Nontuberculous mycobacterial skin and soft tissue infections in children

INTRODUCTION — Nontuberculous mycobacteria (NTM) are a miscellaneous collection of acid-fast bacteria that are widespread in the environment [1]. They have been isolated from numerous environmental sources including water, soil, food products, and domestic and wild animals [2]. Health care-associated transmission has occurred with medical equipment [3-5].

This topic will provide an overview of NTM SSTI infections, focusing on immune competent children. Infections caused by Mycobacterium leprae and Mycobacterium ulcerans (Buruli ulcer) and NTM lymphadenitis, pulmonary infections, disseminated infection, and bacteremia in children are discussed separately.

●(See "Leprosy: Epidemiology, microbiology, clinical manifestations, and diagnosis" and "Leprosy: Treatment and prevention".)

●(See "Buruli ulcer (Mycobacterium ulcerans infection)".)

●(See "Nontuberculous mycobacterial lymphadenitis in children".)

●(See "Nontuberculous mycobacterial pulmonary infections in children".)

●(See "Disseminated nontuberculous mycobacterial (NTM) infections and NTM bacteremia in children".)

MICROBIOLOGY — More than 170 species of have been identified, not all of which have been documented to cause disease in humans [6-9].

●Classification – NTM pathogens are classified as rapidly growing or slowly growing (table 1). Rapidly growing species grow within seven days and include Mycobacterium fortuitum, Mycobacterium abscessus, and Mycobacterium chelonae. Slowly growing species require several weeks to grow and include Mycobacterium avium complex (MAC), Mycobacterium marinum, and Mycobacterium kansasii. (See "Microbiology of nontuberculous mycobacteria", section on 'Classification'.)

●Disease associations – NTM can cause a broad range of infections that vary depending on the particular NTM species and the host. In children, NTM cause four main clinical syndromes: lymphadenopathy, skin and soft tissue infection (SSTI), pulmonary disease (predominantly in children with underlying pulmonary conditions), and disseminated disease (predominantly in children with immune compromise).

The most common causes of NTM SSTI include M. fortuitum, M. abscessus, and M. chelonae, which are rapidly growing species, and M. marinum and M. ulcerans, which are slowly growing species [9-16]. Rapidly growing mycobacterial species predominate in NTM SSTIs [17]. They are resistant to commonly used disinfectants (eg, chlorine, formaldehyde, glutaraldehyde, organomercurial compounds) and may grow in nonspecific culture media as well as mycobacterial-specific media [18,19].

The microbiology, culture requirements, and methods of speciation for NTM are discussed separately. (See "Microbiology of nontuberculous mycobacteria".)

EPIDEMIOLOGY — Estimates of the true burden of NTM infections in children are unavailable, in part because NTM infections may be asymptomatic; in addition, because NTM infections are not communicable, reporting of NTM infections is not required in the United States or many other countries [2]. In a national electronic health record database that included >9 million inpatients, the six-year prevalence of NTM SSTI was 4.4 per 100,000, with rapidly growing species predominating in the southern states [20]; 14 percent of cases occurred in children <18 years of age. In statewide surveillance from a single state, the incidence of extrapulmonary NTM infections (not limited to the SSTI) was estimated to be 2 per 100,000 residents per year in children <10 years of age (most of which were lymphadenitis) and 0.1 per 100,000 residents per year in children 10 through 19 years of age [21]. The overall prevalence of NTM disease appears to be increasing with time (possibly as a result of enhanced detection) [14,16,18,22-25]. (See "Epidemiology of nontuberculous mycobacterial infections".)

NTM are transmitted through environmental sources. Water (from both natural and treated sources) is a common reservoir [26-30]. Aquatic transmission of NTM is facilitated by the formation of biofilms, which permit survival under a variety of environmental conditions and, through detachment, allow dissemination of large numbers of organisms [31]. In surveillance from Australia, where reporting of NTM species is mandatory, Mycobacterium haemophilum infections in children increased following episodes of severe flooding [15]. (See "Pathogenesis of nontuberculous mycobacterial infections".)

