AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Mycobacterium marinum is an atypical Mycobacterium found in salt and fresh water. M marinum is the most common atypical Mycobacterium to cause infection in humans. Infection occurs following primary inoculation of a skin abrasion or puncture and manifests as a localized granuloma or sporotrichotic lymphangitis. Diagnosis and treatment are often delayed because of a lack of suspicion for mycobacterial involvement, ie, versus more common bacterial pathogens.

Pathophysiology

M marinum infection occurs following trauma to an extremity that is in contact with an aquarium, salt water, or marine animals such as fish or turtles. Exposure to M marinum via swimming pools is rare because most pools are chlorinated.

The pathogen is classified in Runyon group 1 and is a photochromogen, which means it produces yellow pigment when cultured and exposed to light. Culture growth occurs over 7-21 days and is optimal at 25-32°C (77-89.6°F) because the organism is adapted to infect ectotherms, such as fish. Endotherms, such as humans, also can be infected; however, the cooler extremities are affected more often than central sites. Systemic infection, usually in the context of an immunocompromised host, has been reported. This indicates that the organism is capable of adapting to grow in conditions closer to 37°C.

After inoculation into the host tissues via an abrasion or other wound, the mycobacteria are phagocytosed by macrophages. Inside the macrophage, they are able to interrupt the formation of the phagolysosome, which would kill the organisms. The mycobacteria then escape the lysosome and can move intracellularly and extracellularly via actin-based motility. This may contribute to cell-to-cell spread.

Studies have revealed 2 pathophysiologically and genetically (ie, via amplified restriction-based polymorphism analysis) distinct populations of M marinum. One group can infect humans and causes acutely lethal disease in fish, while a second group cannot infect humans and causes chronic progressive disease in fish.

Frequency

United States

Infections caused by M marinum are rare but well described in the literature. The estimated annual incidence is 0.27 cases per 100,000 adult patients. Of the approximately 150 cases described, most are case reports of cutaneous infection; however, some describe osteomyelitis, tenosynovitis, arthritis, and disseminated infection. Nosocomial infection has never been described.

International

Infection occurs worldwide, most commonly in individuals with occupational and recreational exposure to fresh or salt water.

Mortality/Morbidity

The disease typically remains localized and does not cause significant morbidity in patients who are immunocompetent. Cases reported in patients who are severely immunocompromised have resulted in disseminated infection involving the bone marrow and viscera and may result in death.

Race

No racial predilection is apparent.

Sex

No sexual predilection has been noted.

Age

M marinum infection has been reported in persons of every age group; however, it appears to be rare in the pediatric population.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Patients at risk include anglers, oyster workers, swimmers, aquarium workers, and individuals with aquariums in their homes.
• Patients may present with a papule, nodule, or ulcer at the site of trauma and a history of exposure to nonchlorinated water 2-3 weeks earlier. Patients may give a history of a papule or nodule that subsequently ulcerated and/or (1) signs of the infection spreading up the finger or hand or (2) involvement of the local joint or tendons. Over a period of months, localized cutaneous disease can spread to soft tissues.
• Localized pain and induration are common. Fever, lymphadenopathy, and systemic infection are rare, with the exception of in immunosuppressed patients.

Physical

• An erythematous or bluish 0.5- to 3-cm papule or nodule develops at the inoculation site, which is the upper extremity in 90% of cases. Ulceration can occur later, and subsequent lesions may be present along the path of lymphatic drainage of the extremity. This occurs in 25-50% of patients and is termed sporotrichotic spread.
• Lymphadenopathy may be present.
• Patients may have deeper involvement, with tenosynovitis bursitis, septic arthritis, and osteomyelitis of the underlying bone. Dissemination to the bone marrow and abdominal viscera is rare.
• If diagnosis is delayed, the infections can mimic rheumatoid arthritis, gout, trauma-related tenosynovitis, foreign body, deep fungal infections, or malignancy.

Causes

The cause is infection with M marinum.

