- Email: [email protected]
Use of sulesomab in the diagnosis of brucellar spondylitis
1020 Clinical Microbiology and Infection, Volume 10 Number 11, November 2004
RESEARCH NOTE Use of sulesomab in the diagnosis of brucellar spondylitis A. Cascio1,2, C. Iaria1,2, A. Campennı`3, A. Blandino4 and S. Baldari3 1
Scuola di Specializzazione in Malattie Infettive, Dipartimento di Patologia Umana, Universita` di Messina, 2AILMI (Associazione Italiana per la Lotta contro le Malattie Infettive), 3Divisione di Medicina Nucleare, Dipartimento di Scienze Radiologiche and 4Dipartimento di Scienze Radiologiche, Universita` di Messina, Messina, Italy
ABSTRACT Twenty-two patients with suspected brucellar spondylitis were investigated to evaluate the possible diagnostic role of Sulesomab, a 99mTcantigranulocyte antibody Fab¢ fragment. Sensitivity and specificity were compared with those of magnetic resonance imaging (MRI). Skeletal involvement was detected by MRI in 11 cases, while leukoscintigraphy indicated normal vertebral uptake in seven of these patients, increased uptake in two patients, and decreased uptake in two patients. Leukoscintigraphy of the 11 patients negative by MRI demonstrated increased uptake in two cases. The sensitivity and specificity of leukoscintigraphy were 27.2% and 81.1%, respectively. Based on these results, leukoscintigraphy is not indicated for the management of patients with suspected brucellar spondylitis. Keywords Brucellosis, LeukoScan, leukoscintigraphy, spondylitis, Sulesomab Original Submission: 13 January 2004; Revised Submission: 20 February 2004; Accepted: 26 March 2004
Clin Microbiol Infect 2004; 10: 1020–1022 10.1111/j.1469-0691.2004.00961.x
Corresponding author and reprint requests: A. Cascio, AILMI (Associazione Italiana per la Lotta contro le Malattie Infettive), c ⁄ o Scuola di Specializzazione in Malattie Infettive, Universita` di Messina, Via Consolare Valeria n. 1, 98125 Messina, Italy E-mail: [email protected]
Brucellosis is an infectious zoonosis endemic to the Mediterranean basin, the Middle East, and Central and South America. Brucella spp. are facultative intracellular bacteria that can multiply within mononuclear phagocytes of the reticuloendothelial system. This fact may explain some of the clinical manifestations of systemic brucellosis, such as the propensity for involvement of the skeletal system [1,2]. Osteoarticular diseases are the most common complications and have been described in 10–85% of patients. Spondylitis is the most important localisation [3], but early diagnosis is often difficult for at least three reasons: equivocal symptoms, such as diffuse arthromyalgias (with back pain), are also found frequently in non-complicated cases of brucellosis; there is a long latent stage of up to 3 months between the onset of symptoms and the appearance of radiological changes [4]; and laboratory tests are of limited value [5]. The purpose of this prospective study was to evaluate the possible role of Sulesomab, a 99m Tc-antigranulocyte antibody Fab¢ fragment (LeukoScan; Immunomedics Inc., Morris Plains, NJ, USA) in the diagnosis of brucellar spondylitis. This radiotracer, because of its capacity to accumulate in infectious foci, has been used successfully in the diagnosis of orthopaedic infections [6–8]. The results obtained were compared with those from magnetic resonance imaging (MRI). Thirty-six consecutive patients with brucellosis were enrolled in the study, of whom 22 with suspected spondylitis were investigated with LeukoScan and MRI. Patients were considered to have brucellosis if at least two of the following criteria were present: isolation of Brucella spp. from blood or other tissue; a standard tube agglutination titre of antibodies to Brucella spp. of > 1:160; and the presence of clinical signs compatible with brucellosis (i.e., fever, sweats, arthralgias, hepatomegaly, splenomegaly and ⁄ or signs of focal disease). Spondylitis was suspected if one or more of the following signs and symptoms were present: back pain; tenderness in the paravertebral muscles; pain when pressuring or percussing the spinous processes of the vertebrae; radicular symptoms. MRI investigation was performed by spin-echo sequences with a short time repetition ⁄ time echo in the sagittal and axial planes. T1-weighted images were obtained before and after intravenous administration of gadopentate dimeglumine.
