Mycobacterium marinum is a non-tuberculous mycobacterium first isolated from tubercles obtained at necropsy of dead saltwater fish in an aquarium in Philadelphia in 1926. It causes a tuberculosis-like illness in fish. In humans, when injured skin is exposed to an aqueous environment contaminated with M. marinum, infection occurs. This infection presents as a nodular granulomatous disease, which can spread along lymphatics similar to a sporothrix infection. M. marinum is found in plants, soil, and fish. The infections are usually limited to skin and soft tissues and occur in immunocompetent patients. Disseminated M. marinum infection in HIV/AIDS patients have infrequently been reported.
M. marinum is a non-motile, non-spore forming, gram-positive, acid-fast bacillus. M. marinum is slow growing mycobacteria, belonging to group 1 of the Runyon classification. It is a photochromogen and produces a yellow pigment when exposed to light. M. marinum grows best on Lowenstein-Jensen medium at 32 degrees Centigrade (C). Unlike Mycobacterium tuberculosis (MTB), the growth of M. marinum is inhibited at 37 degrees C. Phylogenetically, M. marinum is very closely related to M. ulcerans, and both are closely related to M. tuberculosis based on their 99.3%, 16SrRNA sequence homology. In fact, M. marinum causes tuberculosis-like disease in fish and frogs. Like MTB, M. marinum can survive inside host cells and is proposed as a model to study MTB. Like in MTB infection, M. marinum may cause a positive tuberculin test. M marinum has one rRNA operon per genome, which dictates the pace of mRNA-protein synthesis. Genomic analysis suggests that the rRNA operon is similar in both MTB and M. marinum. Unlike MTB, M. marinum is a rapid grower, so the reason for this difference is unknown. At the infection site, M. marinum has a generation time of 24 hours, similar to MTB, but in the laboratory, at 32 degrees C the generation time is 4 hours. MTB generation time in the lab is 24 hours when grown at 37 degrees C. There is no one good antibiotic regimen for M. marinum.
The first human case of M. marinum was reported from Sweden in 1951 by Norden and Linell. The mycobacteria were isolated from skin lesions of swimmers who had bathed in a contaminated pool. Nowadays, chlorination to sanitize swimming pools is a routine practice; therefore, swimming is no longer a risk factor for M. marinum infection. Potential risk factors are working in wet fields, participating in aquatic sports or cleaning a fish aquarium at home. The annual incidence of M. marinum infection in the USA is 0.27 cases per 100.000 inhabitants. The two conditions required for M. marinum infection are a presence of injury or abrasion to the skin and exposure to contaminated aqueous environment. In one study almost half (49%) of M. marinum infections were aquarium related, 27% were related to fish or shellfish injuries, and 9% were related to injuries associated with salt water or brackish water. Risk factors for HIV-infected individuals are similar exposure. Disseminated infection can occur in immunocompromised patients.
Patient evaluation should identify the likely exposure of the injured skin to aqueous material contaminated with M. marinum. Skin injury may be in the form of minor abrasions, cuts, or major trauma. Besides the aqueous environment, M. marinum is also found in plants and soil. The most common clinical infections due to M. marinum are skin and soft tissue infections most likely due to its propensity to flourish in the cooler environment. A skin infection may present as a solitary, violaceous or red, and plaque or nodule. The nodular surface can be crusted or verrucous. The nodule may appear inflammatory and may have pus. There can be lymphangitic spread in the sporotrichoid presentation. M. marinum should be in the differential diagnosis of poorly healing nodular lesions not responding to antibiotics in the upper extremities. Based upon the exposure to M. marinum, skin lesions can also be present in the lower extremities. M. marinum infections in HIV patients have been reported in the pre-anti-retroviral therapy (ART) era but are uncommon in the post-ART era. Disseminated infection occurs in non-HIV immunocompromised hosts as well.
