Bacterial Classification

M. abscessus was first isolated from a knee abscess in 1952 (1). M. abscessus and M. chelonae were originally considered to belong to the same species (“M. chelonei” or “M. chelonae”), but in 1992, M. abscessus was reclassified as an individual species (1). After M. abscessus was recognized as an independent species, new subspecies, including M. massiliense and M. bolletii, were discovered. Debate has ensued over whether M. massiliense and M. bolletii should be reunited to form one subspecies, M. abscessus subsp. bolletii (6). It is hoped that the debate will be settled as a result of findings from several recent studies that clearly demonstrated, by genome comparison, that M. abscessus complex comprises 3 entities: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii (7–11). Serial changes in the taxonomic classification and nomenclature of M. abscessus complex, from 1992 to 2013, are shown in Figure 1.

M. abscessus subsp. bolletii is recognized as a rare pathogen with a functional inducible erythromycin ribosome methyltransferase (erm) (41) gene. In most M. abscessus subsp. abscessus mycobacterium, this gene leads to macrolide resistance. M. abscessus subsp. massiliense has been proposed to have a nonfunctional erm(41) gene, leading to macrolide susceptibility and a favorable treatment outcome for infections (7–11).

Laboratory Identification

Definitive diagnosis of M. abscessus complex infection in humans is invariably determined by the isolation of M. abscessus complex from clinical specimens. The correct subspecies identification of M. abscessus complex has traditionally relied on phenotypic methods (e.g., biochemical testing for the utilization of citrate) to distinguish them from closely related species like M. chelonae (1). However, this method is not accurate enough to differentiate between the 2 main subspecies of the complex. Instead, rpoB gene–based sequencing is a more reliable method for correctly identifying M. abscessus complex to the subspecies level (10). However, because of the limited differences between the subspecies of M. abscessus complex, some researchers have questioned the accuracy of identification results from the sequencing of a single gene, especially the rpoB gene (10). Many schemes have been used in an attempt to accurately differentiate between subspecies, such as multilocus gene sequence typing, sequencing of the erm gene, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (Figure 2) (10,12). Nonetheless, because the taxonomic classification is still changing, the debate over the optimal identification method will probably also continue.

Respiratory Tract Infections

M. abscessus complex can cause pulmonary disease, especially in vulnerable hosts with underlying structural lung disease, such as cystic fibrosis, bronchiectasis, and prior tuberculosis (2). M. abscessus complex pulmonary disease usually follows an indolent, but progressive, course, causing persistent symptoms, decline of pulmonary function, and impaired quality of life; however, the disease can also follow a fulminant course with acute respiratory failure (2,14). Establishing a diagnosis of pulmonary disease due to M. abscessus complex is not straightforward because isolation of M. abscessus complex from respiratory samples is not, in and of itself, diagnostic of pulmonary disease (2). According to guidelines published by the American Thoracic Society/Infectious Diseases Society of America in 2007, the diagnosis of M. abscessus complex pulmonary disease requires the fulfillment of clinical and microbiological criteria, such as the presence of clinical symptoms; radiographic evidence of lesions compatible with NTM pulmonary disease; appropriate exclusion of other diseases; and, in most circumstances, positive culture results from at least 2 separate expectorated sputum samples (2). Common radiographic findings of M. abscessus complex pulmonary infection (i.e., bronchiolitis; bronchiectasis; nodules; consolidation; and, less frequently, cavities) are shown in Figure 3 (2).

M. abscessus complex is especially prevalent in respiratory specimens from patients with cystic fibrosis (7,15). Recent studies have shown that M. abscessus complex infection is no longer a contraindication for lung transplantation, although postoperative complications and a prolonged treatment course can be expected (7).

Pulmonary disease caused by M. abscessus complex is notoriously difficult to treat. Although there is no standard treatment, current guidelines suggest the administration of macrolide-based therapy in combination with intravenously administered antimicrobial agents; however, this regimen has been shown to have a substantial cytotoxic effect (2). Of 65 patients with pulmonary disease due to M. abscessus complex who received an initial 4-week course of intravenous antimicrobial agents followed by macrolide-based combination therapy, 38 (58%) had M. abscessus–negative sputum samples >12 months after treatment (16). Surgical resection of localized disease in addition to antimicrobial therapy has been shown to elicit a longer microbiologic response than antimicrobial agents alone: sputum samples were M. abscessus complex–negative for at least 1 year in 57% versus 28% of these treatment groups, respectively (17). According to the 2007 American Thoracic Society/Infectious Diseases Society of America guidelines, the treatment options remain limited with current antimicrobial agents, and M. abscessus complex pulmonary disease is still considered a chronic incurable disease (2).

