Le Infezioni in Medicina, n. 2, 95-99, 2003 Casi clinici flavescens vertebral osteomyelitis Case report in an immunocompetent host Osteomielite vertebrale da Mycobacterium flavescens in un ospite immunocompetente

Antonio Mastroianni Unità Operativa Malattie Infettive, Ospedale “G.B. Morgagni”, Forlì

■ INTRODUCTION upper lobe, and a CTscan of the thorax showed a small pleural-based lesion of 1-cm in diame- ycobacterium flavescens is an unusual ter. Bronchoscopy with bronchoalveolar lavage pathogen that, to our knowledge, has (BAL) and repeated CT-guided biopsies were Mnot been previously reported as a cause non-diagnostic. Abdominal ultrasonography of vertebral osteomyelitis. We wish to report a revealed no hepatosplenic lesion. Radiograph rare case of vertebral osteomyelitis caused by of the spine disclosed sclerosis and wedge- Mycobacterium flavescens in a subject with ap- shaped deformities of TH 10, TH 11 and TH 12. parent normal immune function, with a brief MRI showed massive spondylodiscitis of review of previous reports of human infection TH10/12, with paraspinal and intraspinal ab- caused by this atypical mycobacterium. This scess formation. Neurologic symptoms were case demonstrates that non-tuberculous my- absent. A purified protein derivative skin test cobacteria (NTM) vertebral ostemyelitis can oc- was negative. A bone debridement and a diag- cur not only in immunosuppressed patients but nostic bone biopsy were performed. Gram also in immunocompetent patients. staining of the purulent material from the ver- We have also reviewed the literature on vertebral tebral lesion showed no microorganims, while disease due to rapidly growing mycobacteria. acid fast stain revealed acid-fast . Ther- apy with isoniazid, rifampin, and streptomycin was initiated for suspected vertebral tubercu- ■ CASE REPORT lous osteomyelitis (Pott’s disease). After two consecutive months of treatment, the patient A 70-year-old man with a history of severe continued to experience low fever, lumbar pain, chronic ischemic cardiopathy and diabetes mel- night sweats, and fatigue. Mycobacterial blood litus was admitted to our hospital because of a and bone cultures drawn on admission proved 3-month history of fever, night sweats, fatigue, positive for Mycobacterium flavescens. This or- weight loss, and an increasing lower back pain ganism was susceptible to streptomycin and ri- and left-sided chest pain. On admission his fampin, and it was resistant to ethambutol and body temperature was 38 °C. Examination of isoniazid. Therapy was changed to rifampin, the joints revealed moderate signs of inflamma- ciprofloxacin and ethambutol, and the patient tory activity in the thoracic spine that was ten- improved rapidly. der to palpation. Results of laboratory tests in- Therapy was well tolerated for 13 months and cluded a leukocyte count of 89 x 109/l with neu- he completely recovered. trophils 69% and lymphocytes 32%, C-reactive protein and albumin of 120 mg/l and 28 g/l, re- spectively, and an ESR of 35 mm/h. Screening ■ DISCUSSION for HIV, syphilis and Brucella were negative. Lymphocytes subset analysis was normal. A Mycobacterial diseases cause substantial mor- chest radiograph showed an infiltrate in the left bidity and mortality throughout the world, and

