Cutaneous lesions from Mycobacterium abscessus. Courtesy of K. Galil, US Centers for Disease Control and Prevention.
Mycobacterium chelonae is a non-tuberculous mycobacteria (NTM), a group comprised of over 190 organisms and defined as mycobacteria species not categorized within the Mycobacterium tuberculosis complex or as Mycobacterium leprae.[1, 2, 3] [Note: some authors will also exclude Mycobacterium ulcerans from the NTM category owing to its distinct clinical presentation.][4] Traditionally, these organisms were organized into phenotypic groups through the Runyon system of classification, which is based on characteristic colony morphology, growth rate, and pigmentation.[5] This resulted in NTM being broadly categorized into rapid growing mycobacteria (RGM) or slow growing mycobacteria (SGM), based on the presence of growth on solid media either occuring within 7 days, or after 7 days, respectively.[3] Improved molecular diagnostics have led to the identification of a multitude of new species, making the taxonomy of NTM a dynamic field. NTM are typically grouped on the basis of their growth rate (ie, rapid or slow) and then further subcategorized based upon genetic relatedness, most commonly determined by 16s rRNA sequencing, rpoB sequencing (sequencing of a highly conserved subunit of the RNA polymerase), or whole genome sequencing.[5] Based on molecular diagnostics, there are 6 groups or complexes of RGM, which include the Mycobacterium chelonae-abscessus group, M fortuitum group, M smegatis group, M mageritense/M wolinskyi, M mucogenicum group, and the pigmented RGM.[6]
The M chelonae-abscessus group (MC-AG) is comprised of at least 11 species and subspecies, including M chelonae and its subspecies, chelonae, bovis, and gwanakae. The latter 2 are of unclear clinical significance in humans.[4] Other notable pathogenic species in the MC-AG include Mycobacterium abscessus and its subspecies abscessus, bolletti, and massiliense, as well as M immunogenum and Mfranklinii.[4] Prior to 1992, M chelonae and M abscessus were considered to be the same species due to their nearly identical biochemical features.[7] Whereas NTM are felt to be of varying human pathogenicity, M chelonae is one species most often recognized as a human pathogen. M chelonae most commonly causes skin and soft tissue infections – both localized and disseminated, but it also has been implicated as a cause of pulmonary infection.[8] Although typically susceptible to macrolides, which are a common backbone in NTM therapy, the resistance patterns of M chelonae species make treatment quite challenging.[9] Because of these differences in antimicrobial susceptibility patterns between NTM species and the often prolonged treatment duration, it is critical to correctly identify the organism, and to establish that M chelonae truly is causing disease.[8] Ultimately, optimal therapeutic interventions including surgery and appropriate choice and duration of antimicrobial therapy have not been established for M chelonae infections. Treatment continues to be guided by expert consensus.
The pathophysiology of M chelonae is best explained by the evidence that the overwhelming number of M chelonae infections typically are linked to traumatic inoculation from the environment. NTM including M chelonae commonly are found worldwide, and human infections have been reported from most of the industrialized world. Environmental studies have isolated these organisms from soil (30 to 78% of soil samples in the United States), both natural and treated water sources, and in domestic and wild animal populations.[10, 8] Multiple studies have documented the ability of NTM to form and grow in biofilms, leading to growth of RGM in samples from water distribution pipes, faucets, and ice machines, as well as medical equipment cleaned with water from these sources.[11] This prominent feature of their pathophysiology is why potable water supplies are considered important reservoirs for human NTM pathogens, and have been implicated in both community acquired and nosocomial infections.[12, 13] M chelonae in particular is one of the NTM species known to be resistant to multiple sterilizing agents (in part because of biofilm formation) including chlorine and glutaraldehyde, which are commonly used as disinfectants in hospital settings.[14, 5]
