Mycobacterium marinum Infection

Mycobacterium marinum is an atypical Mycobacterium species found in cold or warm, fresh or salted water. M marinum infection occurs following skin and soft-tissue injuries that are exposed to an aquatic environment or marine animals. The infection usually presents as a localized granuloma but can evolve into an ascending lymphangitis that resembles sporotrichosis or can spread to deeper tissues. M marinum is a pathogen classified in Runyon group 1 and is a photochromogen, meaning it produces pigment when cultured and exposed to light. Culture growth occurs over 7-14 days and is optimal at 32°C. See the image below.

For additional information on cutaneous M marinum infection, see the Medscape Reference article Dermatologic Manifestations of Mycobacterium Marinum Infection of the Skin. 

M marinum is water-borne atypical Mycobacterium species that commonly infects fish and amphibians. It was first recognized to cause human disease in 1951. M marinum infection commonly develops as a complication of skin and soft-tissue injuries exposed to aquatic equipment such as fish lines and fishhooks, among others. Domestic exposures involved in infection commonly involve fish tank manipulations. M marinum infection was once called swimming pool granuloma, but that term is rather obsolete because of the widespread use of chlorination in swimming pools. Chlorinated swimming pools are not considered an exposure risk.[1]

M marinum grows best at 32°C; therefore, cooler extremities, particularly hands, are affected more often than central areas. This feature is also important for optimal growth in the microbiology laboratory. M marinum can disseminate in severely immunosuppressed individuals (eg, transplant recipients).

Frequency

United States

M marinum infections are rare but well described in the literature. The estimated annual incidence is 0.27 cases per 100,000 adult patients. The infection typically is limited to the skin, mostly involving limbs, but spread to deeper structures has been reported. This can result in clinical entities such as tenosynovitis, septic arthritis, and osteomyelitis. Dissemination is extremely rare and has been reported mainly in severely immunocompromised individuals.

M marinum is ubiquitous and is found in both salt and fresh waters. At least 150 fish and frog species, aquatic mammals (eg, dolphins), eels, oysters, African toads, and royal pythons are known to acquire natural M marinum infection. In Africa, M marinum has been isolated from healthy human skin and soil. Individuals who fish or work with aquariums are at an increased risk for exposure. To the authors’ knowledge, nosocomial M marinum infection has never been reported.

International

The international incidence and prevalence of M marinum infection are unknown owing to a lack of surveillance. One French study found the incidence of M marinum infection to be 0.04 per 100,000 inhabitants per year.

Feng et al described an outbreak of a cutaneous M marinum infection in China in 2008.[2]

Mortality/Morbidity

M marinum infection responds slowly to appropriate antibiotic therapy. Infected patients may require treatment for 2 weeks or up to 18 months.

M marinum infection may result in persistent ulceration, draining sinuses, or septic arthritis. Aggressive M marinum infection may cause extensive osteomyelitis, resulting in amputation of the involved digit.

Disseminated M marinum infection and more invasive skin infections have been reported in significantly immunosuppressed individuals. Reports describe dissemination to the bone marrow and visceral involvement; however, the reports do not include deaths directly related to M marinum infection.

Delayed diagnosis can result from the indolent nature of early lesions and a lack of clinical suspicion. The average interval from clinical presentation to correct diagnosis varies from 1-27 months, with a mean interval of 7 months.[3]

Race

M marinum infection has no known racial predilection.

Sex

M marinum infection has no known sexual predilection. Infection in men typically is linked to occupational exposures.

Age

M marinum infection has no known age predilection.

With treatment, M marinum infection carries an excellent prognosis. A study from France reported cure in 87% of cases. Treatment failure was significantly related to deeper-structure involvement and ulcerative skin lesions but not to acquired antimicrobial resistance.

Clinical presentations and outcomes of M marinum infections in patients with HIV infection did not differ from those in patients without HIV infection.

Patients with M marinum infection are not infectious and are cured with proper treatment.

Educate people who work near salt water to cleanse their skin with an antibacterial preparation and to dress abrasions or bites with an appropriate bandage.

M marinum infection often follows abrasions to an extremity occurring in nonchlorinated water. Fishermen, oyster workers, swimmers, and aquarium workers are predisposed to infection.

M marinum has an incubation period of approximately 2-3 weeks

A mildly tender papule or nodule initially appears at the site of trauma, slowly enlarges, and then suppurates or ulcerates.

The localized lesion can grow slowly over several months.

Localized pain and induration are common.

Further nodular lesions may develop along the lymphatic channels, resulting in ascending nodular lymphangitis.

