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Hematogenous anaerobic vertebral osteomyelitis due to Bacteroides fragilis in a diabetic patient
European Journal of Internal Medicine 14 (2003) 63–64 www.elsevier.com / locate / ejim
Brief report
Hematogenous anaerobic vertebral osteomyelitis due to Bacteroides fragilis in a diabetic patient D. Boutoille*, J.P. Talarmin, V. Prendki, F. Raffi ´ ˆ , Centre Hospitalo-Universitaire de Nantes, Place Alexis Ricordeau, Service de Medecine Interne B et de Maladies Infectieuses, Hotel-Dieu Nantes Cedex 44093, France Received 21 May 2002; received in revised form 26 September 2002; accepted 8 October 2002
Abstract We report the case of a 70-year-old diabetic man with spontaneous vertebral osteomyelitis due to Bacteroides fragilis. Diagnosis was obtained on positive blood cultures. The port of entry remained unknown despite extensive investigation. A combination of metronidazole ´ and clindamycin led to a clinical cure with no need for surgical debridement and no relapse after 9 months of follow-up. 2002 Elsevier Science B.V. All rights reserved. Keywords: Osteomyelitis; Bacteroides fragilis; Metronidazole; Clindamycin
1. Introduction Anaerobic vertebral osteomyelitis is very unusual, and little information is available on the prognosis and treatment of this condition. Most of the reported cases have involved either Peptostreptococcus, Fusobacterium nucleatum, or Propionibacterium acnes and have been secondary to surgical procedures. However, spontaneous hematogenous forms are exceptional, especially those involving Bacteroides fragilis.
2. Case report A 70-year-old man was admitted for febrile (39 8C) low back pain of 4-day duration. His medical history consisted of arterial hypertension and diabetes mellitus. No invasive procedures or surgery had been performed within the previous weeks. Initial physical examination showed diffuse paravertebr*Corresponding author. Tel.: 133-2-4008-3328; fax: 133-2-40083309. E-mail address: [email protected] (D. Boutoille).
al muscular tenderness, with pain upon percussion over the spine from the third to the fifth lumbar vertebrae. Leukocyte count was 18,000 / ml; C-reactive protein was 174 mg / l. Radiographs of the spine were normal. Magnetic resonance imaging with gadolinium contrast revealed vertebral osteomyelitis involving both the third / fourth and fourth / fifth lumbar vertebral disks. Destruction was limited to the margins of the adjacent endplates and there was no paravertebral abscess or spread to the adjacent muscular structures. Three blood cultures yielded B. fragilis, which was resistant to penicillin, but susceptible to amoxicillinclavulanate, metronidazole, and clindamycin. Urine samples were sterile. Because blood cultures permitted early bacterial identification, we chose not to perform a CTguided vertebral biopsy. There were no skin lesions or foot ulcers. An abdominopelvic CT scan showed no evidence of a deep abscess, typhlitis, aortic aneurysm, or tumor. Likewise, colonoscopy, urography, and echocardiography showed no abnormalities. Dental assessment was also negative. The patient was treated with an intravenous 1.5-g daily dose of metronidazole and a 1800-mg daily dose of clindamycin for a week, followed by a 5-week oral course
0953-6205 / 02 / $ – see front matter 2002 Elsevier Science B.V. All rights reserved. doi:10.1016 / S0953-6205(02)00214-5
64
D. Boutoille et al. / European Journal of Internal Medicine 14 (2003) 63–64
of the same drug combination. Clindamycin alone was continued 4 weeks after discontinuation of metronidazole. Apyrexia was achieved within 1 week, and back pain resolved within 2 weeks. Control blood cultures were negative at day 6. C-reactive protein normalized within 3 weeks. After 3 weeks on antibiotic therapy, lumbar spine radiographs showed a narrowing of the third / fourth and fourth / fifth lumbar vertebral disks and irregularities of the margins of the vertebral endplates. After a 9-month followup, the patient was still free of disease.