Skin abrasions and penetrating trauma (including injections, piercing, acupuncture, tattooing, surgical procedures, and gunshot wounds) are the usual portal of entry for NTM SSTI [11,32-44]. The incubation periods are variable [9]. (See "Tattooing in adolescents and young adults", section on 'Localized infection'.)

In outbreaks of cutaneous infection due to rapidly growing mycobacteria (eg, M. abscessus, M. chelonae, M. fortuitum), the incubation period was approximately one month but ranged from 12 to 119 days [34,45-47]. In a review of 40 cases of M. marinum infection, the median incubation period was 21 days (range 5 to 270 days) [48].

CLINICAL FEATURES

General features — NTM SSTI typically occurs in healthy children with cutaneous exposure to NTM. NTM SSTI also occurs in children with immune deficiency and may be an early sign of disseminated NTM disease (picture 1) [49-54]. (See "Disseminated nontuberculous mycobacterial (NTM) infections and NTM bacteremia in children", section on 'Clinical features'.)

NTM SSTI typically follow cutaneous trauma in swimming pools, aquariums, or natural bodies of water [54-56]. The most commonly affected sites are the leg and foot [15]. Cutaneous infection may occur at the site of surgery, vascular catheters, dental instrumentation (eg, pulpotomy), injections, piercing, tattooing, or acupuncture [11,32-38,57].

Cutaneous NTM infections are polymorphous [15,58,59]. Ulcerations (picture 2), plaques, folliculitis, erythematous papules, and nodules (picture 3) have been described [58,60,61]. The variations in clinical presentation may contribute to delays in diagnosis.

NTM skin and soft tissue disease often starts as a slowly growing indurated area that begins to ulcerate after a few weeks. In contrast to pyogenic infections, most NTM lesions are painless (M. haemophilum is the exception), systemic signs of inflammation are absent, and regional lymphadenopathy is uncommon [59].

Rapidly growing NTM — Cutaneous infections with rapidly growing mycobacteria (eg, M. fortuitum, M. abscessus, M. chelonae) may occur following puncture wounds, surgical procedures, dental procedures, open fractures, or water exposure (eg, wading pools, whirlpool footbaths) [41,45,47,62-64]. In outbreaks of SSTI due to rapidly growing mycobacteria, the incubation period was approximately one month, but ranged from 12 to 119 days [34,45-47].

Although there is a wide spectrum of manifestations, SSTI caused by a rapidly growing NTM usually manifest as localized cellulitis, draining abscess, or an individual nodule with minimal tenderness [49,50,65,66]. These infections are clinically indistinguishable from those caused by other bacteria (eg, Pseudomonas aeruginosa, Staphylococcus aureus) [67]. Some case series have noted that M. fortuitum infection usually results in a single cutaneous lesion, while M. chelonae and M. abscessus result in multiple lesions [68].

M. marinum — SSTI due to M. marinum usually follows cutaneous trauma in (or exposure of traumatized skin to) aquariums, swimming pools, or natural bodies of water [54-56,69]. The incubation period is variable; in a review of 40 cases of M. marinum SSTI, the median incubation period was 21 days (range 5 to 270 days) [48].

M. marinum lesions are indolent and typically affect the elbows, knees, and dorsum of feet and hands [70,71]. Involvement of the regional lymph nodes is uncommon.

There are three predominant presentations of M. marinum SSTI [18,69,70]:

●Solitary papules that progress to shallow ulcers with scar formation; the lesions resolve over three to five weeks, with or without drainage.

●Tenosynovitis with pain with passive extension of the digit(s).

●Nodules that spread cephalad from the site of inoculation (picture 3); this pattern is less common than solitary papules; it may resemble sporotrichosis and other forms of nodular lymphangitis; it generally resolves over several months. (See "Soft tissue infections following water exposure", section on 'Clinical evaluation' and "Lymphangitis", section on 'Nodular lymphangitis'.)