• Exposure of traumatized skin to affected aqueous environments (fish tanks) is the leading predisposing factor.
• Individuals who are consistently exposed to the organism are more likely to develop the infection.
• Hosts who are immunocompromised are also at increased risk.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Infection with atypical mycobacteria (eg, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium avium-intracellulare)
Botryomycosis (Staphylococcus aureus)
Deep fungal infection (eg, with Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis, or Blastomyces dermatitis)
Dematiaceous fungi (chromomycoses)
Infection with Francisella tularensis
Rheumatoid arthritis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Cultures at 25-32°C (77-89.6°F) may grow nonmotile acid-fast bacilli in 7-21 days. The organisms are photochromogens (Runyon group 1), producing yellow pigment only when exposed to light. No niacin or nitrate production occurs; urease is produced, but the organism is a weak producer of catalase at 25°C (77°F).
• If culture results are negative but the history and clinical findings are consistent with M marinum infection, then treatment should still be strongly considered; additionally, performing a biopsy on the lesion may help identify the organisms.

Imaging Studies

• Radiography of the infected area may help evaluate for osteomyelitis.
• Consider CT scanning or MRI of the infected area if tenosynovitis or deeper infection is suspected. MRI may show exuberant tenosynovitis; however, unlike with purulent tenosynovitis, the underlying muscles and bony structures are rarely involved.

Other Tests

• Polymerase chain reaction studies of tissue may help distinguish the exact Mycobacterium species involved. Errors of identification, specifically speciation, have been reported when using PCR.
• Mycobacteriophages are viruses that infect Mycobacterium. They are currently commercially available but are still being refined as a tool to rapidly identify the specific species in mycobacterial infections. They are also being developed as a future modality for treatment of these infections.

Procedures

• Biopsy samples from cutaneous lesions or from intra-articular tissue should be obtained for histopathologic analysis. Acid-fast preparations, such as Ziehl-Neelsen and Fite stains, reveal acid-fast bacilli.
• Surgical drainage of skin lesions often is unnecessary; however, if a deeper infection is diagnosed, drainage may be indicated.

Histologic Findings

The histopathologic findings vary depending on the duration of existence of the lesion sample obtained at biopsy. Early lesions show a nonspecific mixed inflammatory infiltrate, but acid-fast stains typically reveal bacilli. Established lesions display characteristic tuberculoid granulomas, often containing a stellate abscess. Although caseation is rare, the areas of necrosis in the center of the granulomas demonstrate an irregular cavity filled with neutrophils and sometimes demonstrate acid-fast bacilli. The epidermis frequently shows papillomatosis, hyperkeratosis, ulceration, and an acute inflammatory infiltrate.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Treatment is usually medical in nature, using bacteriocidal agents. The duration of therapy is empiric, with recommendations to continue therapy for 4-6 weeks following clinical resolution of the lesions. Treatment of some infections may last as long as 25 months or longer. Spontaneous resolution has been reported.

Surgical Care

Debridement is necessary when infection involves the tendon sheaths, causes persistent pain, or produces a discharging sinus. Surgical drainage of most skin lesions often is unnecessary.

Consultations

A variety of specialists may be involved in the diagnosis and treatment, such as dermatologists, rheumatologists, and infectious disease physicians.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The mainstay of therapy for infection by M marinum is antimicrobials. Most strains of M marinum have been found to be resistant to the antituberculosis medications isoniazid, streptomycin, and para-aminosalicylic acid. The organism is sensitive to rifampin plus ethambutol, tetracyclines, trimethoprim-sulfamethoxazole (TMP-SMZ), clarithromycin, and fluoroquinolones. The duration of therapy is empiric, with recommendations to continue therapy for 4-6 weeks following clinical resolution of lesions.

Drug Category: Antimicrobial agents

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Therapy must be taken regularly and continued for a sufficient period.