2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 10, 1006–1035
Research Note 1021
T1-weighted images with fat suppression were obtained for all patients. A diagnosis of spondylitis was confirmed by the presence of partial homogeneous hypointensity on T1-weighted images and ⁄ or hyperintensity on T2-weighted images, with or without disk or soft tissue involvement in vertebral bodies [9]. Informed consent was obtained from the patients. LeukoScan investigation was performed 4 and 24 h after administration of 555 MBq of the radiotracer (99mTc—0.25 mg monoclonal antibody; injected within a few minutes of being prepared) with a dual-headed gamma camera (Picher Odissey; Picher, Vimercate, Italy) equipped with a low-energy high-resolution collimator, photopeak 140 keV ± 20%. Planar (acquisition time 600 s) and SPET images (step and shoot, angular step 3, acquisition time 25 s, non-circular orbiter) of the regions of interest were obtained. LeukoScan images were interpreted as positive for infection when uptake in the region of interest exceeded uptake in reference points or in the presence of photopenia [10]. The sensitivity and specificity of investigation by LeukoScan were calculated by taking the results of MRI as the reference. Of the 36 patients with brucellosis, 22 (61.1%) were suspected of having spondylitis. MRI of these 22 patients detected skeletal involvement in 11 cases; other alterations detected included a paraspinal abscess
in nine patients, a psoas abscess in four patients, and epidural extension of the disease in ten patients. Involvement of the intervertebral disk was observed in ten patients. Leukoscintigraphy of the 11 patients positive by MRI demonstrated normal vertebral activity in seven cases, increased uptake in two cases (both lumbar tract), and decreased uptake in two cases (one dorsal tract and one dorsal–lumbar tract). In one of the two patients with increased antigranulocyte uptake, this did not correspond with the skeletal involvement demonstrated by MRI. Leukoscintigraphy of the 11 patients who were negative by MRI demonstrated increased uptake in two cases, while none of these patients showed decreased uptake. Considering both hyperactivity and hypoactivity, the sensitivity and specificity of LeukoScan were 27.2% (95% CI, 6–60.9) and 81.1% (95% CI, 48.2–97.7), respectively, while the negative and positive predictive values were 52% (95% CI, 27.8–77) and 60% (95% CI, 14.6–94.7), respectively. Table 1 summarises the clinical characteristics of the 36 patients enrolled in the study. The imaging examinations used most widely for the diagnosis of brucellar spondylitis are 99m Tm-methylene diphosphonate scintigraphy and MRI, but both have intrinsic methodological limits. Bone scintigraphy, although very sensitive, lacks specificity. Thus, the sensitivity and specificity for detection of osteomyelitis range from
Table 1. Characteristics of 25 patients with brucellosis but not spondylitis compared with those of 11 patients with brucellosis and spondylitis Characteristic Mean age, years (range; SD) Males Living in rural areas Occupational exposure Ingestion of unpasteurised dairy products Mean duration of symptoms before diagnosis, days (range; SD) Mean erythrocyte sedimentation rate, mm ⁄ h (range; SD) Positive blood cultures STAT median titre (range; GMT) Fever Sweats Arthromyalgias Headache Sciatica Back or neck pain Sacroilitis Peripheral arthritis Testicular pain Leukopenia (< 4000 leukocytes ⁄ mm3) Increase in serum hepatic transaminases
Patients with spondylitis (n = 11)
Patients without spondylitis (n = 25)
pa
61.8 7 3 1 11 105.2
48 10 11 4 14 37.5
0.035 NS NS NS NS 0.007
(29–75; 12.7) (63.6%) (42.8%) (9%) (100%) (15–300; 102)
(21–80; 18.7) (40%) (44%) (16%) (56%) (3–180; 41.6)
64.9 (8–124; 35.6)
49.2 (21–80; 29.7)
NS
4⁄5 800 10 3 11 2 5 11 0 1 0 1 3
7 ⁄ 15 400 25 13 18 0 1 11 1 2 1 4 12
0.09 NS NS NS 0.058 0.035 0.004 0.037 NS NS NS NS NS
(0–1600; 691) (90.9%) (27.2%) (100%) (18.1%) (45.4%) (100%) (9%) (9%) (27.2%)
(100–6400; 408) (100%) (52%) (72%) (4%) (44%) (4%) (8%) (4%) (16%) (48%)
a The t-test and Fisher’s exact test were used as appropriate. GMT, geometric mean titre; NS, not significant; STAT, standard tube agglutination testing.