M. ulcerans — The clinical features of M. ulcerans are discussed separately. (See "Buruli ulcer (Mycobacterium ulcerans infection)", section on 'Clinical manifestations'.)

M. leprae — The clinical features of M. leprae are discussed separately. (See "Leprosy: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations and diagnosis'.)

Immune-compromised host — Skin lesions may be the earliest manifestation of disseminated disease in immune-compromised patients (picture 1) [49-54]. Immune-compromised patients may have multiple lesions and more frequent ulceration, abscess formation, or local metastatic disease than immune-competent patients [62,72]. Whereas M. avium complex is the most common pathogen isolated in mycobacterial skin infections in HIV-infected children, a variety of species can cause disease in HIV-seronegative immunocompromised children [53], including patients with anti-interferon gamma autoantibodies [73]. (See "Disseminated nontuberculous mycobacterial (NTM) infections and NTM bacteremia in children", section on 'Clinical features'.)

Complications — Penetration of NTM into deeper tissues can inoculate muscle planes or bone, resulting in chronic pyomyositis, tenosynovitis, and chronic osteomyelitis [59]. This occurs in approximately one-third of cases of M. marinum [71].

Digital tenosynovitis caused by M. marinum is known as "fish tank finger" [74]. The signs and symptoms are similar to those of tenosynovitis at other sites: pain and swelling over the tendon, a catching or snapping sensation with movement of the digit, and pain with passive extension of the finger. (See "Infectious tenosynovitis", section on 'Clinical manifestations'.)

Most cases of NTM osteomyelitis follow direct inoculation of the organism (eg, an open fracture); however, cases have occurred after blunt (nonpenetrating) trauma [75]. The epidemiology, clinical features, and diagnosis of NTM osteomyelitis and treatment of NTM osteomyelitis in adults are discussed separately. (See "Epidemiology, clinical manifestations, and diagnosis of osteomyelitis due to nontuberculous mycobacteria" and "Treatment of osteomyelitis due to nontuberculous mycobacteria in adults".)

HISTOPATHOLOGIC FEATURES — Histopathologic features of NTM SSTI include dermal granulomas (occasionally with suppuration), stellate abscesses, sinus tracts, and acute and chronic inflammation [10,32,76,77]. However, none of these features is pathognomonic. NTM granulomas often demonstrate neutrophilic infiltration [78]; eosinophilic infiltration is uncommon. Acid-fast bacilli (AFB) are seen in a minority of cases (only 3 of 18 specimens in one series) [58]. In a series of seven patients with M. marinum cutaneous infections who had pathologic specimens, one had a positive AFB stain and four had granulomatous inflammation [69].

The predominant histopathologic findings may vary depending upon the host's immune status. In a review of biopsy specimens from 27 patients with NTM SSTI, granulomas were more common in specimens from immune-competent patients (18 specimens), whereas deep infiltrates into the subcutaneous tissue, abscess formation, and a foamy appearance of macrophages were more common in specimens from immune-compromised hosts (10 specimens from 9 patients) [10].

DIAGNOSIS — The diagnosis of NTM SSTI requires isolation of a clinically significant NTM species in culture of biopsy, drainage, or aspirate of fluid from skin nodule, wound, or abscess in a child with compatible clinical findings.

Clinical suspicion — Clinical features that should prompt consideration of NTM in children with SSTI include [77]:

●History of water exposure (eg, swimming pool, aquariums, natural bodies of water, etc)

●History of penetrating injury, surgical procedure, or injection

●Negative routine bacterial cultures (if performed)

●Lack of response to antistaphylococcal/antistreptococcal antibiotics (if administered)

A positive (≥5 mm induration) tuberculin skin test (TST) can support the diagnosis of NTM infection in children without risk factors for Mycobacterium tuberculosis [55,61]. However, a positive TST cannot distinguish between NTM and M. tuberculosis. Nor does a negative (<5 mm induration) TST exclude mycobacterial disease. Interferon gamma release assays, which are typically negative in NTM disease, include antigens for some NTM species, including M. marinum [79,80]. (See 'Differential diagnosis' below and "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis".)

