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Mycobacterial (atypical) skin infections
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Atypical or non-tuberculous mycobacterial (NTM) skin infections are being increasingly reported. Mycobacterium marinum and the rapidly growing mycobacteria (RGM), M. abscessus, M. chelonae, and M. fortuitum , are the most common species in the United States. Worldwide, M. ulcerans has the highest prevalence. NTM are ubiquitous in the environment. They exhibit high levels of resistance to disinfectants and have been isolated from sources that may be considered clean, such as chlorinated tap water. Cutaneous infection arises after injury to the skin. Nosocomial infections have been associated with cosmetic and surgical procedures.
Specific Investigations
The diagnosis of atypical mycobacterial skin infections is challenging. Morphology is non-specific and lesions may take months to become apparent. Histopathology is varied and routine bacterial culture conditions are not optimal for growth of mycobacteria.
With clinical suspicion, both mycobacterial tissue culture and histopathology with special stains for AFB are recommended to increase diagnostic yield. Histopathology displays granulomatous and suppurative inflammation with variable pseudoepitheliomatous hyperplasia, ulceration, microabscesses, necrosis, and fibrosis. In immunosuppressed patients, the infiltrate tends to be more diffuse, with increased neutrophils and decreased granulomatous inflammation. Special stains to detect AFB, such as Fite or Ziehl–Neelsen, should be performed, but have low sensitivity (e.g., 34%–51% positive in tissue culture-confirmed cases). AFB are more readily seen with immunosuppression.
Tissue culture submitted specifically for mycobacterial detection is recommended. RGM and M. marinum grow best at 28–30°C, M. ulcerans grows at 25–33°C, and most other slowly growing mycobacteria grow at 35–37°C. Therefore, skin specimens for mycobacteria are typically incubated at both 28–30°C and 35–37°C. Most cultures are incubated for 6 weeks, with growth typically in 2–3 weeks. M. ulcerans may require 8–12 weeks. The AFB smear performed from the specimen prior to culture often has low sensitivity, with one study reporting positive result in 15.1% of specimens ultimately yielding AFB-positive cultures.
Species identification and antimicrobial susceptibility testing are recommended. Evolving molecular techniques allow for rapid and accurate species identification.
An official ATS/IDSA statement: diagnosis, treatment and prevention of nontuberculous mycobacterial diseases
Griffith DE, Aksamit T, Brown-Elliott BA, et al. Am J Respir Crit Care Med 2007; 175(4): 367–416.
These are the most recent US guidelines for NTM infections. It discusses topics pertinent to cutaneous NTM infection, including culture conditions, species identification methods, recommended treatment algorithms, and susceptibility patterns.
Diagnosis of Mycobacterium abscessus/chelonae complex cutaneous infection: correlation of tissue culture and skin biopsy
Sardiña LA, Kaw U, Jour G, et al. J Cutan Pathol 2020; 47: 321–7.
Thirty-three skin biopsy specimens from patients with positive tissue culture were studied. Features included granulomatous inflammation (88%), suppurative inflammation (88%), clear spaces/vacuoles (82%), abscesses/microabscesses (73%), fibrosis (52%), and necrosis (52%). AFB stains were positive in 18 cases (51.5%). Histopathology is affected by the evolutionary stage of the lesion and immunologic status of the host.
The presence of neutrophil microabscesses and epithelioid granulomas should raise the possibility of NTM infection. Additionally, vacuoles within the infiltrate can be a clue.
Mycobacterium Marinum
Cutaneous infection by M. marinum often presents on the arm and may exhibit sporotrichoid spread. The most common sources are aquariums and swimming pools. The infection is frequently limited to skin, but extension to deep structures can lead to tenosynovitis, septic arthritis, or osteomyelitis. Rarely, disseminated infection may occur, especially in the immunocompromised.
Management Strategy
Treatment recommendations are based upon anecdotal success in case series due to the lack of controlled trials. Antibiotic therapy with two or more agents is recommended for 3–4 months, or 1–2 months beyond clinical resolution. Monotherapy can be considered for limited infection. Routine susceptibility testing is not required for M. marinum , except in cases of treatment failure. Isolates are typically susceptible to macrolides, sulfonamides, rifampin, ethambutol, and amikacin, and are susceptible or intermediate in susceptibility to tetracyclines. Treatment failure is usually related to deep structure involvement, rather than a particular antibiotic. Surgical treatment should be reserved for limited disease refractory to antibiotic therapy or in cases of deep structure involvement that require synovectomy or tenosynovectomy due to extensive damage. Second-line treatments have been so designated due to less published experience or due to increased resistance potential (e.g., fluoroquinolones). Third-line treatments are best regarded as adjunctive.
First-Line Therapies
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Epidemiological, clinical, and therapeutic pattern of Mycobacterium marinum infection: a retrospective series of 35 cases from southern France
Eberst E, Dereure O, Guillot B, et al. J Am Acad Dermatol 2012; 66: e15–6.