2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 10, 1006–1035
1022 Clinical Microbiology and Infection, Volume 10 Number 11, November 2004
69% to 100% and 38% to 94%, respectively [11]. In contrast, although the sensitivity and specificity of MRI are very high (96% and 92%, respectively [12,13]), this diagnostic technique has the major drawbacks of high cost, lack of universal availability, imaging interference caused by metal implants, lower resolution of calcified bone structures and the cortex, and patient claustrophobia during testing [13,14]. Imaging with technetium-labelled anti-leukocyte antibodies has high sensitivity and specificity for the detection of orthopaedic infections, and is low in cost, non-invasive and rapid [6,13]. LeukoScan is used for imaging inflammation in vivo. However, it has been shown [15] that Sulesomab does not localise in inflammation, as a result of binding to circulating granulocytes, and that it is cleared into inflammation non-specifically via increased vascular permeability (it may be cleared after local binding to primed granulocytes or it can bind to activated, migrated extravascular granulocytes). In addition, image positivity in inflammation depends significantly on local blood-pool expansion [15]. When the area of interest demonstrates increased uptake relative to reference points, leukocyte images are usually interpreted as positive for infection; however, osteomyelitis presenting as an area of photopenia, especially in the spine, has been described in the literature [16–20]. For this reason, both hyperactivity and photopenia were considered as positive in the current study. However, the results obtained in this series of patients were unsatisfactory, and LeukoScan was also negative in a patient where MRI showed an evident psoas abscess. Thus, in contrast to what was hoped, LeukoScan was not useful for the investigation of patients with suspected brucellar spondylitis, and its use for this purpose is not recommended. REFERENCES 1. Young EJ. An overview of human brucellosis. Clin Infect Dis 1995; 21: 283–289. 2. Cascio A, Scarlata F, Giordano S, Antinori S, Colomba C, Titone L. Treatment of human brucellosis with rifampin plus minocycline. J Chemother 2003; 15: 248–252.
3. Solera J, Lozano E, Martinez-Alfaro E, Espinosa A, Castillejos ML, Abad L. Brucellar spondylitis: review of 35 cases and literature survey. Clin Infect Dis 1999; 29: 1440– 1449. 4. Samra Y, Hertz M, Shaked Y, Zwas S, Altman G. Brucellosis of the spine. J Bone Joint Surg Br 1982; 64: 429–431. 5. Nas K, Gur A, Kemaloglu MS et al. Management of spinal brucellosis and outcome of rehabilitation. Spinal Cord 2001; 39: 223–227. 6. Hakki S, Harwood SJ, Morissey MA, Camblin JG, Laven DL, Webster WB. Comparative study of monoclonal antibody scan in diagnosing orthopaedic infection. Clin Orthop 1997; 335: 275–285. 7. Becker W, Palestro CJ, Winship J et al. Rapid imaging of infections with a monoclonal antibody fragment (Leukoscan). Clin Orthop 1996; 329: 263–272. 8. Harwood SJ, Valdivia S, Hung GL, Quenzer RW. Use of Sulesomab, a radiolabeled antibody fragment, to detect osteomyelitis in diabetic patients with foot ulcers by leukoscintigraphy. Clin Infect Dis 1999; 28: 1200–1205. 9. Ozaksoy D, Yucesoy K, Yucesoy M, Kovanlikaya I, Yuce A, Naderi S. Brucellar spondylitis: MRI findings. Eur Spine J 2001; 10: 529–533. 10. Palestro CJ, Kim CK, Swyer AJ, Vallabhajosula S, Goldsmith SJ. Radionuclide diagnosis of vertebral osteomyelitis: indium-111-leukocyte and technetium-99m-methylene diphosphonate bone scintigraphy. J Nucl Med 1991; 32: 1861–1865. 11. Yang DC, Ratani RS, Mittal PK, Chua RS, Pate SM. Radionuclide three-phase whole-body bone imaging. Clin Nucl Med 2002; 27: 419–426. 12. Modic MT, Feiglin DH, Piraino DW et al. Vertebral osteomyelitis: assessment using MR. Radiology 1985; 157: 157–166. 13. Shirtliff ME, Mader JT. Imaging in osteomyelitis and septic arthritis. Curr Treat Options Infect Dis 2003; 5: 323–335. 