Microbiologic testing — Definitive diagnosis of NTM SSTI is made by isolation of NTM in culture of biopsy, drainage, or aspirate of fluid from a skin nodule, wound, or abscess [49]. Culture is essential to differentiate NTM from M. tuberculosis, determine which species of NTM is causing infection, and perform susceptibility testing. However, positive cultures may represent a true pathogen or a contaminant; given the ubiquity of NTM species in tap water, pseudo-outbreaks from contaminated water supplies have been reported [81].

It is helpful to discuss specimen collection, transport, and culture processing with the microbiology laboratory before sending tissue or fluid to the laboratory if NTM infection is suspected. Some species of NTM (eg, M. haemophilum) have fastidious growth requirements. Microbiologic techniques to maximize the yield of NTM cultures are discussed separately. Given the fastidious growth requirements of some NTM species, multiplex mycobacterial nucleic acid amplification assays can aid in the diagnosis for culture-negative cases [82,83]. (See "Microbiology of nontuberculous mycobacteria".)

Positive acid-fast staining supports the diagnosis of mycobacterial disease and increases the likelihood of that the isolate is clinically significant, but does not distinguish between NTM and M. tuberculosis [11]. The finding of acid-fast bacilli (AFB) in routine bacterial culture also supports the diagnosis of NTM (and is suggestive of a rapidly growing species, such as M. fortuitum, M. abscessus, and M. chelonae) [77].

Species identification — Appropriate antimycobacterial treatment of NTM SSTI requires NTM speciation because different species require different treatments. (See 'Specific therapy' below.)

Rapid methods for identification of NTM species from culture include high-pressure liquid chromatography (HPLC) and polymerase chain reaction (PCR) [49]. HPLC examines the mycolic acid fingerprint patterns that differ among most species or complexes of mycobacteria and can be used to speciate NTM, including rapidly growing mycobacteria [84]. HPLC cannot reliably differentiate between M. abscessus and M. chelonae. The role of PCR in the diagnosis of cutaneous NTM disease is unclear. PCR can differentiate between M. abscessus and M. chelonae and has been used to make the diagnosis of NTM SSTI in a few cases [85]. However, the variety of species causing cutaneous NTM disease and the need for drug susceptibility testing limits the utility of PCR. In addition to allowing for speciation, PCR can be used to rapidly identify mutations (eg, erm) associated with inducible resistance to macrolides, as can be seen in M. abscessus [86].

The identification of M. abscessus, M. chelonae, and M. fortuitum may be facilitated by susceptibility testing for amikacin, cefoxitin, clarithromycin, ciprofloxacin, doxycycline, linezolid, sulfamethoxazole, and tobramycin [49]. (See 'Specific therapy' below.)

Clinical significance — When NTM is isolated from a child with SSTI, the clinical significance of the isolate must be determined. The pathogenicity of the various NTM species varies substantially. The possibility that NTM was isolated as a result of contamination also must be considered because NTM is ubiquitous in the environment [49]. Factors that increase the likelihood that the isolate is clinically significant include recovery from multiple specimens and recovery in large quantities (ie, sufficient to result in AFB-positive smears).

Consultation with a specialist in infectious diseases may be helpful in determining the clinical significance of the isolate.

DIFFERENTIAL DIAGNOSIS — The indolent, chronic, and generally nontender lesions of NTM cutaneous disease can mimic those of a number of other cutaneous disorders. Histopathology and/or microbiology generally are necessary to differentiate between cutaneous NTM and other conditions in the differential diagnosis including [62]:

●Sporotrichosis (picture 4A-B) (see "Clinical features and diagnosis of sporotrichosis", section on 'Nodular lymphangitis')

●Nocardiosis (see "Nocardia infections: Epidemiology, clinical manifestations, and diagnosis", section on 'Skin')

