Invasive Mycobacterium marinum infections.

To the Editor: Mycobacterium marinum infections, commonly known as fish tank granuloma, produce nodular or ulcerating skin lesions on the extremities of healthy hosts. Delay of diagnosis is common, and invasion into deeper structures such as synovia, bursae, and bone occurs in approximately one third of reported case-patients (1).

A 49-year-old man with diabetes, who had received a kidney transplant from a living relative 8 years previously, sought treatment after 5 months of worsening swelling and tenderness of the left elbow. Of note, he had injured his left ring finger while cleaning barnacles from a piling 5 years previously and had contracted a secondary infection that never completely healed despite three courses of antimicrobial drugs and surgical debridement. Physical examination showed marked swelling, tenderness, and warmth of the left elbow, as well as of the left ring finger, which was erythematous. Sterile aspiration of the olecranon bursa showed 7,500 leukocytes (62% lymphocytes) and 141,000 erythrocytes. Results of Gram stain and routine cultures were negative. Magnetic resonance imaging of the left arm showed soft tissue edema of the olecranon bursa and the left fourth flexor digitorum longus tendon, and no osteomyelitis. Three weeks later, olecranon bursa aspirate fluid cultures incubated on chocolate agar and 7H11 plates at 31[degrees]C, as well as on algae slant, and mycobacterial growth indicator tubes incubated at 37[degrees]C grew Mycobacterium marinum. The isolate was susceptible to most agents but showed intermediate susceptiblity to ciprofloxacin (MIC 2 [micro]g/mL) and was resistant to ampicillin/clavulanate and erythromycin (MIC 8 [micro]g/mL and 32 [micro]g/mL, respectively). A treatment regimen of rifampin and ethambutol was begun, and the patient showed a dramatic improvement in the ensuing several weeks. The patient has completed 9 of 11.4 planned months of therapy and continues to do well, with frequent office visits.

Case reports from English language MEDLINE articles since 1966 under the subject heading Mycobacterium marinum were cross-referenced with articles containing the following text words: disseminated, osteomyelitis, arthritis, synovitis, and bursitis. Ten case reports were identified, and a hand search through pertinent articles' references yielded 13 additional reports. A total of 35 cases of invasive M. marinum disease were then reviewed, according to patient age and sex, symptoms, source of infection, immune impairment, time to diagnosis, and type as well as duration of therapy (2-24) (see online Table at http://www.cdc.gov/ncidod/EID/vo19no11/03-0192.htm#table).

Most cases occurred in previously healthy adults. The average age was 43 years; 24 (69%) were men; 21 (60%) had tenosynovitis; 6 (17%) had septic arthritis; and 13 (37%) had osteomyelitis. In three patients (9%), either a bone marrow or blood culture positive for M. marinum was obtained; all three patients showed marked systemic immunocompromise. Multiple skin lesions were seen in 23% of cases; half of these patients showed clear evidence of deeper infection. Some patients had more than one manifestation of invasive disease. Immunologic impairment was a frequent component of invasive M. marinum infections: 14 (40%) of case-patients received a steroid injection at the site of infection, and 9 (26%) were receiving systemic steroids for various indications. An additional 4 (11%) case-patients were in an immunocompromised state from other sources such as chemotherapy or AIDS. Delayed diagnosis was also a prominent finding: The average time to diagnosis was 17 months from symptom onset. The treatment course was prolonged and aggressive: The average treatment duration was 11.4 months in the 20 reports in which a definitive duration was given. Surgery was undertaken in 69% of the cases. The treatment regimen used varied considerably, although 30 (88%) of the 34 patients who took antimycobacterial medications received combination therapy. Rifampin (76%) and ethambutol (68%) were the predominant agents.

While M. marinum infections usually arise from aquatic trauma in healthy hosts, delayed diagnosis and immune suppression contribute to the pathogenesis of invasive infection. Tenosynovitis is the most common manifestation of deep invasion, although septic arthritis and osteomyelitis are well described. Disseminated skin lesions can accompany deeper invasion but may be seen in isolation as well. Bone marrow invasion and bacteremia are rare and have been seen only in profoundly immunocompromised patients.

