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Letter
Invasive Mycobacterium
marinum Infections
Timothy Lahey*
*Harvard Medical School, Boston, Massachusetts, USA
Suggested citation
for this article:
Lahey T. Invasive Mycobacterium marinum infections. Emerg Infect
Dis [serial online] 2003 November [date cited]. Available from:
URL: http://www.cdc.gov/ncidod/EID/vol9no11/03-0192.htm
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°C, as well as on algae slant, and mycobacterial growth indicator tubes
incubated at 37°C grew M.ycobacterium marinum. The isolate was
susceptible to most agents but showed intermediate susceptiblity to ciprofloxacin
(MIC 2 mg/mL) and was resistant to ampicillin/clavulanate and erythromycin
(MIC 8 mg/mL and 32 mg/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) (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 MIC50 for most
quinolones of 4 mg/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.
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Sixty-three
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Mycobacerium marinum infection and bacteremia in a child with
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and tenosynovitis due to Mycobacerium marinum in a fish dealer.
J Formos Med Assoc 1997;96:913–6.
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Table.
Summary of Invasive Mycobacterium marinum infection cases published
since 1966 |
|
Ref.
|
Age
|
Sex
|
Symptoms
|
Source
|
Immune impairment
|
Dx delay (mo)
|
Medications
|
Surgery ?
|
Treatment duration (mo)
|
|
(2)
|
32
|
M
|
Disseminated cutaneous, larynx
|
Minor trauma
|
Systemic steroids
|
240
|
I, S
|
Yes
|
>36
|
(3)
|
37
|
M
|
R middle finger osteomyelitis
|
Fishing injury
|
Local steroid injection
|
3
|
Erythromycin, S
|
Yes
|
5
|
(3)
|
30
|
M
|
R long finger osteomyelitis
|
Minor trauma
|
None
|
12
|
Declined
|
No
|
--
|
(3)
|
56
|
M
|
R ring finger tenosynovitis
|
Minor trauma, fishing
and cleaning boats
|
Local steroid injection
|
1.2
|
E
|
Yes
|
9
|
(3)
|
52
|
M
|
L index finger osteomyelitis
and synovitis
|
None
|
Local steroid injection
|
7
|
Cycloserine, ethionamide, R
|
Yes
|
?
|
(3)
|
60
|
M
|
R ring finger synovitis and
osteomyelitis
|
Shrimp cleaning injury
|
None
|
7
|
E, R
|
Yes
|
6
|
(3)
|
55
|
M
|
L long finger synovitis and
skin ulcer
|
Shrimp cleaning injury
|
None
|
23
|
E
|
Yes
|
6
|
(4)
|
30
|
M
|
Disseminated skin nodules,
lymphangitis
|
Aquarium cleaning
|
Systemic steroids and
azathioprine for renal
transplant
|
2
|
E, R, T
|
No
|
?
|
(5)
|
1.3
|
F
|
Disseminated cutaneous nodules
|
Aquarium exposure
|
None
|
2
|
E, I, R
|
No
|
8
|
(6)
|
26
|
M
|
R hand tenosynovitis
|
Fisherman
|
Local steroid injection
|
8
|
E, P, R, tetracycline
|
Yes
|
?
|
(6)
|
45
|
M
|
R index tenosynovitis
|
Saltwater fishing
|
Local steroid injection
|
1
|
E, R, tetracycline
|
Yes
|
?
|
(6)
|
22
|
M
|
R hand tenosynovitis
|
Fisherman
|
None
|
2
|
I, R, S
|
Yes
|
?
|
(6)
|
56
|
F
|
L hand tenosynovitis
|
Fishing injury
|
Local steroid injections
|
5
|
I, R, S
|
Yes
|
?
|
(6)
|
53
|
M
|
R hand and forearm synovitis,
bursitis
|
Fisherman
|
Local steroid injections
|
78
|
E, I, R, S
|
Yes
|
?
|
(7)
|
47
|
F
|
R hand tenosynovitis and
osteomyelitis
|
None
|
None
|
1
|
E, I, R
|
Yes
|
?