●Cutaneous leishmaniasis (picture 5) (see "Cutaneous leishmaniasis: Clinical manifestations and diagnosis", section on 'Localized cutaneous leishmaniasis')

●M. tuberculosis (picture 6) (see "Cutaneous manifestations of tuberculosis")

In immunocompromised hosts, disseminated fungal disease also must be considered:

●Aspergillosis (see "Epidemiology and clinical manifestations of invasive aspergillosis", section on 'Cutaneous aspergillosis')

●Cryptococcal disease (picture 7) (see "Cryptococcus neoformans infection outside the central nervous system", section on 'Nonmeningeal, nonpulmonary cryptococcosis')

●Histoplasmosis (see "Pathogenesis and clinical manifestations of disseminated histoplasmosis", section on 'Skin involvement')

MANAGEMENT

Overview — Treatment of NTM SSTI in children often requires a combination of surgical and medical therapy [9].

Consultation with a specialist in infectious diseases may be warranted, particularly when rapidly growing NTM (eg, M. fortuitum, M. abscessus, M. chelonae) are isolated. No randomized controlled trials or comparative observational studies have evaluated the efficacy of treatments for NTM SSTI. The treatment recommendations below are based upon case series, in vitro susceptibility testing, and clinical experience [87-93]. Our recommendations are generally consistent with the 2007 American Thoracic Society and the Infectious Diseases Society of America guidelines on the management of NTM diseases and the American Academy of Pediatrics Committee on Infectious Diseases [9,49].

Surgical therapy — Drainage of abscesses and removal of indwelling foreign bodies, such as intravenous catheters, are essential components of treatment [49,54,66,94]. In contrast to other central line-associated infections that can be treated in situ, given the high risk of relapse [95], catheter removal is recommended for NTM infections [96]. In addition, surgical debridement is optimal for serious localized disease (eg, those with tenosynovitis, ulceration, deep soft tissue infections, device-associated SSTI, and SSTI associated with osteomyelitis).

Antimycobacterial therapy

Empiric therapy — We suggest that children with NTM SSTI be treated with antimicrobial therapy rather than observation. In observational studies, spontaneous resolution took as long as 12 months [32,97,98]. Antibiotic therapy may hasten resolution [97].

Pending NTM speciation, we suggest that children with localized, nonulcerated NTM SSTI be treated based upon the likely species causing the disease, with a macrolide (azithromycin or clarithromycin) plus one of the following (table 2):

●Fluoroquinolone (eg, ciprofloxacin), or

●Doxycycline (only for children ≥8 years old given the prolonged treatment duration), or

●Trimethoprim-sulfamethoxazole (TMP-SMX)

However, the initial empiric regimen may vary depending upon host factors, suspected species of NTM, and the severity of cutaneous disease. Inclusion of parenterally administered antimicrobial agent(s) in the empiric regimen may be warranted if the patient is immune-compromised or if M. abscessus/M. chelonae is suspected (on the basis of high-pressure liquid chromatography testing, which cannot differentiate between the two species). Some experts recommend initial parenteral therapy for serious disease (eg, ulceration, deep soft tissue infection, device-associated SSTI, and SSTI associated with osteomyelitis) [9]. The suggested initial therapy for serious NTM cutaneous disease varies according to the suspected species [9]:

●M. fortuitum – Amikacin plus meropenem

●M. abscessus – Azithromycin (or clarithromycin) plus amikacin plus either cefoxitin or meropenem

●M. chelonae – Azithromycin (or clarithromycin) plus tobramycin plus either meropenem or linezolid

Isolates of rapidly growing mycobacteria (M. abscessus, M. chelonae, M. fortuitum) should be tested in vitro against antimicrobials including clarithromycin, amikacin, imipenem, TMP-SMX, cefoxitin, linezolid, doxycycline, and ciprofloxacin, to which they are often susceptible and for which therapeutic response has been described [9,49]. Based on in vitro susceptibility testing, a two-drug regimen that includes a macrolide will provide coverage for the most common causes of NTM SSTI in children (M. fortuitum, M. abscessus, M. chelonae, and M. marinum) [49,87-89,99,100].