When identified in a specimen, NTM isolates can represent colonization, true infection, or pseudoinfection/contamination. TM isolates that are pseudo-infecting or contaminants (ie, isolates without a compatible clinical syndrome) sometimes are linked to pseudo-outbreaks.[15] A pseudo-outbreak is a cluster of pseudoinfections often identified by an increased frequency of NTM isolates in patients without a compatible clinical syndrome.[15] Several studies have identified contamination of automated bronchoscope disinfecting machines as the cause of pseudo-outbreaks of M chelonae.[16, 17] M chelonae causes a wide range of clinical syndromes, most commonly skin and soft tissue infections, and can cause disease in both immunocompetent and immunocompromised hosts. Whereas the most common presentation of NTM infection in general is pulmonary disease, M chelonae is unique in that it rarely is thought to be a causative pathogen in pulmonary disease. In a study examining clinical features of pulmonary disease secondary to RGM in 154 patients, only 1 of the 146 isolates was identified as M chelonae.[18]
Skin and soft tissue infections secondary to M chelonae typically are categorized as localized cellulitis or abscess, or disseminated. Localized disease more commonly occurs in immunocompetent patients, whereas disseminated disease is more common in immunocompromised patients. Trauma, either surgical or nonsurgical injury, causing inoculation either via soil exposure or contaminated water or equipment is a clear explanation for the pathophysiology of M chelonae infection[6] in the immunocompetent host. Traumatic inoculation also can lead to osteomyelitis. Cutaneous NTM infections have been associated with tattoos, and a study published in 2012 in NEJM detailed an outbreak of M chelonae infections secondary to tattoo ink.[19] Sporadic pedicure-associated furunculosis secondary to M chelonae also has been identified in multiple studies.[20] Immunosuppression (particularly corticosteroid use, organ transplantation, and rheumatoid arthritis), is an important risk factor for disseminated disease.[21]
A wide variety of procedures have been implicated as the source of health-care associated M chelonae infections including cosmetic, dermatologic, cardiovascular, orthopedic, and otolaryngologic procedures, among many others. Although rare, interventions involving the injection or placement of foreign material including implantable devices, prosthetic joints, subcutaneous injections, and intravenous catheters have been linked to M chelonae infection.[22, 23] Less commonly identified M chelonae infections include sinusitis, otitis media, ocular infections, and bacteremia. Bacteremia typically is thought to be a catheter-associated infection.[9, 15] Although M abscessus and M fortuitum more commonly are identified in cases of mycobacteremia, a 2021 study identified M chelonae as the pathogen in 6 of 28 episodes of RGM blood stream infections.[24] M chelonae is one of the most frequently isolated in NTM ocular infections, the risk factors for which include trauma, prior surgery, and the presence of ocular biomaterials.[25]
Geographic Distribution
NTM are ubiquitous in the environment. Commonly found in soil and water worldwide, they increasingly are being identified as human pathogens.[8] When examining epidemiology of M chelonae specifically, it is important to take into account that historically, M abscessus and M chelonae were identified as one species and it is therefore possible that M chelonae is under or overrepresented in epidemiology studies. The global epidemiology of pulmonary infection secondary to NTM was reviewed in 2015, and worldwide Mycobacterium avium complex was the most frequently identified cause of NTM-pulmonary disease (PD).[26] Upon review of data from Europe, Central and South America, Asia, Africa, and Australia, M chelonae infrequently is identified as 1 of the top 5 causes of NTM-PD. In Central and South America, only one study identified M chelonae (5.7%) as 1 of the 5 most common organisms to cause NTM-PD.[27] Two other studies from this region identify M abscessus as a common organism, with no mention of M chelonae, and no comment is made with regard to differentiation of these 2 species.[28, 27] Three of 12 European studies (ranging 5-9.4% of cases), and 0 studies from the Middle East, South Asia, and Australia identified M chelonae as a cause of NTM-PD.[27] Interestingly, a study from a single medical center in Taiwan identified MC-AG as the second most frequent cause of 30% of NTM-PD; this was the only study out of East Asia that identified MC-AG. Identification of Mycobacterium species in this study was performed using conventional biochemical testing; hence, the inability to differentiate between the species.[29]
