 1 Clinical Characteristics of PVO in the Reviewed Studies Characteristics No. of patients studied Male gender Age (mean) y Time from symptom onset to diagnosis (mean, days) Symptom at onset Back pain Fever Neurologic impairment Underlying illnesses Diabetes Drug abuse Immunosuppression Malignancy Alcohol abuse Rheumatic disease Cirrhosis Renal failure Vertebral deficit Othera No risk factor Source of infection Skin Respiratory/sinusitis Oral Catheters (iv/shunt) Urinary tract GI tract Osteoarticular Unknown Other foci of infection Endocarditis Meningitis Abscesses

Nolla et al (10)

Colmenero et al (11)

Pigrau et al (12)

McHenry et al (13)

Patzakis et al (14)

Zarrouk et al (15)

Carragee et al (16)

64 36 59 48

72 51 50 50

91 64 NR NR

253 160 NR NR

61 49 NR NR

29 17 58 NR

111 67 60 NR

64 51 18 29 18 0 0 2 0 1 6 5 0 1 NR 30 2 0 0 2 13 6 0 7

67 54 29 NR 17 9 5 5 4 2 3 1 NR 4 NR 42 15 0 0 0 11 4 3 0

88 73 27 NR 29 4 11 NR 0 NR 12 4 NR 10 NR 15 0 2 8 14 5 0 47

NR 197 62 201 79 10 0 10 29 10 10 10 0 43 NR 130 NR NR NR NR NR NR NR NR

NR NR NR NR NR 48 NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR NR

29 16 15 NR 6 NR NR NR NR NR 3 NR NR NR NR NR NR NR NR NR NR NR NR NR

101 18 39 NR 28 0 29 22 0 9 3 3 13 2 NR 86 NR NR NR NR 34 NR NR NR

4 NR 39

NR NR NR

28 8 34

NR 7 122

1 1 NR

NR NR 17

NR NR NR

PVO, pyogenic vertebral osteomyelitis; NR, nonreported. aIn the group of other underlying illnesses, pulmonary fibrosis, heat injuries, predisposing heart conditions, malnutrition, myelodysplasia, sarcoidosis, total gastrectomy, and septic phlebitis are included. bNumber of patients with positive finding to the number of patients studied.

disabling pain or relapse of their PVO versus 26% in the second group (23). DISCUSSION We performed a systematic review of all PVO studies and identified 14 retrospective studies, including 1008 patients with PVO and excluding patients with tuberculosis and brucellosis. Based on these studies, we tried to clarify demographic, clinical, and microbiological characteristics of the disease, the contribution of various diagnostic procedures, and imaging studies to the etiological diagnosis of the disease, with particular attention to patient outcome. PVO was found to affect mainly men with underlying medical illnesses. Conditions predisposing to PVO were diabetes mellitus, ethanol abuse, renal and hepatic failure, malignancy, and immunosuppression. Intravenous drug abuse was a significant risk factor affecting younger people.

The clinical picture of PVO often was nonspecific. Back pain was by far the most common presenting symptom. Notably, fever was often absent at presentation, thus distracting the clinician from the possibility of infection and delaying the diagnosis (mean time to diagnosis, 11-59 days). Neurologic deficits at presentation helped in earlier diagnosis. Since the symptoms and clinical findings of PVO are often nonspecific, imaging is an essential part of the diagnostic workup. Plain radiographic changes often take weeks to months to appear. The earliest radiographic sign may be an ill-defined vertebral endplate. Enlargement of perivertebral soft tissues may also be detected in association with bony impairment (3). Bone nuclear scans have high sensitivity but low specificity and may be useful in diagnosing early vertebral involvement in patients with normal plain radiography. Moreover, they can be considerably helpful when multiple, noncontiguous vertebrae

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Table 1 Continued Ledermann et al (17)

Bateman et al (18)

Torda et al (19)

Osenbach et al (20)

Chelsom et al (21)

Nather et al (22)

Hadjipavlou et al (23)

46 24 58 NR NR NR NR NR 7 6 2 0 0 5 0 0 NR 7 13 NR 1 NR NR NR 1 NR NR NR

66

40 32 60 42

40 21 NR NR

14 12 62.5 NR

101 76 46 NR

1008 628/1008 (62)