Specific therapy — In children with NTM SSTI in whom a particular species has been isolated, we suggest combination therapy with two drugs to which the isolate is susceptible. However, in vitro susceptibility testing does not always correlate with clinical response, and the antimicrobial regimen may need to be changed if the child fails to improve after four to six weeks.

●M. fortuitum – M. fortuitum typically is susceptible to macrolides, amikacin, carbapenems, fluoroquinolones, and TMP-SMX (table 2) [49,87-89,99-102]. In an in vitro study, M. fortuitum isolates were more susceptible to fluoroquinolones than to other classes of antibiotics [102]. Single-agent therapy with a macrolide is not recommended because M. fortuitum has inducible macrolide resistance [103]. (See "Rapidly growing mycobacterial infections: Mycobacteria abscessus, chelonae, and fortuitum", section on 'Susceptibility testing'.)

●M. abscessus – M. abscessus typically is susceptible to macrolides, amikacin, cefoxitin, or a carbapenem (eg, meropenem) (table 2) [88,89,99-101]. Single-agent therapy with a macrolide is not recommended because M. abscessus has inducible macrolide resistance [103]. (See "Rapidly growing mycobacterial infections: Mycobacteria abscessus, chelonae, and fortuitum", section on 'Susceptibility testing'.)

●M. chelonae – M. chelonae typically is susceptible to macrolides, tobramycin, and carbapenems (table 2) [87-89,99-101].

●M. marinum – Susceptibility testing generally is not performed for M. marinum isolates unless the patient fails to improve after several months of treatment [49]. M. marinum typically is susceptible to rifamycins (rifampin and rifabutin), ethambutol, macrolides, and TMP-SMX (table 2) [9,49].

●M. ulcerans – Treatment for M. ulcerans is discussed separately. (See "Buruli ulcer (Mycobacterium ulcerans infection)", section on 'Treatment'.)

●M. leprae – Treatment of M. leprae is discussed separately. (See "Leprosy: Treatment and prevention", section on 'Antimicrobial therapy'.)

Adverse effects — The antimycobacterial agents that are used to treat NTM SSTI often are difficult to tolerate and some have important toxicities. Important adverse effects include (but are not limited to) ototoxicity and nephrotoxicity with amikacin and streptomycin, optic neuropathy with ethambutol, and hepatotoxicity with isoniazid. The adverse effects of the agents used to treat NTM infections are discussed in greater detail separately. (See "Pathogenesis and prevention of aminoglycoside nephrotoxicity and ototoxicity" and "Manifestations of and risk factors for aminoglycoside nephrotoxicity" and "Ethambutol: An overview" and "Azithromycin and clarithromycin", section on 'Adverse reactions' and "Rifamycins (rifampin, rifabutin, rifapentine)" and "Isoniazid: An overview" and "Isoniazid hepatotoxicity" and "Aminoglycosides", section on 'Toxicity'.)

Duration of therapy — Therapy for NTM SSTI in immune-competent children with isolated cutaneous lesions is usually continued for one to two months after symptom resolution (usually for a minimum of 6 to 12 weeks) [53,71].

Response to therapy — The response to therapy for NTM SSTI is monitored clinically. We suggest follow-up visits at approximately monthly intervals to ensure that patients are taking and tolerating their medications and that their skin lesions are improving.

Alternative diagnoses should be considered in patients who have no response to therapy after four to six weeks. At this point, if there is culture-confirmation, it is important to ask about adherence to antimycobacterial therapy and potential for medication malabsorption (eg, vomiting, diarrhea, concurrent administration of other medications that may decrease serum levels of antimycobacterial therapy).

For patients without definitive microbiologic data who are not improving or are worsening after four to six weeks of antimycobacterial therapy, surgical consultation may be warranted for debridement and to obtain specimens for cultures and histopathology.