3. Discussion Most reported cases of anaerobic vertebral osteomyelitis have been secondary to surgical procedures. For example, one case due to B. fragilis followed anal dilatation [1] and another was associated with a contained rupture of an aneurysm of the common iliac artery [2]. In the literature, we found no report of spontaneous vertebral osteomyelitis caused by B. fragilis. Some diseases are considered predisposing factors, such as sickle-cell disease [3,4], rheumatoid arthritis [5–7], and even Gaucher’s disease. Diabetes mellitus is a well-known predisposing condition to hematogenous osteomyelitis because of the impairment of immune defences and decreased bone vascularization. It most likely contributed to the reported case. In our patient, despite extensive investigation, no port of entry could be found. This is not exceptional in vertebral osteomyelitis because microscopic infectious sources can remain undiscovered. B. fragilis is frequently resistant to penicillin because of b-lactamase production, but it usually remains susceptible to metronidazole. Metronidazole and clindamycin are drugs of choice to treat this infection because of their excellent bone diffusion and the early oral shift permitted by their excellent bioavailability. In this case, we used both of these antibiotics for 6 weeks, despite the fact that there is no demonstrated in vitro synergy between them. Using only one antibiotic could have been sufficient, but data are lacking that might guide optimal antibiotic therapy for this disease. Moreover, a 6-week course of antibiotics is usually recommended in vertebral osteomyelitis. Chazan et al. reported a successful 8-week treatment of a case of B. fragilis vertebral osteomyelitis with metronidazole [1].
Anaerobic bacteria are difficult to isolate and depend on an adapted transport container (especially for surgical samples) and fast handling to the laboratory. In this report, bacteria grew within 24 h in blood cultures. We therefore decided not to perform more aggressive investigations such as vertebral biopsies. However, in many cases, CT-guided aspirations or surgical procedures are needed to obtain samples for microbiological diagnosis [8]. The pathogenic role of anaerobic bacteria in bone and joint infection remains underestimated because of these diagnostic difficulties. In conclusion, this report highlights an uncommon infection caused by B. fragilis and underlines the need to obtain bacteriological documentation in vertebral osteomyelitis, as unusual pathogens may be responsible, in order to provide the best antibiotic therapy. Diabetes mellitus could be a predisposing factor for anaerobic vertebral osteomyelitis. We suggest that anaerobic coverage be included in empirical antibiotic therapy of diabetic patients with ‘spontaneous’ vertebral osteomyelitis.
References [1] Chazan B, Strahilevitz J, Millgram MA, Kaufmann S, Raz R. Bacteroides fragilis vertebral osteomyelitis secondary to anal dilatation. Spine 2001;26(16):E377–8. [2] Doita M, Marui T, Kurosaka M et al. Contained rupture of the aneurysm of common iliac artery associated with pyogenic vertebral spondylitis. Spine 2001;26(13):E303–7. [3] Nehra A, Mehta RN, Encarnacion C. Bacteroides fragilis arthritis in a patient with sickle cell-disease. Am J Med 1993;94(1):21–8. [4] Kostantopoulos K, Avlami A, Demarongona K et al. Bacteroides fragilis arthritis in sickle cell-thalassemia patient. Scand J Infect Dis 1994;26(4):495–7. [5] Dodd MJ, Griffiths ID, Freeman R. Pyogenic arthritis due to Bacteroides complicating rheumatoid arthritis. Ann Rheum Dis 1982;41(3):248–9. [6] Dawes PT, Hothersall TE. Septic polyarthritis due to Bacteroides fragilis in a patient with rheumatoid arthritis. Clin Rheumatol 1984;3(3):381–3. [7] Ryeen AC, Schean A, Agell BO. A case of septic arthritis in multiple joints due to Bacteroides fragilis in a patient with rheumatoid arthritis. Acta Orthop Scand 1978;49(1):98–101. [8] Brook I. Two cases of diskitis attributable to anaerobic bacteria in children. Pediatrics 2001;107(2):E26.