In North America, Mycobacterium avium complex (64-85%) was the most commonly identified organism in all included studies (64-85%), whereas M abscessus/chelonae (3-13%) frequently was identified as the second most common species. Studies from various states and regions of the United States examining prevalence of individual NTM species have been published. In a study performed in Oregon between 2005 and 2006, the authors reported an annualized prevalence of NTM disease of 7.2 cases per 100,000 persons; these predominately were pulmonary cases (5.6 cases per 100,000 persons), followed by skin and soft tissue infections (0.9 cases per 100,000 persons). In this study, M chelonae prevalence was 0.2 case per 100,000 persons, with the majority of cases isolated from skin and soft tissue infection. In Washington State, Ford et al examined geographic variability of NTM species; M chelonae was identified in all regions except the Olympic peninsula over their study period.[30] Although never the most frequently identified organism, M chelonae or MC-AG organisms continue to be identified throughout the United States,[5, 8] with 1 study finding that of 100 M chelonae case isolates, 51% came from either Texas or the southeastern coastal states from Louisiana to Maryland.[21]
Age/Sex/Race
The majority of patients worldwide who are diagnosed with NTM-PD tend to be older (mean age of 54-70 years), and except for in Europe, the majority are female. However, these data are for NTM-PD in general, and no clear age or sexual predilection has been identified for M chelonae infection.[26] No clear racial predilection has been identified for M chelonae infection. This is in contrast to NTM-PD in the United States, in which persons classified as “Asian” were found to have relative prevalence rates approximately twice as high as those categorized as “white.”[26]
Frequency
Prevalence of NTM infections appears to be increasing worldwide.[26] Although it is unclear why prevalence appears to be increasing, several factors have been identified as possibly contributory, including improved diagnostics, increased numbers of immunocompromised hosts, and longer life expectancies.[26] Neither pulmonary nor extrapulmonary infections are considered nationally reportable conditions in the United States. Additionally, as microbiologic isolation does not necessarily indicate true disease, especially when isolated from the respiratory tract, it is difficult to assess true prevalence of NTM disease. There have been several notable extrapulmonary infection outbreaks of M chelonae, including those after laser in-situ keratomileusis (LASIK) as well as from infected tattoo ink.[19, 31] Interestingly, as a result of outbreaks of extrapulmonary NTM infections associated with medical devices, cosmetic procedures, and medical tourism, there has been an increase in the number of jurisdictions in the United States that consider extrapulmonary NTM infections to be reportable conditions.[32]
Mortality/Morbidity
Data on mortality attributable to M chelonae infection are very limited, but it appears to be more common when M chelonae is identified as a cause of NTM-PD than in localized or disseminated skin and soft tissue infections.[33] A study examining RGM infections in patients with cancer found that of 59 patients with a definite/probable pulmonary RGM infection, 14 (24%) secondary to M chelonae, RGM infection contributed to death in 7 patients.[34] For patients in this study having a bloodstream infection, the death of just 1 of 141 patients was felt to be attributable to RGM infection, in this case M chelonae.[34] Finally, disseminated infection in this study was associated with a poor prognosis. Of 22 patients with disseminated infection for whom outcomes were reported, 15 (68%) died, with RGM infection either contributing or felt to be the primary cause of death in 7 of these patients.[34] In patients presenting with severe or disseminated disease, their underlying disease process or immunosuppression that predisposed them to M chelonae infection often caused the mortality, rather than M chelonae itself. Much of the morbidity of M chelonae was due to the often toxic and prolonged courses of antimicrobial therapy necessary to treat these infections.
Prognosis is variable and depends upon the patient's clinical syndrome. In general, if the patient is able to tolerate appropriate antimicrobial therapy and any indicated surgical procedures, the prognosis is good.