97 2003 in recent years diseases caused by emergence of The diagnosis of infection due to rapidly grow- rapidly growing mycobacteria have been re- ing mycobacteria requires appropriate tissue ported from both developing and industrial- specimens to be obtained. Among the rapidly ized countries. Although most diseases due to growing mycobacteria found in abundance in pathogenic mycobacteria are caused by My- the environment, strains associated with hu- cobacterium tuberculosis, the rates of infections man disease are more frequently restricted to caused by NTM are increasingly reported in , both healthy and immunocompromised pa- and [1-3]. In addition, tients in the last decades. there are several saprophytic species of rapid NTM are ubiquitous organisms in our environ- growers documented as occasional etiological ment, ranging from harmless inhabitants of agents of disease, including Mycobacterium aquatic reservoirs and soil to species patho- phlei, , Mycobacterium genic to man and animals; in addition, NTM neoaurum, Mycobacterium flavescens, Mycobac- may also contaminate microbiological speci- terium vaccae, and the thermophilic species My- mens [1]. In recent years it has come to be ap- cobacterium thermoresistibile [1-3]. preciated that nosocomial transmission of these Extrapulmonary disease caused by NTM has a organisms is increasing [1]. broad spectrum of clinical manifestations refer- More than 65 different species have been recog- able to almost any organ system, although the nized, but many of the NTM are isolated as lab- spine is rarely affected. NTM infections of the oratory contaminants or colonizers, and infre- bones may occur following surgical proce- quently as true pathogens. Indeed, only a hand- dures, trauma, penetrating injuries or following ful of NMT are usually associated with diseases the injection of steroids. in clinical practice in humans. NTM osteomyelitis may be a complication of It has been reported that among the most com- skin and soft tissue infections most frequently mon risk factors associated with disease due to associated with a history of penetrating injury NTM are smoking, chronic lung disease, HIV or surgery. Moreover, extrapulmonary tubercu- infection, alcoholism, and less often immuno- losis due to NTM with involvement of the spine suppressive therapy, malignancy, connective remains an uncommon entity. The rarity of this tissue disease, previous Mycobacterium tubercu- condition was emphasized in recent articles [4, losis infection, , and diabetes [1-3]. 5]. NTM have been categorized into different Through an extensive literature search by groups based on characteristic colony morphol- means of MEDLINE consultation, we have ogy, growth rate, and pigmentation; growth identified only 20 cases of atypical mycobacte- rates have remained a practical means for ria vertebral osteomyelitis reported in the cur- grouping species within the laboratory [1-3]. rent English literature from 1955 to 2001 [4-7]. The rapidly growing mycobacteria include The study population consisted of 10 men and eight taxonomic groups of non-pigmented and 10 women with a mean age of 47 years (range pigmented organisms, also known as Runyon 16-79). group IV; these organisms exhibit growth in < 7 Of these cases, 5 were due to Mycobacterium days under optimal conditions in agar plates. xenopi, 4 were due to Mycobacterium avium-in- The most common disease associated with tracellulare, 4 were due to Mycobacterium fortui- these organisms is cutaneous disease associated tum, 3 were due to Mycobacterium abscessus, and with a penetrating wound or foreign body, but the remaining episodes were due to Mycobac- nosocomial infections can also occur [1-3]. terium simiae, Mycobacterium kansasii, Mycobac- Rapidly growing mycobacteria may also be as- terium bovis BCG and an atypical, non-classi- sociated with respiratory tract colonization or fied, mycobacterium. infection and surgical infections, while they are Vertebral infection caused by NTM involves the only occasionally associated with infections re- anterior inferior portion of the vertebral body, lated to hemodialysis, peritonitis in patients un- is adjacent to an intervertebral disk, and dergoing peritoneal dialysis, injection-associ- spreads under the anterior longitudinal liga- ated cutaneous and joint infections, and in- ment to involve the adjacent vertebrae, as de- travascular catheter infections [1-3]. These scribed for vertebral osteomyelitis due to My- pathogens are rarely transmitted by human-to- cobacterium tuberculosis. human contact and are resistant to common an- The most common clinical predisposing events tituberculosis drugs. preceding the diagnosis of vertebral os-