62 59

20 19 72 11

66 16 26 NR 11 1 NR NR 3 5 NR 3 12 NR NR 19 2 1 2 0 4 0 0 NR

17 6 14 NR 0 0 2 NR NR NR NR NR NR NR NR 20 NR 0 1 8 3 1 0 2

39 20 19 18 8 2 0 0 7 1 0 0 0 NR NR 27 10 5 1 0 6 0 2 6

40 26 19 17 4 2 4 0 0 3 0 0 0 4 23 19 NR NR NR NR NR NR NR NR

14 4 2 7 5 1 0 1 0 0 0 1 0 5 7 NR NR NR NR 1 1 1 NR NR

NR NR 40 NR 14 25 8 8 NR 1 10 8 NR 1 26 30 NR NR NR NR NR NR NR NR

525/608 (86) 481/800 (60) 310/901 (34) 226/947 (24) 108/979 (11) 61/832 (7) 48/741 (6) 43/797 (5) 37/807 (5) 47/861 (5) 35/898 (4) 25/788 (3) 77/792 (10) 69/898 (9) 403/767 (53) 45/397 (11) 6/353 (2) 6/353 (2) 19/367 (5) 87/524 (17) 17/367 (5) 5/353 (1) 62/287 (22)

NR NR NR

1 NR NR

3 NR NR

2 NR NR

NR NR NR

NR NR 27

43/362 (12) 16/405 (4) 239/538 (44)

4 NR NR

are involved (24). CT and MRI have significantly improved the sensitivity and specificity over simple radiography in the diagnosis of PVO. CT is the study of choice for the detailed assessment of bone destruction and the detection of the exact position of sequestrum (3), while MRI is currently the imaging procedure of choice to detect early infection and to fully evaluate the extent of disease affecting the spine, delineating soft tissue, neural structures, and formed abscesses (3). The use of gandolinium may enhance changes in equivocal cases (25). Based on imaging techniques, the lumbar area was the most frequently affected followed by thoracic and cervical area. Multiple levels of involvement were observed in both drug and non-drug users, though more rarely in the second group. When multiple levels were involved, the continuous form of involvement was observed more often. In all cases of PVO a specific microbiologic diagnosis is highly desirable for susceptibility testing-guided antibi-

Sumb (%)

otic treatment. However, etiological diagnosis was not always feasible. Blood cultures resulted in the isolation of the pathogen in 58% of the patients from whom they were obtained. In the absence of positive blood cultures or when patients were not responding favorably to treatment, biopsy (CT-guided or open) was undertaken, providing a yield in 79% of the cases. Moreover, biopsy is necessary when a polymicrobial infection is suspected, since blood cultures often yield only 1 organism (13). In clinical practice, empirical antibiotic therapy usually is commenced based on clinical and radiological findings, despite the absence of a microbiological diagnosis, a strategy which undoubtedly contributes to the low yield of cultures. However, recently published recommendations suggest that antimicrobial treatment should not be started until the organism is identified, unless clinical circumstances such as serious as neutropenia or severe sepsis dictate otherwise (26).

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Pyogenic vertebral osteomyelitis

Table 2 Location, Microbiological Characteristics, Diagnostic Studies, and Outcome of PVO in the Reviewed Studies Characteristics No. patients studied Location Vertebral levels involveda Cervical Thoracic Lumbar Sacral Multiple vertebrae Continuous Skipping Imaging studies performed Plain radiograph Bone scan CT MRI Imaging studies positive Plain radiograph Bone scan CT MRI Blood cultures positive Biopsy/aspirate positive Microbiology Monomicrobial Polymicrobial Gram positive S. aureus MRSA S. epidermidis Streptococcus spp Enterococcus Gram negative E. coli Proteus Klebsiella Pseudomonas Candida/Aspergilus No organism Outcome Relapse Death Complications Surgery

Nolla et al (10)

Colmenero et al (11)

Pigrau et al (12)

McHenry et al (13)

Patzakis et al (14)

Zarrouk et al (15)

Carragee et al (16)