14. Erdman WA, Tamburro F, Jayson HT, Weatherall PT, Ferry KB, Peshock RM. Osteomyelitis: characteristics and pitfalls of diagnosis with MR imaging. Radiology 1991; 180: 533–539. 15. Skehan SJ, White JF, Evans JW et al. Mechanism of accumulation of 99mTc-sulesomab in inflammation. J Nucl Med 2003; 44: 11–18. 16. Brown ML, Hauser MF, Aznarez A, Fitzerald RH. Indium111-leukocyte imaging: the skeletal photopenic lesions. Clin Nucl Med 1985; 11: 611–613. 17. Datz FL. Thorne DA. Cause and significance of cold bone defects on indium-111-labeled leukocyte imaging. J Nucl Med 1987; 28: 820–823. 18. Wukich DK, Van Dam B, Abreu SH. Preoperative indiumlabeled white blood cells scintigraphy in suspected osteomyelitis of the axial skeleton. Spine 1988; 13: 1168–1170. 19. Whalen JL, Brown ML, McCleod R, Fitzgerald RH. Limitations of indium-leukocyte imaging for the diagnosis of spine infections. Spine 1991; 16: 193–197. 20. Eisenberg B, Power JE, Alavi A. Cold defects in In-111 labeled leukocyte imaging of osteomyelitis in the axial skeleton. Clin Nucl Med 1991; 16: 103–106.
2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 10, 1006–1035
RESEARCH NOTE Use of sulesomab in the diagnosis of brucellar spondylitis A. Cascio1,2, C. Iaria1,2, A. Campennı`3, A. Blandino4 and S. Baldari3 1
Scuola di Specializzazione in Malattie Infettive, Dipartimento di Patologia Umana, Universita` di Messina, 2AILMI (Associazione Italiana per la Lotta contro le Malattie Infettive), 3Divisione di Medicina Nucleare, Dipartimento di Scienze Radiologiche and 4Dipartimento di Scienze Radiologiche, Universita` di Messina, Messina, Italy
ABSTRACT Twenty-two patients with suspected brucellar spondylitis were investigated to evaluate the possible diagnostic role of Sulesomab, a 99mTcantigranulocyte antibody Fab¢ fragment. Sensitivity and specificity were compared with those of magnetic resonance imaging (MRI). Skeletal involvement was detected by MRI in 11 cases, while leukoscintigraphy indicated normal vertebral uptake in seven of these patients, increased uptake in two patients, and decreased uptake in two patients. Leukoscintigraphy of the 11 patients negative by MRI demonstrated increased uptake in two cases. The sensitivity and specificity of leukoscintigraphy were 27.2% and 81.1%, respectively. Based on these results, leukoscintigraphy is not indicated for the management of patients with suspected brucellar spondylitis. Keywords Brucellosis, LeukoScan, leukoscintigraphy, spondylitis, Sulesomab Original Submission: 13 January 2004; Revised Submission: 20 February 2004; Accepted: 26 March 2004
Clin Microbiol Infect 2004; 10: 1020–1022 10.1111/j.1469-0691.2004.00961.x
Corresponding author and reprint requests: A. Cascio, AILMI (Associazione Italiana per la Lotta contro le Malattie Infettive), c ⁄ o Scuola di Specializzazione in Malattie Infettive, Universita` di Messina, Via Consolare Valeria n. 1, 98125 Messina, Italy E-mail: [email protected]
Brucellosis is an infectious zoonosis endemic to the Mediterranean basin, the Middle East, and Central and South America. Brucella spp. are facultative intracellular bacteria that can multiply within mononuclear phagocytes of the reticuloendothelial system. This fact may explain some of the clinical manifestations of systemic brucellosis, such as the propensity for involvement of the skeletal system [1,2]. Osteoarticular diseases are the most common complications and have been described in 10–85% of patients. Spondylitis is the most important localisation [3], but early diagnosis is often difficult for at least three reasons: equivocal symptoms, such as diffuse arthromyalgias (with back pain), are also found frequently in non-complicated cases of brucellosis; there is a long latent stage of up to 3 months between the onset of symptoms and the appearance of radiological changes [4]; and laboratory tests are of limited value [5]. The purpose of this prospective study was to evaluate