Patients with infections secondary to M chelonae can present with a variety of clinical syndromes at sites including skin and soft tissue, bone and joint, and less commonly, pulmonary, ocular, bacteremia, and infection of prosthetic materials.[21]
Skin and soft tissue infections (SSTI) can be localized or disseminated. A case series examining M chelonae isolates from 100 skin, soft tissue, and bone cultures identified the associated clinical disease as disseminated cutaneous infection in 53% of isolates. Thirty-five percent of the isolates were characterized as localized cellulitis, abscess, or osteomyelitis. The final 12% of isolates evaluated in this study were catheter infections.[21] SSTI typically will present as a chronic, non-healing, ulcer or cellulitis. Patients frequently will have had courses of antimicrobials traditionally used for bacterial SSTIs and will have demonstrated either initial mild improvement with relapse of infection after cessation of treatment, or no response to therapy at all. In patients with non-resolving or relapsing SSTI, M chelonae is an important pathogen to consider. Patients with localized SSTI may report a history of superficial cosmetic procedures including recent tattoos, pedicures, or mesotherapy. Those with disseminated cutaneous disease are likely to have a history of chronic immunosuppression, either from long-term corticosteroid use, underlying organ transplantation, or rheumatoid arthritis.[21]
As mentioned, pulmonary disease secondary to M chelonae is much less common. A paper examining chronic lung disease due to RGM found only 1 of 146 isolates identified as M chelonae.[18] Symptoms with M chelonae pulmonary disease are similar to symptoms caused by disease with other NTM: patients often present with chronic cough with or without sputum production, and progressive dyspnea. Systemic symptoms including fever, night sweats, fatigue, and weight loss also can occur with these infections. Patients often have a history of underlying pulmonary disease including chronic obstructive pulmonary disease (COPD), cystic fibrosis, and bronchiectasis.[35]
A variety of other rare clinical syndromes secondary to M chelonae are reported in the literature.[5, 6] Although less common than infections with M abscessus and M fortuitum, it is important to consider M chelonae as a pathogen in patients presenting with wound infections after medical or surgical procedures. In addition to wound infections, instrumentation including placement of intravenous or peritoneal dialysis catheters also can lead to infection with M chelonae.[36]
No physical examination findings are pathognomonic for M chelonae infection, and the presentation of these infections varies widely by clinical syndrome. An abnormal pulmonary exam – diminished breath sounds, rhonchi, or rales – would be expected for NTM pulmonary disease depending on the severity and the extent of the disease, but this is not unique to M chelonae infections. The focus here is on the skin and soft tissue features of M chelonae infection, as this is the most likely clinical scenario where it will be encountered.
NTM SSTI can be fairly nonspecific as these infections may present with cellulitis, abscess, ulcers, nodules, sporotrichoid lesions, and draining sinus tracts, among other presentations.[37] These infections can present as single or multiple lesions, depending on the route of infection and the immune status of the host. M chelonae has been documented to cause multiple lesions more frequently than the single lesions of M fortuitum.[12, 38]
Community-acquired disease
Community acquired SSTI and/or bone disease often isdue to traumatic inoculation of M chelonae from the environment. Classic evidence supporting this includes documentation of outbreaks of M chelonae infections associated with tattoo parlors and with contaminated footbaths at nail salons.[20, 19] What about risk factors or causes of pulmonary disease? A study evaluating the clinical relevance of M chelonae-abscessus infections found that pre-existing pulmonary disease, including COPD, smoking, CF, and non-CF bronchiectasis, was the most common pre-disposing condition for NTM pulmonary disease caused by these organisms.[33] However, a systematic review performed by Lange et al failed to identify risk factors for M chelonae pulmonary disease in the 57 patients evaluated.[39] Immune compromise, especially long-term steroid use, hematologic malignancy, solid organ transplant, and rheumatoid arthritis with its associated immunomodulatory medications place patients at increased risk for development of disseminated disease.[21, 5]
Healthcare-associated disease
A multitude of clinical syndromes secondary to M chelonae have been described following medical or surgical procedures. These infections can result from contaminated surgical equipment or implants, or from environmental sources, most commonly tap water. M chelonae infections have been described after cosmetic procedures including liposuction, botox injections, breast augmentation, and cosmetic facial procedures.[40] Surgical implants including ocular implants and porcine heart valves that were contaminated with M chelonae, with resultant infection, have also been reported.[5, 25] Although uncommon, M chelonae intravenous catheter-related infections have occurred, as has M chelonae peritonitis secondary to peritoneal dialysis catheters.[5]
Although untreated infections can lead to significant morbidity, complications of M chelonae infection typically stem from sequalae of the difficult to eradicate disease process and toxicity from therapy. If extensive or disseminated, SSTI or bone infection with M chelonae can require highly morbid surgical debridement. Pulmonary disease can lead to permanent parenchymal damage. If the infection was found to be associated with implanted foreign material, it nearly always is necessary to removal the foreign body to achieve cure. Rarely, severe lung or disseminated disease can lead to death.