98 2003 teomyelitis included systemic lupus erythema- with chronic granulomatous disease [8-10]. tous and steroid therapy in four patients, and This was the first report of Mycobacterium back injury in 4 other patients. Other underly- flavescens disseminated infection. ing conditions included intravenous drug Mycobacterium flavescens was also cultured from abuse, HIV disease, hypertension, breast cancer the CSF of 4 patients with atypical clinical and and tamoxifen therapy, mental retardation, CSF profiles [11]. In a trial performed to test the achalasia, chronic granulomatous disease, iso- efficacy of BCG vaccination in the prevention of niazid prophylaxis for positive PPD and previ- tuberculosis in the Chingleput district of ous laminectomy. Madras state, South India, NTM were obtained Therapy included both surgical and antimy- from 8.6% of 16,907 sputum specimens; the cobacterial therapy. The final outcome was con- species isolated most frequently were Mycobac- sidered favorable in 13 (65%) patients. Two pa- terium avium, Mycobacterium terrae and Mycobac- tients died of aspiration pneumonia, and one terium scrofulaceum, while those species ac- other patient died of cor pulmonale. counting for 8-5% of all NTM were Mycobac- Two patients were able to walk with aid, in one terium fortuitum, Mycobacterium chelonae, My- patient there was evidence of persistent lower cobacterium gordonae, and back pain, and one other patient suffered from Mycobacterium flavescens [12]. persistent leg weakness. The detection of Mycobacterium flavescens from Chan ED et al. described three patients with a variety of clinical specimens obtained from vertebral osteomyelitis that was precipitated by patients with HIV infection has also been de- blunt trauma to the back, in the absence of pen- scribed in a few reports [13-15]. etrating trauma, disseminated disease, or the The results of a retrospective survey concerning use of immunosuppressive therapies. These au- atypical cutaneous mycobacterioses contracted thors suggested that, in these cases, the predis- from acquariums, swimming pools and as a re- posing factor was seeding of the mycobacteria sult of mesotherapy, showed that the into an area of recent trauma, which illustrates pathogens most commonly identified among the principle of locus minoris resistentiae, validat- the 92 cases observed included Mycobacterium ing the concept of traumatized tissue being marinum, Mycobacterium chelonae and Mycobac- more vulnerable to invasive infection [5]. terium avium-intracellulare, while Mycobacterium No evidence of predisposing factors for NTM flavescens was rarely identified [9]. osteomyelitis was evident in three patients. Mycobacterium flavescens has been isolated from The case of a Mycobacterium xenopi vertebral os- tuberculosis lesion found in buffaloes exam- teomyelitis in a patient on HAART with a ined during routine post-mortem inspection at CD4+ count of 490 cells/mm3 and viral load be- 2 export abattoirs in Australia [16]. Moreover, low the level of detection at the time of diagno- Mycobacterium flavescens and other NTM were sis has been recently reported [7]. Our patient isolated from raw milk in several studies [17, had diabetes mellitus and a severe chronic is- 18]. chemic cardiopathy, but the presumed source In a study investigating the prevalence of envi- of infection remains unknown. To the best of ronmental mycobacteria in drinking water sup- our knowledge, we describe here the first re- ply systems in a demarcated region in Czech re- ported case of vertebral osteomyelitis due to public Mycobacterium gordonae and Mycobac- Mycobacterium flavescens. Mycobacterium terium flavescens were the most common cul- flavescens is a rapidly growing, scotochro- tured and identified species [19]. mogenic mycobacterium considered as an envi- Biofilms are an important habitat and site for ronmental saprophyte [3]. It rarely causes hu- proliferation of acquatic mycobacteria, includ- man infection and generally is considered as a ing Mycobacterium flavescens. Biofilms may ac- contaminant when isolated from clinical speci- count for the problem of controlling mycobac- mens. terial contamination of water distribution sys- A literature search with the use of Medline and tems by means of chemical disinfection [20]. a subsequent review of articles referenced in Mycobacterium flavescens has also been identi- identified articles revealed few reports of respi- fied in biofilm samples from the waterlines of ratory and cutaneous diseases caused by My- dental units [21]. Mycobacterial proliferation in cobacterium flavescens, and one case of dissemi- biofilms forming within dental units may ex- nated infection involving soft tissues, joints, plain the extent of NTM contamination of den- bones and lungs in a diabetic Chinese male tal spray and cooling water.

99 2003 In summary, our study has stressed the impor- men for rapidly growing NTM infections is tance of recent reports that have described the complicated by their frequent resistance to occurrence of vertebral osteomyelitis due to common antituberculous drugs. non-tuberculous mycobacteria, recognized Thus, therapy with more than one drug should with an increasing incidence among immuno- be employed to increase efficacy and avoid the competent hosts. development of resistance; the best regimen Management of vertebral osteomyelitis due to used is influenced by the results of susceptibil- NTM infection often requires both surgical ity studies on the species identified and the un- débridement and drug therapy. The best treat- derlying medical conditions of the patient be- ment for infections due to rapidly growing my- ing treated. cobacteria is controversial; however, patients Chemotherapeutic regimens for joint and bone may respond well to an appropriate treatment, disease must be prolonged with the use of mul- in cases of non-visceral associated disease due tiple drugs with a regular monitoring of poten- to NTM. Designing the ideal therapeutic regi- tial side effects.

SUMMARY

The aim of this paper is to describe a rare tice. This study stressed the importance of case of vertebral osteomyelitis caused by recent reports that describe the occurrence Mycobacterium flavescens in an immunocom- of vertebral osteomyelitis due to non-tuber- petent patient. Mycobacterium flavescens is a culous mycobacteria that have also been rec- rapidly growing, pigmented, non-tubercu- ognized with an increasing incidence among lous mycobacterium, usually described as immunocompetent hosts. A brief review of non-pathogenic for humans but occasionally the current literature on human disease reported as the cause of serious infectious caused by Mycobacterium flavescens is also re- complications recognized in clinical prac- ported.

RIASSUNTO

L’obiettivo dell’articolo è quello di descrivere un sticate nella pratica clinica. Lo studio riportato ha raro caso di osteomielite vertebrale causato da stressato l’importanza delle recenti descrizioni di Mycobacterium flavescens in un paziente immu- casi di osteomielite da micobatteri non-tubercolari nocompetente. Mycobacterium flavescens è un descritti in maniera crescente anche in ospiti im- micobatterio non-tubercolare, incluso nel gruppo munocompetenti. L’analisi si completa di una dei micobatteri a crescita rapida, pigmentato, breve rassegna sui casi di complicanze infettive da usualmente non patogeno per l’uomo ma occasio- Mycobacterium flavescens riportate in lettera- nalmente responsabile di infezioni gravi diagno- tura.

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