EDITORIAL
10.1111/j.1469-0691.2004.00949.x
Vertebral osteomyelitis caused by non-tuberculous mycobacteria G. Petitjean1, U. Fluckiger1, S. Scha¨ren2 and G. Laifer1 Division of Infectious Diseases and 2Department of Orthopaedic Surgery, University Hospitals Basel, Basel, Switzerland
1
ABSTRACT Vertebral osteomyelitis caused by non-tuberculous mycobacteria is a rare disease, with only 31 cases and one nosocomial outbreak reported in the literature (MedLine review between 1965 and December 2003). The clinical features are often indistinguishable from those of pyogenic osteomyelitis. Early diagnosis of such infections is a major challenge because of the slow growth of these microorganisms. No consensus guidelines for the treatment of these infections exist. Prolonged anti-mycobacterial therapy in combination with surgical debridement is recommended. Keywords
Mycobacteria, osteomyelitis, vertebral osteomyelitis
Clin Microbiol Infect 2004; 10: 951–953
Non-tuberculous mycobacteria (NTM) comprise a group of > 50 different species. They are found ubiquitously, but with marked geographical variation, in water, soil and animals (including birds). Direct transmission from animals is not important in human infections [1], and human-to-human transmission appears to be rare. Studies in the USA between 1980 and 1992 indicate that isolates of NTM have become more prevalent in recent years [2]. However, an increase in associated diseases has not been shown in immunocompetent patients. Six major clinical syndromes caused by NTM can be differentiated, of which the most important is pulmonary infection, presenting either as cavitary disease or as nodular infiltrates. Other syndromes include: local non-tender lymphadenitis; skin and soft tissue infections, with reported water-associated nosocomial outbreaks [3]; disseminated infection (> 95% associated with the Mycobacterium avium complex) in AIDS patients; and, rarely, catheter-related infections. Finally, chronic granulomatous infections of bursae, joints, tendon sheaths and bones are seen after direct inoculation of NTM through accidental trauma, surgical incisions, puncture wounds or injections.
Corresponding author and reprint requests: G. Laifer, Division of Infectious Diseases, University Hospitals Basel, Petersgraben 4, CH-4031 Basel, Switzerland E-mail:
[email protected]
Vertebral osteomyelitis (VO) caused by NTM is a very rare disease. A MedLine review of the literature between 1965 and December 2003 revealed only 31 case reports and one nosocomial outbreak [4–14]. The NTM species identified most frequently was M. avium complex (n = 13); this was followed by Mycobacterium xenopi (n = 7), Mycobacterium fortuitum (n = 5), and Mycobacterium abscessus (n = 3); there were also single cases involving Mycobacterium kansasii, Mycobacterium simiae and one unidentified non-tuberculous mycobacterium. The mean age of patients was 43 years (range 16–79 years), and there were 19 females and 13 males. Thoracic (n = 15) and lumbar spine (n = 11) were the most frequent sites of involvement; four cases with multifocal and three with thoracolumbar involvement were reported. Unlike other bone and joint infections caused by NTM, it is unusual for VO to result from direct inoculation following penetrating trauma, surgical incision or injections. A genetic defect of the interferon-c receptor with decreased in-vitro responsiveness of macrophages to interferon-c was described in three patients with multifocal osteomyelitis [9]. A recent hypothesis postulated a ‘locus minoris resistentiae’ after non-penetrating trauma as a risk factor [6]. Macrophages containing NTM could migrate to the region of a recent trauma, release mycobacteria and initiate a new focus of infection. A similar pathogenesis has been reported for tuberculous spondylitis [15].