Appropriate antimicrobial therapy for M chelonae infections typically requires at least 2 to 3 antimicrobials, 1 or more of which are typically administered intravenously for at least the first 2 to 6 weeks. Depending on the extent and location of disease, length of therapy can be anywhere from a few months to longer than a year. These prolonged courses of multiple antimicrobials place the patient at risk for developing a multitude of antimicrobial-associated complications including drug reactions, antibiotic associated diarrhea, and development of drug resistant organisms.
Cultures
Initial laboratory work-up for M chelonae requires sending a sample for acid-fast bacillus (AFB) stain and culture. M chelonae and other NTM cannot be distinguished from one another or MTB on AFB smear, but rapid nucleic acid amplification tests are available to identify MTB from an AFB positive smear.[41] Mycobacterial organisms are grown on both solid and liquid media. As a RGM, M chelonae growth typically will appear on culture media within 3 to 5 days; it ideally grows at 28C, but between 28C and 35C, which is lower than most other NTM.[5, 15]
Identification
Historically, identification of RGM including M chelonae was based on phenotypic factors including growth rate, pigmentation, and colony morphology.[5] Phenotypically, the colonies appear smooth, and transparent to cream-colored.[15] There are a variety of biochemical tests such as iron uptake, nitrate reductase activity, and arylsulfatase reaction that also are used to distinguish RGM – for example, M chelonae exhibits strong arylsulfatase activity at 3 days.[5] However, given the time consuming nature and often poor reducibility of these tests, identification of RGM via biochemical methods alone no longer is done.[42] High-performance liquid chromatography (HPLC) of mycobacterial cell wall mycolic acids is a technique used for identification of mycobacterial groups; however, given the inability of HPLC to correctly separate species within RGM groups, it typically is not relied upon as the sole method of identification.[5]
Molecular techniques including DNA probe systems and genetic sequencing are the techniques most commonly used for species level identification of NTM.[42] With rare exception, identification of mycobacterial species can be accomplished with sequencing of the 16S rRNA gene. However, M chelonae and M abscessus differ by only 4 base pairs in 16S rDNA sequencing, and typically cannot be distinguished using 16S gene sequencing alone unless complete 16S rRNA sequence analysis is performed.[5] There are additional rRNA genes that often are sequenced in an effort to identify Mycobacterium species, including rpoB and hsp65, the latter of which can be sequenced to differentiate between M abscessus and M chelonae.[6]
Susceptibility testing
Given the difficulty of performing antimicrobial susceptibility testing (AST) on NTM, it generally is accepted that NTM AST should be performed only for clinically significant isolates.[9] For pulmonary isolates, the accepted criteria for determining a clinically significant isolate were defined by the American Thoracic Society (ATS) and Infectious Disease Society of American (IDSA) joint NTM guidelines. Among NTM species, there is significant variability in antimicrobial susceptibility, and as such if an isolate is felt to be clinically significant, performing AST is critical. M chelonae in particular is one of the most resistant pathogenic RGM.[5]
Susceptibility testing for NTM species is typically performed by broth microdilution, as Agar based tests (including the E-test) have shown inconsistent results.[9, 8] The Clinical and Laboratory Standards Institute (CLSI) recommends for RGM such as M chelonae that a standard panel for AST should include amikacin, cefoxitin, ciprofloxacin, clarithromycin, doxycycline (or minocycline), imipenem, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole. For the M chelonae/M immunogenum complex only, the addition of tobramycin susceptibility is recommended.[43] There are additional antimicrobials that may be tested for, but in the setting of insufficient data to establish MIC breakpoints, these agents are not routinely tested.[43] Gene sequencing also is routinely performed for RGM species to determine the presence or absence of the erm gene, which confers inducible resistance to macrolides. This gene is notably absent in M chelonae, and these organisms are considered 100% susceptible to macrolides,[44] although rapid development of macrolide resistance may occur with macrolide monotherapy.[9] In vitro data suggest that tobramycin is the most active aminoglycoside for M chelonae isolates, and this typically will be the only aminoglycoside reported.[8] M chelonae isolates are considered 100% susceptible to tobramycin. Other general antimicrobial susceptibilities reported for M chelonae include linezolid (54-90% susceptible), imipenem (40-60% susceptible, the most active of the carbapenems), amikacin (50-70% susceptible), doxycycline (25% susceptible), and ciprofloxacin (20% susceptible).[6, 8] Of note, susceptibility testing often is done by a reference laboratory only.