Success was noted in 34 of 35 (97%) after treatment for 4–24 weeks (mean 12.4 weeks). Monotherapy was successful in 24 patients, including minocycline ( n = 14), doxycycline ( n = 5), and clarithromycin ( n = 5). One patient failed first-line clarithromycin monotherapy. Nine patients were treated successfully with dual antibiotic therapy using clarithromycin in combination with doxycycline ( n = 4), minocycline ( n = 2), rifampicin ( n = 2), or ofloxacin ( n = 1). One patient was successfully treated using a triple combination of clarithromycin, rifabutin, and ethambutol.
This study demonstrated success with monotherapy and clarithromycin-based dual and triple therapy.
Sixty-three cases of Mycobacterium marinum infection. Clinical features, treatment and antibiotic susceptibility of causative isolates
Aubry A, Chosidow O, Caumes E, et al. Arch Intern Med 2002; 162: 1746–5.
Monotherapy was used in 23 patients (37%) and included minocycline ( n = 14), doxycycline ( n = 5), and clarithromycin ( n = 4). Monotherapy use was significantly associated with superficial infection. Forty patients (63%) received at least two antibiotics. Frequent combinations included clarithromycin plus rifampin ( n = 20), doxycycline ( n = 4), or minocycline ( n = 7); and rifampin plus ethambutol ( n = 8), doxycycline ( n = 3), or minocycline ( n = 3). Tetracyclines tended to be prescribed more for superficial infection, while rifampin, rifabutin, and ethambutol were prescribed more for deep infection. Clarithromycin was equally prescribed in superficial and deep infections. Duration of therapy was significantly longer for patients with deep infections (median 7.5 vs. 4 months), and 48% of patients also underwent surgery, which was significantly associated with deep structure infection. Cure was observed for 55 (87%) of patients.
Treatment failure was related to deep structure involvement and not to a particular antibiotic.
Fishing for a diagnosis, the impact of delayed diagnosis on the course of Mycobacterium marinum infection: 21 years of experience at a tertiary care hospital
Castillo NE, Gurram P, Sohail MR, et al. OFID 2020; 7(1): 1–7.
Retrospective review of 46 cases, of which 12 (26%) were complicated by tenosynovitis, septic arthritis, or osteomyelitis. Patients with complicated infection required significantly more surgical procedures. Forty-three patients (93%) were treated with antibiotics. Monotherapy was prescribed in 52.1%, with trimeth- oprim-sulfamethoxazole (TMP-SMX) being the most common, followed by tetracyclines and clarithromycin. Eleven cases (25%) received a two-antibiotic regimen that included macrolides in 91%, in addition to tetracycline, TMP-SMX, rifampin, rifabutin, or ethambutol. The median duration was 4.5 months, and overall was longer in patients with complicated infection . Ninety percent of cases were cured. Clinical outcome was not impacted by number of medications.
The authors recommend avoidance of fluoroquinolones due to resistance. They recommend counseling patients with deep infections about the possibility of multiple surgeries and longer antibiotic treatment duration.
Mycobacterium marinum infection of the hand and wrist
Cheung JP, Fung B, Wong SS, et al. J Orthop Surg 2010; 18: 98–103.
Review article. Due to rifampicin’s excellent bone-penetrating ability, the authors recommend combination therapy with rifampicin plus ethambutol or minocycline for previously untreated patients for 6 months, or at least 2 months beyond clinical improvement. For relapse, they recommend triple therapy with clarithromycin, minocycline, and ethambutol. They advocate surgical excision/debridement for deep structure infections.
Second-Line Therapies
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Successful treatment of refractory cutaneous infection caused by Mycobacterium marinum with a combined regimen containing amikacin
Huang Y, Xu X, Liu Y, et al. Clin Interv Aging 2012; 7: 533–8.
A rapidly progressive infection refractory to rifampicin, clarithromycin, and moxifloxacin responded promptly upon addition of amikacin and discontinuation of moxifloxacin. Complete resolution occurred after treatment with rifampicin, clarithromycin, and amikacin for 6 months.
Treatment of Mycobacterium marinum cutaneous infections
Rallis E, Koumantaki-Mathioudaki E. Expert Opin Pharmacother 2007; 8: 2965–78.
Surgical treatment may not be necessary or may even be contraindicated in some patients. Surgery can be considered for cases with isolated superficial lesions non-responsive to systemic therapy, and in cases that require synovectomy or tenosynovectomy due to extensive damage of underlying tissues. Cryotherapy, electrodesiccation, photodynamic therapy, and local hyperthermic therapy have been reported with some success.
Local hyperthermia therapy for refractory cutaneous Mycobacterium marinum infection
Lee C, Lee JY. Dermatologic Therapy 2017; 30: 1–2.
Case of refractory infection successfully treated with adjunctive local heat therapy. Disposable chemical warm packets (40°C) were applied to skin lesions 5 hours daily for 3 months. Antibiotics were continued during heat therapy.
Mycobacterium marinum infection cured by photodynamic therapy
Wiegell SR, Kongshoj B, Wulf HC. Arch Dermatol 2006; 142: 1241–2.
A patient intolerant of antibiotics was treated successfully with photodynamic therapy once weekly for 3 weeks. Methyl-aminolevulinate was applied for 3 hours, followed by illumination with 37 J/cm 2 of red light.
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