The laboratory should be notified that M. marinum is suspected, so Lowenstein-Jensen agar cultures can be incubated at 28 to 32 degrees C, in addition to incubating at 37 degrees C. Cultures should be left for six weeks. The positivity rate of cultures ranges from 70% to 80%. Lesions have very low concentration of microorganisms, hence cultures should be obtained even in the absence of microscopic evidence of bacilli. Typical tuberculoid granulomas are seen only in two-thirds of the cases, and the histopathology of nodules can be confused with rheumatoid nodules. One in five nodules may not appear to be of infectious origin in histology. Samples from the deeper parts of the nodule or skin or synovial biopsy may provide information at times, and repeating biopsy can be helpful. M. marinum infections can mimic other histopathological patterns such as a sarcoid-like granuloma or granuloma annulare.
Polymerase chain reaction (PCR) amplification techniques using Mycobacterium genus-specific primers can be used to diagnose M. marinum infection directly in the biopsy sample. Ziehl-Neelson stain of biopsy specimens or yellowish discharge is only rarely positive since the number of mycobacteria in clinical specimens is low.
M. marinum infection can also be an opportunistic infection in patients treated with anti-tumor necrosis factor (TNF)-alpha and other biological drugs. Therefore underlying immunosuppressed state must be excluded upon the diagnosis of M. marinum infection. Tuberculin skin test using purified protein derivative is positive in 67%-100% of cases. Quantiferon-TB Gold and enzyme-linked immunospot assay may also be positive in M. marinum infections but are unhelpful for diagnosis. Positive blood culture findings have also been reported in disseminated infections. Recently in vivo imaging to monitor long-term anti-mycobacterial therapy has been proposed and such diagnostic tools are being developed.
Routine susceptibility testing is not recommended when treating M. marinum infections. There is not much correlation between in vitro susceptibilities and clinical response. The therapy is not standardized. Rifampin is the most active drug against M. marinum with MIC90 of < 0.5mg/mL. In one study, the MIC for ethambutol was 2 to 4.0 mg/mL, for doxycycline was 16.0mg/mL, for imipenem was 8.0mg/mL, and for INH was 8.0mg/mL. M. marinum is intrinsically resistant to pyrazinamide. M. marinum has moderately high MIC90 for ciprofloxacin and levofloxacin but is susceptible to moxifloxacin (MIC90 of 1-2 mg/ml). Linezolid has activity against M. marinum. Clinically clarithromycin-based regimens have had a good success rate irrespective of the in vitro MIC values.
There is no consensus on the regimen or the duration of therapy in M. marinum infections. A spectrum of antibiotic regimens has been used in published cases or case series. There are no randomized controlled trials. Minocycline monotherapy in immunocompetent patients has been used. Combination therapy for immunosuppressed patients has been used. Consider treatment with a chosen regimen for three months prior to changing the antibiotic therapy as the response to therapy is slow. Surgical debridement is often needed. Effective antibiotic therapy is usually associated with healing of all skin lesions within one month of commencing therapy. After that, immunocompetent patients should continue the medications for two more months. Patients who are immunocompromised will need to be treated with two agents for at least six months. In one report, an AIDS patient was successfully treated with rifampin and ethambutol for six months. The lesion recurred after stopping therapy, so therapy was restarted with clarithromycin regimen. Sometimes chronic lifelong suppressive therapy may be needed.
Therefore, it seems prudent to treat immunocompromised hosts with M. marinum infection with two agents, including clarithromycin. The optimal duration of therapy in the setting of the immunocompromised host is unknown. Most experts would treat for six months and possibly lifelong in cases of the persistent immunocompromised state. The disseminated disease was treated for the duration of one year in published case reports. Rifampin and ethambutol were frequently used in invasive M. marinum infections. In a study of 61 clinical isolates, rifamycins and clarithromycin were the most potent against M. marinum.
Surgical debridement is frequently necessary and should be included in the management plan. Antibiotic therapy is needed as well, after surgical debridement.
Mycobacterium marinum infections are on the rise as more people take to water activities. The infection is not easy to diagnose and its managment can be difficult. The infection predominantly affects the extremities and is best managed by a multidisciplinary team that includes a surgeon, infectious disease expert, emergency department physician, wound care nurse and a pharmacist. The lesions are initially treated with antibiotics but resistance is high. Some lesions may require surgical debridement. The wounds are often left open and need daily dressings. The antibiotic treatment is often for weeks or months. The morbidity in immunocompromised individuals is high.
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