Brief report
Hematogenous anaerobic vertebral osteomyelitis due to Bacteroides fragilis in a diabetic patient D. Boutoille*, J.P. Talarmin, V. Prendki, F. Raffi ´ ˆ , Centre Hospitalo-Universitaire de Nantes, Place Alexis Ricordeau, Service de Medecine Interne B et de Maladies Infectieuses, Hotel-Dieu Nantes Cedex 44093, France Received 21 May 2002; received in revised form 26 September 2002; accepted 8 October 2002
Abstract We report the case of a 70-year-old diabetic man with spontaneous vertebral osteomyelitis due to Bacteroides fragilis. Diagnosis was obtained on positive blood cultures. The port of entry remained unknown despite extensive investigation. A combination of metronidazole ´ and clindamycin led to a clinical cure with no need for surgical debridement and no relapse after 9 months of follow-up. 2002 Elsevier Science B.V. All rights reserved. Keywords: Osteomyelitis; Bacteroides fragilis; Metronidazole; Clindamycin
1. Introduction Anaerobic vertebral osteomyelitis is very unusual, and little information is available on the prognosis and treatment of this condition. Most of the reported cases have involved either Peptostreptococcus, Fusobacterium nucleatum, or Propionibacterium acnes and have been secondary to surgical procedures. However, spontaneous hematogenous forms are exceptional, especially those involving Bacteroides fragilis.
2. Case report A 70-year-old man was admitted for febrile (39 8C) low back pain of 4-day duration. His medical history consisted of arterial hypertension and diabetes mellitus. No invasive procedures or surgery had been performed within the previous weeks. Initial physical examination showed diffuse paravertebr*Corresponding author. Tel.: 133-2-4008-3328; fax: 133-2-40083309. E-mail address: [email protected] (D. Boutoille).
al muscular tenderness, with pain upon percussion over the spine from the third to the fifth lumbar vertebrae. Leukocyte count was 18,000 / ml; C-reactive protein was 174 mg / l. Radiographs of the spine were normal. Magnetic resonance imaging with gadolinium contrast revealed vertebral osteomyelitis involving both the third / fourth and fourth / fifth lumbar vertebral disks. Destruction was limited to the margins of the adjacent endplates and there was no paravertebral abscess or spread to the adjacent muscular structures. Three blood cultures yielded B. fragilis, which was resistant to penicillin, but susceptible to amoxicillinclavulanate, metronidazole, and clindamycin. Urine samples were sterile. Because blood cultures permitted early bacterial identification, we chose not to perform a CTguided vertebral biopsy. There were no skin lesions or foot ulcers. An abdominopelvic CT scan showed no evidence of a deep abscess, typhlitis, aortic aneurysm, or tumor. Likewise, colonoscopy, urography, and echocardiography showed no abnormalities. Dental assessment was also negative. The patient was treated with an intravenous 1.5-g daily dose of metronidazole and a 1800-mg daily dose of clindamycin for a week, followed by a 5-week oral course
0953-6205 / 02 / $ – see front matter 2002 Elsevier Science B.V. All rights reserved. doi:10.1016 / S0953-6205(02)00214-5
64
D. Boutoille et al. / European Journal of Internal Medicine 14 (2003) 63–64
of the same drug combination. Clindamycin alone was continued 4 weeks after discontinuation of metronidazole. Apyrexia was achieved within 1 week, and back pain resolved within 2 weeks. Control blood cultures were negative at day 6. C-reactive protein normalized within 3 weeks. After 3 weeks on antibiotic therapy, lumbar spine radiographs showed a narrowing of the third / fourth and fourth / fifth lumbar vertebral disks and irregularities of the margins of the vertebral endplates. After a 9-month followup, the patient was still free of disease.