Regional lymphadenitis and systemic symptoms are uncommon.

Contiguous spread to deeper structures (eg, tendons, joints, or even bones) occurs in up to one third of individuals with M marinum infection.

In individuals with M marinum infection, a papule or bluish nodule develops at the inoculation site. Suppuration or ulceration appears at a later stage.

An ascending nodular lymphangitis develops in 25-50% of infected patients. This entity also is seen in other infectious etiologies, especially sporotrichosis, New World cutaneous leishmaniasis, nocardiosis, ulceroglandular form of tularemia, infections with other nontuberculous mycobacteria (eg, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium kansasii), various fungal infections (blastomycosis, histoplasmosis, cryptococcosis, coccidioidomycosis) and several pyogenic bacteria (Staphylococcus aureus, Streptococcus pyogenes, Burkholderia pseudomallei, Bacillusanthracis).

An upper extremity is affected in nearly 90% of persons with M marinum infection, mostly on the hands. See the image below.

Deeper involvement, with tenosynovitis, septic arthritis, and osteomyelitis of the underlying bone, may be evident on examination.

Most patients with M marinum infection have a tuberculin skin test result between 5-9 mm of induration.

M marinum infection may present similarly to interstitial granuloma annulare.[4]

Infection is caused by inoculation with M marinum. Individuals at an increased risk for infection include the following:

• Fishermen and fish-processing workers

• Saltwater aquarium maintenance personnel

• Home aquarium owners

• Immunocompromised individuals

Potential complications include the following:

• Persistent ulceration or suppuration

• Osteomyelitis

• Tenosynovitis

• Arthritis

• Disseminated infection

• Amputation of involved digit

The criterion standard for diagnosis is culture from the tissue biopsy. Cultures have been reported as positive in 70% to 80% of cases. At least a 4-mm skin punch biopsy or multiple biopsy specimens are recommended. M marinum is a nonmotile acid-fast bacillus (AFB) that grows in 2-3 weeks, with optimum growth on Lowenstein-Jensen medium at 30°C. Laboratory personnel should be notified in advance since AFB cultures mostly are carried at higher temperatures. Cultures should be observed for 6-12 weeks.[5]  A negative acid-fast stain does not rule out a non-tuberculous skin and soft tissue infection. Mycobacterial cultures are necessary to confirm or exclude the diagnosis.[6]  

M marinum is a photochromogen (Runyon group 1), producing a yellow pigment when exposed to light.

M marinum produces urease and catalase (weakly) but does not produce niacin or nitrate.

Polymerase chain reaction (PCR) amplification techniques using Mycobacterium genus-specific primers can be used to diagnose M marinum infection directly in the biopsy sample.

Tuberculin skin test using purified protein derivative is positive in 67% to 100% of cases.[7]

Quantiferon-TB Gold and enzyme-linked immunospot assay may be positive in M marinum infections.[7, 8]

Positive blood culture findings have also been reported in disseminated infections.[9]

The presence of granulomas on histopathology can be suggestive of non-tuberculous mycobacteria but the specificty is poor as many disease processes can cause granulmatous inflammation.[6]

First, obtain radiography of the affected area to evaluate for underlying osteomyelitis.

Obtain either MRI or CT scanning of the affected area if tenosynovitis or deeper infection is suspected, including osteomyelitis if the screening radiography findings are unrevealing. This would also be indicated in patients with prosthetic material from a previous injury.

Surgical drainage of skin lesions often is unnecessary. Deeper-structure infection may require surgical debridement.

Histologic findings often are nonspecific during the first 3 months of infection. An absence of epithelioid and multinuclear cells is not unusual in acute lesions. Younger lesions show epidermal hyperkeratosis, a mixed inflammatory response, or, possibly, frank suppuration. Older lesions may present as organized granuloma. Caseation is uncommon. Granulomatous inflammation is found in 76% of cases.[10]

The organisms are acid-fast and may have a transverse banding pattern. Ziehl-Neelsen staining of the skin tissue specimens is positive in 9% to 13% of localized cases but is more likely to show the organism in disseminated disease.[5]

The mainstay of treatment in M marinum infection is antimicrobial therapy.

In the absence of clinical trial data, current treatment guidelines recommend treatment with 2 antibiotics until 2 months after resolution of symptoms. The treatment duration typically is 3-4 months, longer if deeper structures are involved.{ref 51} The 2007 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) statement recommends treatment with 2 active drugs until 1–2 months with ethambutol and macrolide combinations due to better efficacy and tolerability, and monotherapy can be considered with minimal disease.[11]  

The most commonly used antibiotic is clarithromycin according to several studies, and other alternatives include trimethoprim/sulfamethoxazole, linezolid, and tetracyclines. Routine susceptibility testing may be considered for isolates due to the potential for resistance to tetracyclines and fluroquinolones.[6]

 

Surgical drainage of skin lesions may be unnecessary. Complicated infections with involvement of deeper structures may require surgery.