the possible role of Sulesomab, a 99m Tc-antigranulocyte antibody Fab¢ fragment (LeukoScan; Immunomedics Inc., Morris Plains, NJ, USA) in the diagnosis of brucellar spondylitis. This radiotracer, because of its capacity to accumulate in infectious foci, has been used successfully in the diagnosis of orthopaedic infections [6–8]. The results obtained were compared with those from magnetic resonance imaging (MRI). Thirty-six consecutive patients with brucellosis were enrolled in the study, of whom 22 with suspected spondylitis were investigated with LeukoScan and MRI. Patients were considered to have brucellosis if at least two of the following criteria were present: isolation of Brucella spp. from blood or other tissue; a standard tube agglutination titre of antibodies to Brucella spp. of > 1:160; and the presence of clinical signs compatible with brucellosis (i.e., fever, sweats, arthralgias, hepatomegaly, splenomegaly and ⁄ or signs of focal disease). Spondylitis was suspected if one or more of the following signs and symptoms were present: back pain; tenderness in the paravertebral muscles; pain when pressuring or percussing the spinous processes of the vertebrae; radicular symptoms. MRI investigation was performed by spin-echo sequences with a short time repetition ⁄ time echo in the sagittal and axial planes. T1-weighted images were obtained before and after intravenous administration of gadopentate dimeglumine.
2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 10, 1006–1035
Research Note 1021
T1-weighted images with fat suppression were obtained for all patients. A diagnosis of spondylitis was confirmed by the presence of partial homogeneous hypointensity on T1-weighted images and ⁄ or hyperintensity on T2-weighted images, with or without disk or soft tissue involvement in vertebral bodies [9]. Informed consent was obtained from the patients. LeukoScan investigation was performed 4 and 24 h after administration of 555 MBq of the radiotracer (99mTc—0.25 mg monoclonal antibody; injected within a few minutes of being prepared) with a dual-headed gamma camera (Picher Odissey; Picher, Vimercate, Italy) equipped with a low-energy high-resolution collimator, photopeak 140 keV ± 20%. Planar (acquisition time 600 s) and SPET images (step and shoot, angular step 3, acquisition time 25 s, non-circular orbiter) of the regions of interest were obtained. LeukoScan images were interpreted as positive for infection when uptake in the region of interest exceeded uptake in reference points or in the presence of photopenia [10]. The sensitivity and specificity of investigation by LeukoScan were calculated by taking the results of MRI as the reference. Of the 36 patients with brucellosis, 22 (61.1%) were suspected of having spondylitis. MRI of these 22 patients detected skeletal involvement in 11 cases; other alterations detected included a paraspinal abscess
in nine patients, a psoas abscess in four patients, and epidural extension of the disease in ten patients. Involvement of the intervertebral disk was observed in ten patients. Leukoscintigraphy of the 11 patients positive by MRI demonstrated normal vertebral activity in seven cases, increased uptake in two cases (both lumbar tract), and decreased uptake in two cases (one dorsal tract and one dorsal–lumbar tract). In one of the two patients with increased antigranulocyte uptake, this did not correspond with the skeletal involvement demonstrated by MRI. Leukoscintigraphy of the 11 patients who were negative by MRI demonstrated increased uptake in two cases, while none of these patients showed decreased uptake. Considering both hyperactivity and hypoactivity, the sensitivity and specificity of LeukoScan were 27.2% (95% CI, 6–60.9) and 81.1% (95% CI, 48.2–97.7), respectively, while the negative and positive predictive values were 52% (95% CI, 27.8–77) and 60% (95% CI, 14.6–94.7), respectively. Table 1 summarises the clinical characteristics of the 36 patients enrolled in the study. The imaging examinations used most widely for the diagnosis of brucellar spondylitis are 99m Tm-methylene diphosphonate scintigraphy and MRI, but both have intrinsic methodological limits. Bone scintigraphy, although very sensitive, lacks specificity. Thus, the sensitivity and specificity for detection of osteomyelitis range from