Drug Name	Ethambutol (Myambutol)
Description	Only effective when combined with another antimicrobial agent, preferably rifampin. Diffuses into actively growing mycobacterial cells (eg, tubercle bacilli). Impairs cell metabolism by inhibiting synthesis of one or more metabolites, which, in turn, causes cell death. No cross-resistance demonstrated. Mycobacterial resistance is common with previous therapy.
Adult Dose	25 mg/kg/d PO; not to exceed 2500 mg/d
Pediatric Dose	<13 years: Not recommended >13 years: Administer as in adults
Contraindications	Documented hypersensitivity; optic neuritis (unless clinically indicated)
Interactions	Aluminum salts may delay and reduce absorption (give several hours before or after ethambutol dose)
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Reduce dose in impaired renal function; may have adverse visual effects, which may be reversible if promptly discontinued (physical examination should include ophthalmoscopy, finger perimetry, and color discrimination testing); elevated serum uric acid levels occur; precipitation of acute gout has been reported

Drug Name	Minocycline (Dynacin, Minocin) or Doxycycline (Doryx, Vibramycin)
Description	Effective monotherapy; however, strains of M marinum resistant to doxycycline but sensitive to minocycline have been reported. Also treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma species.
Adult Dose	100 mg PO bid
Pediatric Dose	<8 years: Not recommended >8 years: 4 mg/kg PO initially, followed with 2 mg/kg q12h
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with doxycycline but is unusual with minocycline; reduce dose in renal impairment; tetracycline use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines; hepatitis or lupuslike syndromes may occur.

Drug Name	Trimethoprim and sulfamethoxazole (Bactrim, Septra)
Description	Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Several case reports have shown effectiveness of this drug. Reports indicate that it can help eradicate organisms unresponsive to either antituberculars or tetracyclines.
Adult Dose	160 mg TMP/800 mg SMZ PO q12h for 10-14 d
Pediatric Dose	<2 months: Not recommended >2 months: 15-20 mg TMP/kg/d PO in 3-4 divided doses for 14 d
Contraindications	Documented hypersensitivity; megaloblastic anemia due to folate deficiency
Interactions	May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly patients; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in pregnancy or breastfeeding; discontinue at first appearance of rash or sign of adverse reaction; obtain CBC counts frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged intravenous infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, long-term alcoholism, elderly patients, anticonvulsant therapy, malabsorption syndrome); hemolysis may occur in individuals with G-6-PD deficiency; patients with AIDS may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation

Drug Name	Clarithromycin (Biaxin)
Description	Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Has bactericidal activity against atypical Mycobacterium species (eg, M marinum). Cases of organisms resistant to conventional antitubercular therapy have responded to clarithromycin but not erythromycin. Use of azithromycin has not been reported.
Adult Dose	500 mg PO bid
Pediatric Dose	15 mg/kg PO divided bid
Contraindications	Documented hypersensitivity; coadministration of pimozide or cisapride
Interactions	Toxicity increases with coadministration of fluconazole or pimozide; effects decrease and adverse GI effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, or HMG CoA-reductase inhibitors; serious cardiac arrhythmias may occur with coadministration of cisapride; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increase in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Coadministration with ranitidine or bismuth citrate not recommended with CrCl <25 mL/min; give half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies

Drug Name	Ciprofloxacin (Cipro)
Description	Fluoroquinolones are effective alone or in combination with other medications to eradicate M marinum. Inhibits bacterial DNA synthesis and, consequently, growth.
Adult Dose	500 mg PO bid
Pediatric Dose	<18 years: Not recommended >18 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Severe hypersensitivity reactions characterized by rash, fever, eosinophilia, jaundice, and hepatic necrosis with fatal outcome rarely occur; tendon ruptures requiring surgical repair or prolonged disability have been reported; crystalluria rarely occurs because human urine is usually acidic; alkalinity of urine should be avoided; may cause nervousness, agitation, insomnia, anxiety, nightmares, or paranoia; moderate-to-severe phototoxicity manifested as an exaggerated sunburn reaction can occur if directly exposed to sunlight; fatal reactions may occur when coadministered with theophylline

Drug Name	Levofloxacin (Levaquin)
Description	For treatment of tuberculosis and some atypical mycobacterial infections in combination with rifampin and other antituberculosis agents.
Adult Dose	500-1000 mg PO qd or divided bid
Pediatric Dose	<18 years: Not recommended >18 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Patients can be treated in an outpatient setting and should be seen frequently until they begin to respond to therapy, then less frequently until the infection is fully cured. Patients may benefit from seeing an infectious disease physician in an outpatient setting.