The advancement of subspecies differentiation has allowed for more effective management of pulmonary disease caused by M. abscessus complex. For example, unlike M. abscessus subsp. abscessus, M. abscessus subsp. massiliense does not have inducible resistance to clarithromycin (7). Therefore, knowing that a patient’s infection is due to M. abscessus subsp. massiliense rather than 1 of the other 2 subspecies enables the physician to confidently administer clarithromycin (7,18). In a large study on treatment outcome in patients with pulmonary disease caused by M. Abscessus subsp. massiliense or M. abscessus subsp. abscessus, all patients had similar clinical signs, radiographic findings, and treatment regimens (18). However, after treatment, the percentage of patients who had negative sputum culture results was much higher in the M. abscessus subsp. massiliense–infected group (88%) than in the M. abscessus subsp. abscessus–infected group (25%) (18). The lack of efficacy of clarithromycin-containing antimicrobial therapy against M. abscessus subsp. abscessus isolates in the study could be explained by the subspecies’ inducible resistance to clarithromycin. The study clearly demonstrated how M. abscessus subsp. massiliense and M. abscessus subsp. abscessus have different susceptibility profiles to combination therapy containing clarithromycin and different outcomes from such treatment (18).

SSTIs

SSTIs are also commonly caused by M. abscessus complex; infections range from deep tissue infections to localized skin infections. The 2 major mechanisms for acquiring an M. abscessus complex–associated SSTI are by 1) direct contact with contaminated material or water through traumatic injury, surgical wound, or environmental exposure and 2) secondary involvement of skin and soft tissue during disseminated disease (19). SSTIs caused by M. abscessus complex have been reported in patients who recently underwent cosmetic procedures (e.g., mesotherapy), tattooing, and acupuncture (19). M. abscessus complex SSTIs can also develop after exposure to environmental sources, such as spas and hot springs (19,20). More often, however, these SSTIs develop among hospitalized postsurgical patients, in whom surgical wound infections are most commonly due to M. abscessus subsp. massiliense (21,22). Disseminated M. abscessus complex infections with skin and soft tissue involvement also commonly occur (23). Of note, however, the presence of M. abscessus complex SSTIs can result in or from disseminated M. abscessus complex infections (23). M. abscessus complex skin infection have diverse presentations, including cutaneous nodules (usually tender), erythematous papules/pustules, and papular eruptions or abscesses (Figure 4) (19).

Central Nervous System Infections

Central nervous system (CNS) infections caused by M. abscessus complex are rare, but when they do occur, meningitis and cerebral abscesses are the most common manifestations (Figure 5). Although MAC is responsible for most NTM CNS infections, especially in HIV-infected hosts, M. abscessus complex has increasingly been reported to cause CNS infections in HIV-negative patients (21). In one study, M. abscessus was responsible for most NTM CNS infections in HIV-seronegative patients (8/11 patients), especially in patients who had undergone neurosurgical procedures, patients who had intracranial catheters, and patients with otologic diseases. Treatment outcome depended on the patient’s underlying disease and health status. Clarithromycin-based combination therapy for at least 1 year plus surgical intervention, if needed, offered the best chance for cure (21).

Disseminated Diseases and Bacteremia

Disseminated M. abscessus complex infections, such as lymphadenopathy, SSTIs, pulmonary infections, and bacteremia, are on the rise (23), and bacteremia caused by M. abscessus complex is most often associated with catheter use (24,25). A recent study showed that surgical wound infection may be the portal of entry, especially for M. abscessus subsp. massiliense (26). Optimal treatment modalities include removal of intravascular catheters, surgical debridement, and administration of intravenous antimicrobial agents chosen on the basis of drug susceptibility test results.

Disseminated M. abscessus complex infections tend to occur in immunocompromised hosts, including persons with HIV. However, these infections can also occur in HIV-negative patients. Browne et al. (23) recently showed that neutralizing anti–interferon-γ autoantibodies were present in 81% of HIV-negative patients with disseminated NTM-associated infections, and in adults, these antibodies were associated with adult-onset immunodeficiency similar to that seen in advanced HIV infection. This adult-onset immunodeficiency status can lead to disseminated NTM disease that mimics advanced HIV infection (23).

Ocular Infections

The incidence of NTM ocular infections (keratitis, endophthalmitis, scleritis, and other tissues of the ocular area) has increased over the past decade, and the increase has been attributed to the M. chelonae/abscessus group (27). Interpreting the real trend in ocular infections caused by M. abscessus complex is difficult because most studies have not used reliable tests to differentiate between M. abscessus complex and M. chelonae (27).

Initial treatment of M. abscessus complex ocular infections involves the discontinuation of topical corticosteroids, if used. The optimal treatment strategy (topical therapy, systemic antimicrobial agents, and surgical intervention) depends on the site of the ocular infection (28). Topical therapy, particularly topical amikacin and clarithromycin, can be used to treat some M. abscessus complex ocular infections (e.g., conjunctivitis, scleritis, keratitis, endophthalmitis) (28), and systemic antimicrobial agents can be used for all ocular infections (28). Surgical debridement, including removal of infected tissue, should be considered and is necessary for treatment of infections in some patients (28). Treatment outcome varies according to the site of infection, and early recognition of the infection is crucial.