Table 1. Characteristics of 25 patients with brucellosis but not spondylitis compared with those of 11 patients with brucellosis and spondylitis Characteristic Mean age, years (range; SD) Males Living in rural areas Occupational exposure Ingestion of unpasteurised dairy products Mean duration of symptoms before diagnosis, days (range; SD) Mean erythrocyte sedimentation rate, mm ⁄ h (range; SD) Positive blood cultures STAT median titre (range; GMT) Fever Sweats Arthromyalgias Headache Sciatica Back or neck pain Sacroilitis Peripheral arthritis Testicular pain Leukopenia (< 4000 leukocytes ⁄ mm3) Increase in serum hepatic transaminases
Patients with spondylitis (n = 11)
Patients without spondylitis (n = 25)
pa
61.8 7 3 1 11 105.2
48 10 11 4 14 37.5
0.035 NS NS NS NS 0.007
(29–75; 12.7) (63.6%) (42.8%) (9%) (100%) (15–300; 102)
(21–80; 18.7) (40%) (44%) (16%) (56%) (3–180; 41.6)
64.9 (8–124; 35.6)
49.2 (21–80; 29.7)
NS
4⁄5 800 10 3 11 2 5 11 0 1 0 1 3
7 ⁄ 15 400 25 13 18 0 1 11 1 2 1 4 12
0.09 NS NS NS 0.058 0.035 0.004 0.037 NS NS NS NS NS
(0–1600; 691) (90.9%) (27.2%) (100%) (18.1%) (45.4%) (100%) (9%) (9%) (27.2%)
(100–6400; 408) (100%) (52%) (72%) (4%) (44%) (4%) (8%) (4%) (16%) (48%)
a The t-test and Fisher’s exact test were used as appropriate. GMT, geometric mean titre; NS, not significant; STAT, standard tube agglutination testing.
2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 10, 1006–1035
1022 Clinical Microbiology and Infection, Volume 10 Number 11, November 2004
69% to 100% and 38% to 94%, respectively [11]. In contrast, although the sensitivity and specificity of MRI are very high (96% and 92%, respectively [12,13]), this diagnostic technique has the major drawbacks of high cost, lack of universal availability, imaging interference caused by metal implants, lower resolution of calcified bone structures and the cortex, and patient claustrophobia during testing [13,14]. Imaging with technetium-labelled anti-leukocyte antibodies has high sensitivity and specificity for the detection of orthopaedic infections, and is low in cost, non-invasive and rapid [6,13]. LeukoScan is used for imaging inflammation in vivo. However, it has been shown [15] that Sulesomab does not localise in inflammation, as a result of binding to circulating granulocytes, and that it is cleared into inflammation non-specifically via increased vascular permeability (it may be cleared after local binding to primed granulocytes or it can bind to activated, migrated extravascular granulocytes). In addition, image positivity in inflammation depends significantly on local blood-pool expansion [15]. When the area of interest demonstrates increased uptake relative to reference points, leukocyte images are usually interpreted as positive for infection; however, osteomyelitis presenting as an area of photopenia, especially in the spine, has been described in the literature [16–20]. For this reason, both hyperactivity and photopenia were considered as positive in the current study. However, the results obtained in this series of patients were unsatisfactory, and LeukoScan was also negative in a patient where MRI showed an evident psoas abscess. Thus, in contrast to what was hoped, LeukoScan was not useful for the investigation of patients with suspected brucellar spondylitis, and its use for this purpose is not recommended. REFERENCES 1. Young EJ. An overview of human brucellosis. Clin Infect Dis 1995; 21: 283–289. 2. Cascio A, Scarlata F, Giordano S, Antinori S, Colomba C, Titone L. Treatment of human brucellosis with rifampin plus minocycline. J Chemother 2003; 15: 248–252.