|
(8)
|
32
|
M
|
L hand tenosynovitis
|
None
|
Local steroid injection
|
1
|
E, R, sulfamethoxazole
|
Yes
|
24
|
(8)
|
42
|
M
|
L hand tenosynovitis
|
Shrimp fishing
|
None
|
3
|
E, I, R
|
Yes
|
24
|
(8)
|
52
|
F
|
R hand tenosynovitis
|
Shrimp spine injury
|
None
|
1
|
D, E, R
|
No
|
24
|
(8)
|
31
|
F
|
L index finger tenosynovitis
|
Crab bite
|
Local steroid injection
|
6
|
D, E, R
|
Yes
|
24
|
(9)
|
56
|
M
|
L index finger osteomyelitis
and wrist synovitis
|
Fisherman
|
Local steroid injections
|
12
|
E, M, R
|
Yes
|
9
|
(10)
|
5
|
M
|
Polyarthritis, disseminated
skin lesions, hepatic function
abnormalities
|
None
|
Abnormalities in monocyte
function
|
48
|
A, clofazamine, E, R, T
|
No
|
9
|
(11)
|
35
|
F
|
L hand and wrist septic arthritis,
cutaenous lesions on arm
|
Puffer fish sting
|
Systemic steroids for SLE
flares
|
18
|
M
|
No
|
>12
|
(12)
|
62
|
F
|
L middle finger osteomyelitis
with skin nodules
|
Injury while gardening,
owned tropical fish aquarium
|
None
|
8
|
E, R
|
Yes
|
4
|
(13)
|
33
|
M
|
R hand nodules, LAD, pneumonia,
bacteremia
|
Fish tank
|
AIDS (CD4<5)
|
0.5
|
C, clofazimine, ethionamide
|
Yes
|
3 until death
|
(14)
|
56
|
M
|
L ring finger septic arthritis,
osteomyelitis
|
Minor trauma, fish tank
|
Local steroid injection
|
2
|
C, E, R
|
No
|
12
|
(15)
|
0.25
|
M
|
Diffuse pustules, osteomyelitis,
bacteremia
|
Bathed in bathtub in
which fishtank washed
|
SCID
|
?
|
I, R, T
|
No
|
6 until death
|
(16)
|
71
|
M
|
R 2nd MCP synovitis, septic
arthritis, osteomyelitis
|
Swimming and fishing injury
|
Local steroid injection
|
9
|
C, E, I, R
|
Yes
|
12
|
(17)
|
48
|
F
|
L hand osteomyelitis, R forearm cutaneous
lesions, R ankle septic arthritis and osteomyelitis
|
Fish tank cleaning
|
Cyclosphosphamide and
systemic steroids for
polymyositis
|
10
|
D, I pyrazinamide, R
|
Yes
|
5
|
(18)
|
52
|
F
|
R hand tenosynovitis and
osteomyelitis
|
Fish dealer, puncture injury
|
Systemic steroids and
local herbal injections
|
2
|
Clarithromycin, D, E, I, R
|
Yes
|
18
|
(19)
|
41
|
F
|
R index flexor sheath tenosynovitis
|
Fishmonger
|
Local steroid injection
|
3
|
M
|
Yes
|
1.5
|
(20)
|
53
|
M
|
R middle finger tenosynovitis,
septic arthritis, wrist osteomyelitis,
discharging sinuses
|
Nonpenetrating trauma,
home aquarium
|
Local steroid injections,
systemic methotrexate
|
24
|
C, E, R, S
|
No
|
13
|
(21)
|
81
|
M
|
L forearm plaque, L index finger
ulcer, R forearm cellulitis, bone
marro cx + pancytopenia
|
Aquarium exposure
|
Systemic steroids and
azathioprine for myasthenia
gravis
|
5
|
C, D
|
No
|
<1 before death
|
(22)
|
22
|
M
|
R wrist tenosynovitis, nodular
skin lesions
|
“Fish-related hobby”,
aquarium
|
Systemic steroids for Still’s
disease
|
0.25
|
C, clarithromycin, E, R
|
Yes
|
4
|
(23)
|
70
|
M
|
R hand and wrist tenosynovitis,
subcutaneous nodules, L knee
septic arthritis
|
Fish fin wound
|
Systemic steroids
|
12
|
A, E, M, R
|
Yes
|
12
|
(24)
|
60
|
F
|
Disseminated ulcerating abscesses
|
Tropical aquarium
|
Systemic steroids and
chemotherapy for non-Hodgkin
lymphoma
|
8
|
clarithromycin, clotrimazole,
E, immunoglobulins, levofloxacin,
R, S,
|
No
|
?
|
|
aDx,
diagnosis; l, left; R, right; MCP,metacarpophalangeal; A, amikacin;
C, ciprofloxacin; D, doxycycline; E, ethambutol; I, isoniazid; M,
minocycline; P, pyrazinamide; R, rifampin; S, streptomycin; T, trimethoprim/sulfamethoxazole |
|