An infectious disease specialist can establish the diagnosis and suggest management. A dermatologist also can provide expertise.

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.

Recommended concentrations of free chlorine in swimming pool water should be kept between 0.4 and 1 mg/L.[12]

Patients with M marinum infection are treated in an outpatient setting.

Follow-up visits with patients should be scheduled weekly until they begin to respond to therapy and then biweekly until the infection is fully cured.

Continue combination therapy or monotherapy 1-2 months after the infection resolves.

Transfer to other facilities is unnecessary.

Refer patients with M marinum infection to an infectious diseases physician or a dermatologist in an outpatient clinical setting.

M marinum is resistant to the antituberculosis medications isoniazid, pyrazinamide, and para-aminosalicylic acid and shows intermediate sensitivity to streptomycin. Isolates are sensitive to rifampin, rifabutin, ethambutol, clarithromycin, and sulfonamides, including trimethoprim-sulfamethoxazole (TMP-SMX). Intermediate or complete sensitivity has been reported for both doxycycline and minocycline. Fluoroquinolones also show activity against M marinum. Routine susceptibility testing is not recommended and should be reserved for cases of treatment failure.

No comparative trials of treatment regimens for M marinum skin and soft-tissue infections have been performed. The recommended approach is to use a combination of 2 active agents until 1-2 months after resolution of lesions or for a minimum of 6 months. Clarithromycin and ethambutol combination treatment is likely to provide optimal efficacy and tolerability. Rifampin should be added to the treatment regimen when osteomyelitis or other deeper-structure infections are present. Other combinations that also have been used include ethambutol/rifampin, clarithromycin/rifampin, cyclines/clarithromycin, and cyclines/rifampin.

Treatment failure is associated with deeper-structure involvement and is not related to drug therapy. Doxycycline and minocycline monotherapy probably should be used for more superficial soft-tissue infections, as treatment failure has been reported. Resistance to doxycycline and rifampin has been reported.[13] Clarithromycin monotherapy has been used with some success. Azithromycin can be an alternative to clarithromycin in other nontuberculous mycobacterial infections, but its efficacy is unknown in M marinum infection.

A recent case report showed that lenalidomide, a thalidomide derivative used to treat chronic lymphocytic leukemia, rapidly resolved a chronic biopsy-proven M marinum skin infection refractory to conventional treatment. The mechanism is unknown but is likely related to the immunomodulation effect of lenalidomide.[14]

Class Summary

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

Rifampin (Rifadin)

Inhibits bacterial RNA synthesis by binding to DNA-dependent RNA polymerase, blocking RNA transcription. Effective for treating tuberculosis and atypical mycobacterial infections and for eliminating meningococci carriage states. Also useful for prophylaxis of Haemophilus influenzae type b infection. Used in combination with other antibiotics for prophylaxis and to treat staphylococcal infections.

Ethambutol (Myambutol)

Suppresses mycobacteria multiplication by interfering with RNA synthesis. Bacteriostatic against tubercle bacilli.

Class Summary

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

Doxycycline (Vibramycin)

Used to treat infections caused by Rickettsia, Chlamydia, and Mycoplasma. Used for community-acquired pneumonia and other common infections due to susceptible organisms. Has activity against M marinum, M fortuitum, and M chelonae. Inhibits protein synthesis and thus bacterial growth by binding to 30S, and possibly 50S, ribosomal subunits of susceptible bacteria.

Clarithromycin (Biaxin)

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.

Levofloxacin (Levaquin)

For treatment of tuberculosis and some atypical mycobacterial infections in combination with rifampin and other antituberculosis agents.

Azithromycin (Zithromax)

Treats mild-to-moderate microbial infections.

Rifabutin (Mycobutin)

Indicated for the treatment of tuberculosis and several atypical mycobacterial infections. If GI upset occurs, administer dose bid with food.

Minocycline (Dynacin, Minocin)

Effective monotherapy. However, resistant strains of M marinum have been reported. Treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma species.

Sulfamethoxazole and Trimethoprim (Bactrim, Bactrim DS, Septra, Septra DS)

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Several case reports have shown the effectiveness of this drug. Reports indicate that it can help eradicate an organism unresponsive to either antituberculars or tetracyclines.