Although the rarity of the condition makes estimating its incidence difficult, the number of case reports per year has remained stable for the last 30 years. However, the high frequency of delayed diagnosis in cases of invasive M. marinum disease underscores the importance of maintaining a high level of suspicion for this condition, especially in patients who have evidence of previous aquatic trauma or refractory soft tissue infections. Further, since immunosupression was common in cases of invasive disease, local steroid injections should be avoided in patients with soft tissue infection after aquatic trauma at least until M. marinum infection is ruled out by acid-fast staining or mycobacterial culture of biopsy specimens or fluids.

Once invasive M. marinum disease was diagnosed, patients with invasive disease were treated for an average of 11.4 months, three times longer than the typical course for M. marinum superficial infections (1). Rifampin and ethambutol were used most often in invasive infections, although many therapeutic choices exist. In a study of 61 clinical isolates, rifamycins and clarithromycin were the most potent, with the lowest MICs, and resistance was uncommon. Doxycycline, ethambutol, and minocycline all showed higher MICs but were still effective (1). A different group tested 11 agents against 37 clinical isolates and found that trimethoprim/sulfamethoxazole was the most potent agent, but 92% of isolates were susceptible. Clarithromycin and minocycline, by contrast, showed susceptibility rates approaching 100% and retained similar potency (25). This study reported an MI[C.sub.50] for most quinolones of 4 [micro]g/mL or higher, although in a different study, 100% of M. marinum isolates were susceptible to gatifloxacin (26). Approximately three fourths of isolates in this latter study were susceptible to ciprofloxacin and levofloxacin. Among newer antibiotics tested against M. marinum in this series, only linezolid showed much promise (26). On the basis of the sparse data correlating susceptibility testing results to clinical response, and the relative infrequency of resistance, recent guidelines suggest foregoing susceptibility testing in M. marinum infections unless the infection does not respond to treatment (27). Most cases of invasive M. marinum infection require surgical debridement, 69% in this series. This approach seems particularly appropriate in immunocompromised patients, those with tenosynovitis, or those for whom medical therapy fails.

References

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(18.) Shih J, Hsueh P, Chang Y, Chen M, Yang P, Luh K. Osteomyelitis and tenosynovitis due to Mycobacerium marinum in a fish dealer. J Formos Med Assoc 1997;96:913-6.

(19.) Gatt R, Cushieri P, Sciberras C. An unusual case of flexor sheath tenosynovitis. J Hand Surg [Br] 1998;23:698-9.

(20.) Ekerot L, Jacobsson L, Forsgren A. Mycobacerium marinum wrist arthritis: local and systematic dissemination caused by concomitant immunosuppressive therapy. Scand J Infect Dis 1998;30:84-7.

(21.) Holmes GF, Harrington SM, Romagnoli MJ, Merz WG. Recurrent disseminated Mycobacerium marinum infection caused by the same genotypically defined strain in an immunocompromised host. J Clin Microbiol 1999;37:3059-61.

(22.) Thariat J, Leveque L, Tavernier C, Maillefert .IF. Mycobacerium marinum tenosynovitis in a patient with Still's disease. Rheumatology 2001;40:1419-20.

(23.) Ho P, Ho P, Fung BK, Ip W, Wong SS. A case of disseminated Mycobacerium marinum infection following systemic steroid therapy. Scand J Infect Dis 2001;33:232-3.

(24.) Enzensberger R, Hunfeld K, Elshorst-Schmidt T, Boer A, Brade V. Disseminated cutaneous Mycobacerium marinum infection in a patient with non-Hodgkin's lymphoma. Infection 2002;30:393-5.

(25.) Rhomberg PR, Jones RN. In vitro activity of 11 antimicrobial agents, including gatifloxacin and GAR936, tested against clinical isolates of Mycobacterium marinum. Diagn Microbiol Intact Dis 2002;42:145-7.

(26.) Braback M, Riesbeck K, Forsgren A. Susceptibilities of Mycobacterium marinum to gatifloxacin, gemifloxacin, levofloxacin, linezolid, moxifloxacin, telithromycin, and quinupristin-dalfopristin (Synercid) compared to its susceptibilities to reference macrolides and quinolones. Antimicrob Agents Chemother 2002; 46:1114-6.

(27.) Woods G Susceptibility testing for mycobacteria. Clin Infect Dis 2000;31:1209-15.

Address for correspondence: Timothy Lahey, Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, One Autumn Street, Kennedy-6, Boston, MA 02215, USA; fax: [phone]; email: [e-mail]

Timothy Lahey *

* Harvard Medical School, Boston, Massachusetts, USA