Ó 2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases
952 Clinical Microbiology and Infection, Volume 10 Number 11, November 2004
An environmental reservoir, especially water, is the most likely source of infection, either via inhalation of contaminated aerosols (e.g., whirlpools) or by invasion through the gastrointestinal tract [16,17]. Strains of the M. avium complex with plasmids, possibly associated with virulence, have been shown to be aerosolised preferentially [18]. A nosocomial outbreak of M. xenopi spinal infections affecting > 50 patients after discovertebral surgery occurred in the 1990s in France [14]. However, positive identification of M. xenopi must be interpreted in the clinical context, because contamination with associated pseudo-outbreaks has been reported [19]. With the exception of Mycobacterium chelonae and Mycobacterium haemophilum, which may involve bones and joints, as well as being found in nodular skin lesions and bacteraemia in AIDS patients, most patients with disease of bones, joints and tendon sheaths caused by NTM do not have underlying immunosuppression. In contrast, various degrees of immunosuppression (systemic lupus erythematosus with steroids, n = 7; HIV infection, n = 4; interferon receptor defect, n = 3; carcinoma, n = 1; renal failure, n = 1; and chronic granulomatous disease, n = 1) were found in 17 (51.5%) of 33 patients with VO caused by NTM. This difference might be explained by the different mode of acquisition of NTM in VO (haematogenic, lymphogenic) compared to other skeletal infections associated with these microorganisms (direct inoculation). Two immunocompetent patients with VO caused by NTM were treated recently at our institution. The first patient, a man aged 47 years from Pakistan with a 3-month history of progressive lumbar back pain, had L1–L3 spondylodiscitis with paravertebral abscesses. Percutaneous transpedicular bone biopsy revealed necrosis without granulomas or bacteria, or acid-fast bacilli in the direct smear. Open surgery, with anterior debridement of the abscesses and bone grafting with posterior transpedicular fixation, revealed granulomas with multinuclear histiocytic giant cells and necrosis. Culture of the biopsies for 5–9 weeks yielded M. xenopi. The second patient, a woman aged 56 years with a 6-month history of progressive lumbar back pain and slow onset of pleuritic chest pain, had pleural empyema of the right hemithorax and an osteolytic lesion at T8 on computed tomography scan. Open biopsy revealed necrosis and non-specific granulation tissue with
multinuclear histiocytic giant cells. T8 open laminectomy and debridement showed caseous necrosis. After 3 weeks, mycobacterial cultures yielded an isolate of the M. avium complex from multiple biopsies. The times from first symptoms to diagnosis for these patients were 16 and 22 weeks, respectively. Treatment with a clarithromycin-containing regimen, combined with surgical debridement, resulted in a favourable outcome for both patients during the initial follow-up period of 12 months after therapy. For patients infected with slow-growing bacteria such as NTM, early diagnosis is a major challenge. Multiple cultures of bone biopsy specimens are required. Blood cultures are usually negative, as is also true for other infections caused by NTM in immunocompetent patients. Even with pyogenic VO, only 28% of episodes are diagnosed within the first month following the onset of symptoms, and diagnostic delay in these patients is an independent risk factor for an unfavourable outcome [20]. VO may have serious consequences. In pyogenic VO (only one reported patient with NTM), residual disability occurred in more than one-third of the survivors, and relapse occurred in 14% [20]. Corresponding data for VO caused by NTM are not available. No consensus guidelines concerning the treatment of spinal infections caused by NTM exist. In general, NTM are more resistant to anti-tuberculous drugs, and resistance testing in vitro is not effective in predicting the clinical response. Prolonged therapy in combination with surgical debridement is recommended strongly for all cases of VO caused by NTM, especially in patients with abscess formation. REFERENCES 1. Meissner G, Anz W. Sources of Mycobacterium aviumcomplex infection resulting in human disease. Am Rev Resp Dis 1977; 116: 1057–1064. 2. Ostroff S, Hutwagner L, Collin S. Mycobacterial species and drug resistance pattern reported by state laboratories 1992 [abstract U9]. In: Program and abstracts of the 93rd General Meeting of the American Society for Microbiology, Atlanta, GA. Washington DC: American Society for Microbiology, 1993; 170. 3. Winthrop KL, Abrams M, Yarkus M. An outbreak of mycobacterial furunculosis associated with footbaths at a nail salon. N Engl J Med 2002; 346: 1366–1371. 4. Sarria JC, Chutkan NB, Figueroa JE, Hull A. Atypical mycobacterial vertebral osteomyelitis: case report and review. Clin Infect Dis 1998; 26: 503–505.