64

72

91

253

61

29

111

65 5 18 42 0 3 2 1

72 8 19 45 0 0 0 0

85 14 21 50 0 6b NR NR

255 28 77 149 1 NR NR 7

58c 8 6 44 0 11 NR NR

33 5 8 20 0 4 NR NR

145 0 67 58 0 11 NR NR

64 53 36 33

NR NR NR NR

NR NR NR NR

NR NR NR 110

61 25 NR NR

NR NR NR 29

NR NR NR NR

57 51 36 33 46/64 26/41

NR NR NR NR 23/55 31/43

NR NR NR NR 71/91 NR

NR NR NR 81 156/255 174/237

60 25 NR NR 13/26 60/60

NR NR NR 29 14/29 15/19

NR NR NR NR 66/111 55/55

64 0 37 22 1 2 12 1 25 15 3 0 3 0 0

69 3 40 29 0 9 0 0 18 8 2 0 7 5 0

91 0 66 37 0 3 24 0 21 14 0 0 1 3 0

235 20 164 123 0 17 24 0 59 30 5 5 13 0 0

51 10 16 12 0 3 1 0 34 2 0 6 23 1 0

25 4 NR 15 NR NR 7 NR NR NR NR NR NR NR 0

99 12 76 40 0 18 18 0 9 7 0 0 1 1 9

3 2 37 24

4 2 29 33

3 5 22 12

36 29 NR 109

2 1 4 3

NR 1 6 NR

NR 3 NR 42

aThe

numbers refer to location by episode, not by patient. the total number of vertebral levels involved, the 6 cases of multiple locations are not included. cThe respective authors give data for less patients than those included in their studies. dNumber of patients with positive finding to number of patients studied. bIn

Overall, S. aureus was the most commonly isolated organism, while among Gram-negative bacilli, Escherichia coli, was the predominant etiological agent. Other organisms isolated were Staphylococcus epidermidis, Streptococcus species, Streptococcus pneumoniae, Enterococcus and Klebsiella species, Proteus mirabilis, anaerobes, Candida, and Aspergilus spp. The microbiology of PVO in drug users is an issue which remains to be clarified as both P. aeruginosa (14) and S. aureus have been isolated from the majority of

patients in various studies (16). PVO due to S. epidermidis is a frequent isolate in patients with previous spinal surgery as well as in elderly and immunocompromised patients (13,16,23). Therefore, one should be cautious before considering S. epidermidis as a contaminant in the above group of patients. Unlike S. epidermidis, the epidemiology of methicillin-resistant S. aureus is always a nosocomial infection. Community-acquired methicillin-resistant S. aureus was never isolated.

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Table 2 Continued Ledermann et al (17)

Bateman et al (18)

Torda et al (19)

Osenbach et al (20)

Chelsom et al (21)

Nather et al (22)

Hadjipavlou et al (23)

Sumd (%)

46

66

20

40

40

14

101

1008

46 12 10 24 0 0 0 0

NR NR NR NR NR NR NR

20 3 8 9 0 0 0 0

40 12 11 17 0 0 0 0

42 4 14 24 0 2 NR NR

14 1 3 6 0 4 3 1

98c 10 33 55 0 0 0 0

817 110/973 (11) 295/973 (30) 563/973 (58) 1/973 (0.1) 35/942 (4) 5/78 (6) 9/333 (3)

NR NR NR 46

56 47 36 7

20 18 19 5

40 8 21 14

36 19 32 23

NR NR NR NR

NR NR NR NR

277/291 (95) 170/291 (58) 144/230 (63) 267/558 (48)

NR NR NR 44 25/41 NR

45 42 33 6 23/52 23/32

20 16 18 5 10/16 11/15

37 8 21 14 12/40 32/36

28 18 28 23 17/40 18/38

NR NR NR NR 5/9 14/16

NR NR NR NR NR 76/101

247/277 (89) 160/170 (94) 136/144 (94) 235/267 (88) 481/829 (58) 535/693 (77)