3. Discussion Most reported cases of anaerobic vertebral osteomyelitis have been secondary to surgical procedures. For example, one case due to B. fragilis followed anal dilatation [1] and another was associated with a contained rupture of an aneurysm of the common iliac artery [2]. In the literature, we found no report of spontaneous vertebral osteomyelitis caused by B. fragilis. Some diseases are considered predisposing factors, such as sickle-cell disease [3,4], rheumatoid arthritis [5–7], and even Gaucher’s disease. Diabetes mellitus is a well-known predisposing condition to hematogenous osteomyelitis because of the impairment of immune defences and decreased bone vascularization. It most likely contributed to the reported case. In our patient, despite extensive investigation, no port of entry could be found. This is not exceptional in vertebral osteomyelitis because microscopic infectious sources can remain undiscovered. B. fragilis is frequently resistant to penicillin because of b-lactamase production, but it usually remains susceptible to metronidazole. Metronidazole and clindamycin are drugs of choice to treat this infection because of their excellent bone diffusion and the early oral shift permitted by their excellent bioavailability. In this case, we used both of these antibiotics for 6 weeks, despite the fact that there is no demonstrated in vitro synergy between them. Using only one antibiotic could have been sufficient, but data are lacking that might guide optimal antibiotic therapy for this disease. Moreover, a 6-week course of antibiotics is usually recommended in vertebral osteomyelitis. Chazan et al. reported a successful 8-week treatment of a case of B. fragilis vertebral osteomyelitis with metronidazole [1].
Anaerobic bacteria are difficult to isolate and depend on an adapted transport container (especially for surgical samples) and fast handling to the laboratory. In this report, bacteria grew within 24 h in blood cultures. We therefore decided not to perform more aggressive investigations such as vertebral biopsies. However, in many cases, CT-guided aspirations or surgical procedures are needed to obtain samples for microbiological diagnosis [8]. The pathogenic role of anaerobic bacteria in bone and joint infection remains underestimated because of these diagnostic difficulties. In conclusion, this report highlights an uncommon infection caused by B. fragilis and underlines the need to obtain bacteriological documentation in vertebral osteomyelitis, as unusual pathogens may be responsible, in order to provide the best antibiotic therapy. Diabetes mellitus could be a predisposing factor for anaerobic vertebral osteomyelitis. We suggest that anaerobic coverage be included in empirical antibiotic therapy of diabetic patients with ‘spontaneous’ vertebral osteomyelitis.
References [1] Chazan B, Strahilevitz J, Millgram MA, Kaufmann S, Raz R. Bacteroides fragilis vertebral osteomyelitis secondary to anal dilatation. Spine 2001;26(16):E377–8. [2] Doita M, Marui T, Kurosaka M et al. Contained rupture of the aneurysm of common iliac artery associated with pyogenic vertebral spondylitis. Spine 2001;26(13):E303–7. [3] Nehra A, Mehta RN, Encarnacion C. Bacteroides fragilis arthritis in a patient with sickle cell-disease. Am J Med 1993;94(1):21–8. [4] Kostantopoulos K, Avlami A, Demarongona K et al. Bacteroides fragilis arthritis in sickle cell-thalassemia patient. Scand J Infect Dis 1994;26(4):495–7. [5] Dodd MJ, Griffiths ID, Freeman R. Pyogenic arthritis due to Bacteroides complicating rheumatoid arthritis. Ann Rheum Dis 1982;41(3):248–9. [6] Dawes PT, Hothersall TE. Septic polyarthritis due to Bacteroides fragilis in a patient with rheumatoid arthritis. Clin Rheumatol 1984;3(3):381–3. [7] Ryeen AC, Schean A, Agell BO. A case of septic arthritis in multiple joints due to Bacteroides fragilis in a patient with rheumatoid arthritis. Acta Orthop Scand 1978;49(1):98–101. [8] Brook I. Two cases of diskitis attributable to anaerobic bacteria in children. Pediatrics 2001;107(2):E26.