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 infection occurs following skin trauma in fresh or salt water and usually presents as a localized granuloma or sporotrichotic lymphangitis. This pathogen is classified in Runyon group 1 and is a photochromogen, which means it produces pigment when cultured and exposed to light. Culture growth occurs over 7-14 days and is optimal at 32°C.

Pathophysiology

M marinum infection occurs following trauma to an extremity that is in contact with an aquarium, salt water, or marine animals. Exposure to M marinum via swimming pools is rare because most pools are chlorinated. The organism grows better at 32°C; therefore, cooler extremities are affected more often than central sites. M marinum rarely disseminates, except in the setting of a severely immunosuppressed patient.

Frequency

United States

Infections caused by M marinum are rare but well described in the literature. 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. M marinum is ubiquitous and is found more often in salt water than in fresh water. Individuals who fish or work with aquariums have an increased risk of exposure. Nosocomial infection has never been described.

International

International incidence and prevalence are unknown due to lack of surveillance.

Mortality/Morbidity

• Infection with M marinum responds slowly to appropriate antibiotic therapy. Patients may require treatment for 2 weeks to as long as 18 months.
• Infection may result in persistent ulceration, draining sinuses, or septic arthritis. Aggressive M marinum infection may cause extensive osteomyelitis and amputation of the involved digit.
• Reports describe dissemination to the bone marrow and visceral involvement; however, the reports do not include deaths directly related to M marinum infection.Patients with acquired immunodeficiency syndrome have been reported to have disseminated M marinum infection.

Race

No known racial predilection exists.

Sex

No known sex predilection exists, and infection in men is linked to occupational exposures.

Age

No known age predilection exists.

CLINICAL

Section 3 of 10  

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

History

• Infection often follows abrasions to an extremity occurring in nonchlorinated water. Fishermen, oyster workers, swimmers, and aquarium workers are predisposed.
• A papule or nodule initially appears at the site of trauma. This nodule subsequently may ulcerate and involve the local joint or tendons.
• Localized pain and induration are common. Fever, localized lymphadenopathy, and systemic infection rarely are observed, with the exception of immunosuppressed patients.
• The incubation period of M marinum is about 2-3 weeks.
• The localized lesion can increase slowly over several months.

Physical

• A papule or bluish nodule develops at the inoculation site. Ulceration can occur later, and subsequent lesions may be present along the path of lymphatic drainage of the extremity.
• In 25-50% of patients, the nodules proliferate along the path of lymphatic drainage in a sporotrichotic type of distribution.
• Patients may have deeper involvement, with tenosynovitis, septic arthritis, and osteomyelitis of the underlying bone. Dissemination to the bone marrow and abdominal viscera rarely develops.
• An upper extremity is affected in nearly 90% of cases. Patients also can present with an erythematous plaque on their hands.
• Most patients have a tuberculin skin test of less than 10 mm of induration.
• The presentation can be similar to that of interstitial granuloma annulare.

Causes

Infection is caused by inoculation with M marinum. Individuals who are at increased risk for infection are as follows:

• Fishermen and workers who process saltwater fish
• Workers who clean saltwater aquariums
• Immunocompromised patients (increased risk of disseminated infection)
• Home aquarium owners

DIFFERENTIALS

Section 4 of 10  

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

WORKUP

Section 5 of 10  

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

Lab Studies

• Cultures may grow nonmotile acid-fast bacilli in 7-14 days, with optimum growth at 32°C.
• The organisms are photochromogen (Runyon group 1), producing 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.
• Even on repeat cultures results may remain negative.
• Polymerase chain reaction (PCR) amplification techniques using Mycobacterium genus-specific primers can be used to diagnose M marinum infection directly in the biopsy sample.

Imaging Studies

• Obtain radiographs of the infected area to evaluate for evidence of osteomyelitis.
• Consider a CT scan or MRI of the infected area if tenosynovitis or deeper infection is suspected.

Procedures

• Surgical drainage of skin lesions often is unnecessary; however, if diagnosing deeper infection, drainage is indicated.

Histologic Findings

Younger lesions show epidermal hyperkeratosis, mixed inflammatory response, or, possibly, frank suppuration. Older lesions may present as organized granulomas; however, caseation is uncommon. Organisms are acid fast and may have a transverse banding pattern.

TREATMENT

Section 6 of 10  

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

Medical Care

Treatment usually is medical with bacteriocidal agents. Duration of therapy is empiric, with recommendations to continue therapy for 4-6 weeks following clinical resolution of lesions. Treatment of some infections may last 18 months or longer. Spontaneous resolution has been reported.

Surgical Care

Surgical drainage of skin lesions often is unnecessary. For deeper infection, drainage is indicated.

Consultations

An infectious disease physician can establish the diagnosis and suggest management.

MEDICATION

Section 7 of 10  

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

Strains of M marinum are resistant to the antituberculosis medications isoniazid, streptomycin, and para-aminosalicylic acid. This organism is sensitive to rifampin, ethambutol, tetracyclines, trimethoprim-sulfamethoxazole (TMP-SMX), clarithromycin, and levofloxacin.