Deterrence/Prevention

• People who work near or in salt water should take precautions to avoid abrasions, trauma, or bites from fish and marine animals.
• People who work with aquariums should wear gloves if they are cleaning tanks or expect to encounter trauma to their hands or feet.
• If bites or abrasions occur, cleanse the skin, apply an antibacterial preparation, and dress with an appropriate bandage.

Complications

• Persistent ulceration
• Osteomyelitis, bony erosion
• Bursitis
• Tenosynovitis
• Arthritis
• Disseminated infection

Prognosis

• Once identified and appropriately treated, M marinum infection can typically be successfully eradicated, usually with no major sequelae.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Sporotrichosis is most commonly associated with nodular lymphangitis. For this reason, M marinum infection can often be misdiagnosed as sporotrichosis. Patients sometimes undergo long courses of antifungal treatments before further spreading of the Mycobacterium elicits a repeat biopsy and culture.
• Involved joints may be misdiagnosed as inflammatory arthritis, and the joint may be inappropriately injected with a corticosteroid. Corticosteroid injection can result in marked progression of the disease.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Arai H, Nakajima H, Kaminaga Y. In vitro susceptibility of Mycobacterium marinum to dihydromycoplanecin A and ten other antimicrobial agents. J Dermatol. Jun 1990;17(6):370-4. [Medline].
• Bhatty MA, Turner DP, Chamberlain ST. Mycobacterium marinum hand infection: case reports and review of literature. Br J Plast Surg. Mar 2000;53(2):161-5. [Medline].
• Cummins DL, Delacerda D, Tausk FA. Mycobacterium marinum with different responses to second-generation tetracyclines. Int J Dermatol. Jun 2005;44(6):518-20. [Medline].
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• Lam A, Toma W, Schlesinger N. Mycobacterium marinum arthritis mimicking rheumatoid arthritis. J Rheumatol. Apr 2006;33(4):817-9. [Medline].
• Ljungberg B, Christensson B, Grubb R. Failure of doxycycline treatment in aquarium-associated Mycobacterium marinum infections. Scand J Infect Dis. 1987;19(5):539-43. [Medline].
• Mahaisavariya P, Chaiprasert A, Manonukul J, et al. Detection and identification of Mycobacterium species by polymerase chain reaction (PCR) from paraffin-embedded tissue compare to AFB staining in pathological sections. J Med Assoc Thai. Jan 2005;88(1):108-13. [Medline].
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• Nolte O, Haag H, Häfner B. A mutation in the 65,000 Dalton heat shock protein gene, commonly used for molecular identification of non-tuberculous mycobacteria, leads to the misidentification of Mycobacterium malmoense as Mycobacterium marinum. Mol Cell Probes. Aug 2005;19(4):275-7. [Medline].
• Noonburg GE. Management of extremity trauma and related infections occurring in the aquatic environment. J Am Acad Orthop Surg. Jul-Aug 2005;13(4):243-53. [Medline].
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• Posteraro B, Sanguinetti M, Garcovich A, et al. Polymerase chain reaction-reverse cross-blot hybridization assay in the diagnosis of sporotrichoid Mycobacterium marinum infection. Br J Dermatol. Nov 1998;139(5):872-6. [Medline].
• Ryan JM, Bryant GD. Fish tank granuloma--a frequently misdiagnosed infection of the upper limb. J Accid Emerg Med. Nov 1997;14(6):398-400. [Medline].
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Article Last Updated: Sep 8, 2006