3. Solera J, Lozano E, Martinez-Alfaro E, Espinosa A, Castillejos ML, Abad L. Brucellar spondylitis: review of 35 cases and literature survey. Clin Infect Dis 1999; 29: 1440– 1449. 4. Samra Y, Hertz M, Shaked Y, Zwas S, Altman G. Brucellosis of the spine. J Bone Joint Surg Br 1982; 64: 429–431. 5. Nas K, Gur A, Kemaloglu MS et al. Management of spinal brucellosis and outcome of rehabilitation. Spinal Cord 2001; 39: 223–227. 6. Hakki S, Harwood SJ, Morissey MA, Camblin JG, Laven DL, Webster WB. Comparative study of monoclonal antibody scan in diagnosing orthopaedic infection. Clin Orthop 1997; 335: 275–285. 7. Becker W, Palestro CJ, Winship J et al. Rapid imaging of infections with a monoclonal antibody fragment (Leukoscan). Clin Orthop 1996; 329: 263–272. 8. Harwood SJ, Valdivia S, Hung GL, Quenzer RW. Use of Sulesomab, a radiolabeled antibody fragment, to detect osteomyelitis in diabetic patients with foot ulcers by leukoscintigraphy. Clin Infect Dis 1999; 28: 1200–1205. 9. Ozaksoy D, Yucesoy K, Yucesoy M, Kovanlikaya I, Yuce A, Naderi S. Brucellar spondylitis: MRI findings. Eur Spine J 2001; 10: 529–533. 10. Palestro CJ, Kim CK, Swyer AJ, Vallabhajosula S, Goldsmith SJ. Radionuclide diagnosis of vertebral osteomyelitis: indium-111-leukocyte and technetium-99m-methylene diphosphonate bone scintigraphy. J Nucl Med 1991; 32: 1861–1865. 11. Yang DC, Ratani RS, Mittal PK, Chua RS, Pate SM. Radionuclide three-phase whole-body bone imaging. Clin Nucl Med 2002; 27: 419–426. 12. Modic MT, Feiglin DH, Piraino DW et al. Vertebral osteomyelitis: assessment using MR. Radiology 1985; 157: 157–166. 13. Shirtliff ME, Mader JT. Imaging in osteomyelitis and septic arthritis. Curr Treat Options Infect Dis 2003; 5: 323–335. 14. Erdman WA, Tamburro F, Jayson HT, Weatherall PT, Ferry KB, Peshock RM. Osteomyelitis: characteristics and pitfalls of diagnosis with MR imaging. Radiology 1991; 180: 533–539. 15. Skehan SJ, White JF, Evans JW et al. Mechanism of accumulation of 99mTc-sulesomab in inflammation. J Nucl Med 2003; 44: 11–18. 16. Brown ML, Hauser MF, Aznarez A, Fitzerald RH. Indium111-leukocyte imaging: the skeletal photopenic lesions. Clin Nucl Med 1985; 11: 611–613. 17. Datz FL. Thorne DA. Cause and significance of cold bone defects on indium-111-labeled leukocyte imaging. J Nucl Med 1987; 28: 820–823. 18. Wukich DK, Van Dam B, Abreu SH. Preoperative indiumlabeled white blood cells scintigraphy in suspected osteomyelitis of the axial skeleton. Spine 1988; 13: 1168–1170. 19. Whalen JL, Brown ML, McCleod R, Fitzgerald RH. Limitations of indium-leukocyte imaging for the diagnosis of spine infections. Spine 1991; 16: 193–197. 20. Eisenberg B, Power JE, Alavi A. Cold defects in In-111 labeled leukocyte imaging of osteomyelitis in the axial skeleton. Clin Nucl Med 1991; 16: 103–106.
2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 10, 1006–1035