Ó 2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 10, 951–953
Petitjean et al. Non-tuberculous mycobacterial osteomyelitis 953
5. Igram CM, Petrie SG, Harris MB. Atypical mycobacterial vertebral osteomyelitis in an immunocompetent patient. Orthopedics 1997; 20: 163–166. 6. Chan ED, Kong PM, Fennelly K, Dwyer AP, Iseman MD. Vertebral osteomyelitis due to infection with nontuberculous mycobacterium species after blunt trauma to the back: 3 examples of the principle of locus minoris resistentiae. Clin Infect Dis 2001; 32: 1506–1510. 7. Danesh-Clough T, Theis JC, Van der Linden A. Mycobacterium xenopi infection of the spine: a case report and literature review. Spine 2000; 25: 626–632. 8. Erand P, Robert-Grandpierre F, Kaeser P. Vertebral osteomyelitis caused by Mycobacterium avium–intracellulare in a patient with AIDS. Clin Microbiol Infect 1999; 5: 643– 644. 9. Arend SM, Janssen R, Gosen JJ et al. Multifocal osteomyelitis caused by nontuberculous mycobacteria in patients with a genetic defect of the interferon-c receptor. Neth J Med 2001; 59: 140–151. 10. Aberg JA, Chin-Hong PV, McCutchan A, Koletar SL, Currier JS. Localized osteomyelitis due to Mycobacterium avium complex in patients with human immunodeficiency virus receiving high active antiretroviral therapy. Clin Infect Dis 2002; 35: e8–e13. 11. Otaki Y, Nakanishi T, Nanami M. A rare combination of sites of involvement by Mycobacterium intracellulare in a hemodialysis patient: multifocal synovitis, spondylitis, and multiple skin lesions. Nephron 2002; 92: 730–734. 12. Telgt DS, Van den Hoogen FH, Meis JF, Lemmens JA, Van den Putte LB. Arthritis and spondylodiscitis caused by
13.
14.
15.
16.
17. 18.
19.
20.
Mycobacterium xenopi in a patient with systemic lupus erythematosus. Br J Rheumatol 1997; 36: 1025–1026. Kulasegaram R, Richardson D, Macrae B, de Ruiter A. Mycobacterium xenopi osteomyelitis in a patient on highly active antiretroviral therapy (HAART). Int J STD AIDS 2001; 12: 404–406. Astagneau P, Desplaces N, Vincent V et al. Mycobacterium xenopi spinal infections after discovertebral surgery: investigation and screening of a large outbreak. Lancet 2001; 358: 747–751. Weir WR, Muraleedharan MV. Tuberculosis arising at the site of physical injury: eight case histories. J Infect 1983; 7: 63–66. Collins CH, Yates MD. Infection and colonisation by Mycobacterium kansasii and Mycobacterium xenopi: aerosols as a possible source? J Infect 1984; 8: 178–179. Falkinham JO. Epidemiology of infection by nontuberculous mycobacteria. Clin Microbiol Rev 1996; 9: 177–215. Meissner PS, Falkinham JO. Plasmid DNA profiles as epidemiologic markers for clinical and environmental isolates of Mycobacterium avium, Mycobacterium intracellulare and Mycobacterium scrofulaceum. J Infect Dis 1986; 153: 325–331. Sniadack DH, Ostroff SM, Karlix MA et al. A nosocomial pseudo-outbreak of Mycobacterium xenopi due to a contaminated potable water supply: lessons in prevention. Infect Control Hosp Epidemiol 1993; 14: 636–641. McHenry MC, Easley KA, Locker G. Vertebral ostemyelitis: long-term outcome for 253 patients from seven Cleveland-area hospitals. Clin Infect Dis 2002; 34: 1342–1350.
Ó 2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 10, 951–953