Use clarithromycin (bacteriocidal for M marinum) for initial therapy. Use ethambutol and rifampin together as empiric therapy, particularly in patients older than 6 years. Other clinically effective agents are minocycline, TMP-SMX, and levofloxacin. Duration of therapy is empiric, with recommendations to continue therapy for 4-6 weeks following clinical resolution of lesions. Treatment of some infections may last 18 months or longer. Spontaneous resolution has been reported.

Drug Category: Antimycobacterials

Empiric antimycobacterial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Drug Name	Ethambutol (Myambutol)
Description	Suppresses mycobacteria multiplication by interfering with RNA synthesis. Bacteriostatic against tubercle bacilli.
Adult Dose	No previous antituberculous therapy: 15 mg/kg (7 mg/lb) PO qd as a single dose Previous antituberculous therapy: 25 mg/kg (11 mg/lb) PO qd
Pediatric Dose	Not generally used in children > 6 y who are not able to take visual acuity and color perception tests reliably <13 years: Not recommended >13 years: Administer as in adults
Contraindications	Documented hypersensitivity; presence of optic neuritis (unless clinically indicated)
Interactions	Decreased absorption with aluminum salts (administer several h before or after ethambutol dose)
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Major toxicity of ethambutol is retrobulbar neuritis and peripheral neuropathy; visual field constriction or impairment of acuity or color vision may develop, perform visual acuity and color perception testing q4-6wk while on therapy; reduce dose in impaired renal function

Drug Category: Antimicrobials

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Drug Name	Clarithromycin (Biaxin)
Description	Effective against most strains on nontuberculous mycobacterium species, including M marinum, Mycobacterium avium-intracellulare, M fortuitum, M chelonae, and Mycobacterium abscessus. Exerts antibacterial action by binding to 50S ribosomal subunit, resulting in inhibition of protein synthesis.
Adult Dose	500 mg PO q12h
Pediatric Dose	<6 months: Not established >6 months: 15 mg/kg/d PO divided q12h
Contraindications	Documented hypersensitivity; concurrent use with pimozide
Interactions	Toxicity increases with coadministration of fluconazole and pimozide; clarithromycin effects decrease and GI adverse effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, and HMG CoA-reductase inhibitors; 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 is not recommended with CrCl <25 mL/min; administer 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	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 1-2 h before or after taking fluoroquinolones
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

Drug Name	Azithromycin (Zithromax)
Description	Treats mild-to-moderate microbial infections.
Adult Dose	1 g PO once Day 1: 500 mg PO Days 2-5: 250 mg PO qd
Pediatric Dose	<6 months: Not established >6 months: Day 1: 10 mg/kg PO once; not to exceed 500 mg/d Days 2-5: 5 mg/kg PO qd; not to exceed 250 mg/d
Contraindications	Documented hypersensitivity; hepatic impairment; do not administer with pimozide
Interactions	May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients

Drug Name	Rifabutin (Mycobutin)
Description	Indicated for the treatment of tuberculosis and several atypical mycobacterial infections. If GI upset occurs, administer dose bid with food.
Adult Dose	300-600 mg PO qd; alternatively, 10-20 mg/kg/d; not to exceed 600 mg/d
Pediatric Dose	Not established; suggested dose is 5 mg/kg/d PO
Contraindications	Documented hypersensitivity
Interactions	Steady-state zidovudine plasma levels may decrease after repeated rifabutin dosing but does not affect inhibition of HIV by zidovudine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Do not administer to patients with active tuberculosis; no evidence exists that rifabutin is effective in prophylaxis against Mycobacterium tuberculosis; may administer isoniazid and rifabutin concurrently in patients requiring prophylaxis against both M tuberculosis and M avium complex; perform hematologic studies periodically in patients receiving prophylaxis due to association with neutropenia and, more rarely, thrombocytopenia

FOLLOW-UP

Section 8 of 10  

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

Further Outpatient Care

• Treat patients in an outpatient setting.
• See patients weekly until they begin to respond to therapy, and then biweekly until their infection is fully cured.

In/Out Patient Meds

• Continue clarithromycin or the combination ethambutol plus rifampin until the infection resolves.

Transfer

• Transfer to other facilities is not necessary.
• Refer patients to an infectious diseases physician in an outpatient clinical setting.

Deterrence/Prevention

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

Complications

• Persistent ulceration
• Osteomyelitis
• Tenosynovitis
• Arthritis
• Disseminated infection
• Amputation of involved digit

Prognosis

• With treatment, prognosis is excellent.

Patient Education

• Patients are not infectious and will be cured with proper treatment.
• Educate people who work near salt water to cleanse the skin with an antibacterial preparation and dress with an appropriate bandage if abrasions or bites occur.

MISCELLANEOUS

Section 9 of 10  

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

Medical/Legal Pitfalls

• Failure to accurately identify M marinum as the causative agent - Infection may be mistaken for sporotrichosis
• Failure to obtain appropriate biopsy samples and skin lesion cultures to determine appropriate therapy

Special Concerns

• Infection in patients with the acquired immunodeficiency syndrome may result in dissemination to the bone marrow, liver, spleen, and lung. This infection may be hard to detect in this setting and further may be confused with M tuberculosis. M marinum will not respond to conventional antituberculosis agents, such as isoniazid and para-aminosalicylic acid.

REFERENCES

Section 10 of 10

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

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Article Last Updated: Feb 28, 2006