29 2 25 15 2 2 5 1 6 1 0 1 3 0 NR

59 3 47 34 6 2 5 0 11 4 2 1 1 1 8

18 1 17 7 6 3 0 1 1 1 0 0 0 0 2

33 3 28 24 0 0 2 0 3 1 1 0 1 0 4

31 NR NR 19 NR NR 5 NR 5 4 NR NR NR NR 6

14 NR 12 9 3 0 1 0 1 0 0 0 1 0 0

50 24 91 37 7 20 20 4 15 3 1 0 4 0 24

868/1015 (86) 82/961 (9) 619/946 (65) 423/1015 (42) 25/946 (3) 79/946 (8) 124/1015 (12) 7/946 (0.7) 208/986 (21) 90/986 (9) 14/946 (1) 13/946 (1) 58/946 (6) 11/946 (1) 53/969 (5)

NR NR NR 36

NR 4 NR 28

3 1 4 5

1 2 1 22

NR 2 NR 17

NR 1 NR 12

2 NR NR 66

54/702 (8) 53/861 (6) 103/377 (27) 409/979 (42)

Most cases of PVO resulted from hematogenous dissemination from a remote site of infection, most commonly the urinary tract. Soft-tissue infections, distant from the site of vertebral infection, intravenous catheters, respiratory and gastrointestinal tract, or oral infection were less common sources of bacterial seeding. Paraspinal or epidural extension of the PVO is the most frequently reported complication. The cornerstone of nonsurgical treatment for uncomplicated PVO is intravenous antibiotics followed by oral

antibiotics, along with spinal immobilization. The optimal duration of therapy is unknown. Usually, antibiotics are given intravenously for 4 to 6 weeks and most patients were given further oral therapy for 2 to 6 weeks (10,12,13,21,23). However, intravenous antibiotics were given for less than 4 weeks in some patients (13,21). Oral antibiotics as the only or main therapy were given in several cases (10,13). This lack of consensus led to the recent publication of recommendations for managing PVO,

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based on descriptive studies and expert opinion (26). According to this report, intravenous antimicrobials should be given for 2 weeks if the CRP levels are back to normal at that time and for 3 weeks otherwise, at which point oral maintenance treatment should be administered. Moreover, it is suggested that the intravenous phase of treatment can be shortened or even entirely eliminated provided the organism is highly susceptible to antimicrobials and the patient has negative blood cultures, normal motor function, and no evidence of endocarditis. Given that the diagnosis of PVO is usually delayed (11-59 days), the above-mentioned authors suggested that antimicrobials should be given for at least 12 weeks, as recommended for chronic bone infection. However, the duration of antibiotic therapy should be adapted to each patient’s profile (clinical, laboratory, imaging, and immunological). Surgical intervention is reserved for specific indications such as the identification of the causative organism via an open biopsy, symptomatic spinal cord compression or radicular neurologic deficit, correction of deformity, and, finally, management of severe persistent pain. Despite the surgical advances and availability of antibiotics, there is a significant mortality and relapse following PVO. Although specified only in a few cases (10,12,14,19), infection-related mortality and relapses appeared to be associated with S. aureus sepsis. Recurrent bacteremia, chronic draining sinuses, and paravertebral abscesses were reported to be independent risk factors for relapse (13). The clinical value of follow-up imaging of PVO is questioned since imaging abnormalities were found to persist for several months (especially MRI) despite clinical and biological cure of PVO and were not associated with increased risk of relapse (15). Finally, longer time to diagnosis, hospital acquisition of the pathogen, and neurologic deficits such as motor weakness or paralysis are independent risk factors for adverse outcome in patients with PVO (13). In conclusion, PVO is primarily an illness of middle age with nonspecific symptoms and clinical findings, with relapses and sequelae. Early diagnosis is mandatory to prevent adverse outcomes. Therefore, detailed knowledge of the disease along with a high index of suspicion in patients presenting with insidious onset back pain and fever are required to avoid diagnostic delay. REFERENCES 1. Gasbarrini AL, Bertoldi E, Mazzetti M, Fini L, Terzi S, Gonella F, et al. Clinical features, diagnostic and therapeutic approaches to haematogenous vertebral osteomyelitis. Eur Rev Med Pharmacol Sci 2005;9:53-66. 2. Lehovsky J. Pyogenic vertebral osteomyelitis/disc infection. Bail Clin Rheum 1999;13(1):59-75. 3. Balériaux DL, Neugroschl C. Spinal and spinal cord infection. Eur Radiol 2004;14:E72-83.

Pyogenic vertebral osteomyelitis

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