The addition of treatment with antistreptococcal and antistaphylococcal antibiotics also may be warranted to address the possibility of pyogenic superinfection contributing to worsening. When adding agents to an antimycobacterial regimen, it is important to add two drugs (eg, a quinolone and TMP-SMX) to the failing regimen; adding a single drug may predispose to the development of resistance.

PREVENTION — Recommendations for the prevention of NTM SSTI in children include [49]:

●Avoiding the use of benzalkonium chloride as a skin disinfectant because it allows the growth of mycobacteria [104,105]

●Avoiding alternative medicine practices that involve the injection of unknown or unapproved substances

●In hospitalized patients, avoiding washing or contaminating open wounds with tap water

●Using treated or sterile water for dental procedures rather than tap water

●Prevention of tattoo-related NTM SSTI are discussed separately (see "Tattooing in adolescents and young adults", section on 'Prevention of infection')

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Nontuberculous mycobacteria" and "Society guideline links: Skin and soft tissue infections".)

SUMMARY AND RECOMMENDATIONS

●The most common causes of nontuberculous mycobacterial (NTM) skin and soft tissue infections (SSTI) in children include rapidly growing NTM species (Mycobacterium fortuitum, Mycobacterium abscessus, and Mycobacterium chelonae), Mycobacterium marinum, and Mycobacterium ulcerans. (See 'Microbiology' above.)

●Skin abrasions and penetrating trauma are the usual portals of entry for NTM SSTI. The incubation period is variable but usually is between three and four weeks. (See 'Epidemiology' above.)

●NTM SSTI may occur as an isolated finding in immune-competent children or as part of the clinical spectrum of disseminated disease in immune-compromised patients. NTM SSTI typically follow cutaneous trauma in swimming pools, aquariums, or natural bodies of water. Health care-associated infection may occur at the site of surgery, vascular catheters, or injections. (See 'Clinical features' above.)

●Cutaneous NTM infections are polymorphous. Ulcerations (picture 2), plaques, folliculitis, indurated erythematous papules, and nodules (picture 3) have been described. (See 'Clinical features' above.)

●The diagnosis of NTM SSTI requires isolation of a clinically significant NTM species in culture of biopsy, drainage, or aspirate of fluid from skin nodule, wound, or abscess in a child with compatible clinical findings. Clinical features that should prompt consideration of NTM in a child with SSTI include history of water exposure, penetrating injury, surgical procedure, or injection; negative bacterial cultures (if performed); lack of response to antistaphylococcal/antistreptococcal antibiotics (if administered), and isolation of acid-fast bacilli (AFB) in routine bacterial culture. (See 'Diagnosis' above.)

●Treatment of NTM SSTI may require a combination of surgical and medical therapy. Drainage of abscesses and removal of foreign bodies (if present) are essential components of treatment. In addition, surgical debridement is optimal for serious localized disease. (See 'Surgical therapy' above.)

●We suggest that children with NTM SSTI be treated with antimycobacterial therapy rather than observation (Grade 2C). Spontaneous resolution may take up to 12 months. (See 'Antimycobacterial therapy' above.)

●Pending speciation, we suggest that children with localized, nonulcerated NTM SSTI be treated with a macrolide (azithromycin or clarithromycin) plus one of the following: a fluoroquinolone, doxycycline (only for children ≥8 years given the prolonged treatment duration), or trimethoprim-sulfamethoxazole (table 2) (Grade 2C). Parenterally administered antimicrobial agent(s) (including amikacin, cefoxitin, meropenem) may be warranted for serious disease (eg, ulceration, deep soft tissue infections, device-associated SSTI, and SSTI associated with osteomyelitis), immune-compromised hosts, or if M. abscessus/M. chelonae is suspected. Once the species is identified, we suggest that the child be treated with two drugs to which the isolate is susceptible (Grade 2C). (See 'Empiric therapy' above and 'Specific therapy' above.)

●Therapy is continued for one to two months after symptom resolution (usually for a minimum of 6 to 12 weeks). (See 'Duration of therapy' above.)