Imaging studies as appropriate for the site of clinical concern should be performed when evaluating a patient with a suspected or confirmed NTM infection. Diagnosis of NTM pulmonary disease requires radiographic findings that are identified as “nodular or cavitary opacities on chest radiograph or a high-resolution computed tomography (CT) scan that shows bronchiectasis and multiple small nodules.”[2] Chest radiographs or CT scans also may be performed to monitor response to therapy, although radiographic response may not always correlate with clinical response.[2] A CT scan or MRI of areas of concern for localized skin and soft tissue or bone infections may be performed to characterize the degree of infection. If there is concern for disseminated infection, a CT of the abdomen and pelvis also may be warranted.
AFB culture, identification, and susceptibility testing are by far the most important tests for diagnosis and treatment of M chelonae infection. In general, clinicians may use laboratory values such as white blood cell count, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP), to help establish the inflammatory state of a patient felt to have a NTM infection. However, these tests are all non-specific and are not required in the evaluation of M chelonae. Skin testing with NTM specific antigens is neither routinely performed nor recommended.
In general, procedures performed for M chelonae fall into 1 of 2 categories – diagnostic or treatment. Diagnostic procedures may include bronchoscopy with bronchial alveolar lavage (BAL) and biopsy of concerning skin lesions. Surgical procedures fall on a spectrum from incision and drainage of cutaneous lesions to surgical lung resection for patients with localized pulmonary disease, which is rare with M chelonae.[9] When pulmonary disease does occur secondary to M chelonae, 20% of patients ultimately will have adjunctive partial pulmonary resection.[39]
Histologic examination of tissue often will show granulomatous inflammation and or acid-fast bacilli (AFB).[2] Hematoxylin and eosin (H&E) staining of biopsy specimens from cutaneous lesions can demonstrate both caseating and non-caseating granulomas and perifollicuitis. Fite stain can be performed to specifically identify AFB.[12]
In general, disease secondary to M chelonae can be considered localized or disseminated. There are no formal staging systems for NTM disease.
There are no guidelines outlining optimal treatment for M chelonae infections, and recommendations are based on expert consensus and experience. Antimicrobial therapy is the mainstay of treatment for M chelonae disease when eradication via surgical intervention cannot be accomplished. It is critical to differentiate M chelonae from the closely related M abscessus when attempting treatment, as therapy for M chelonae has key differences from M abscessus due to fewer antimicrobial resistance patterns.[8] General principles for treatment of disease secondary to M chelonae are similar to treatment of other NTM – therapy typically is prolonged and requires multiple agents that only are chosen after drug susceptibility testing is performed. M chelonae isolates do not contain an erm gene, so they typically are considered fully susceptible to macrolides. This results in macrolides being the backbone of M chelonae therapy.[45]
Although much of the data for M chelonae treatment is with clarithromycin, azithromycin does have some advantages including better tolerability and less severe drug interactions.[46] It is critical to note that macrolide resistance can develop rapidly when monotherapy is used, thus combination therapy is vital.[47] Additional agents typically are aminoglycosides (tobramycin has more in vitro activity against M chelonae than amikacin), linezolid, clofazimine, and occasionally imipenem, fluoroquinolones, and tetracyclines.[8, 45] M chelonae have elevated MICs (>128) to cefoxitin, and are considered uniformly resistant.[5] As therapy recommendations can differ based upon the clinical syndrome, treatment for the most common syndromes is discussed separately.
Pulmonary disease:
Treatment of M chelonae initially was addressed by the ATS/IDSA 2007 treatment guidelines for NTM-PD. Recommendations at that time were to utilize in vitro susceptibilities and to treat with clarithromycin and a second susceptible agent for at least 12 months after negative sputum cultures were obtained.[8] Neither the 2020 updated guidelines nor the 2017 management guideline by the British Thoracic Society cover pulmonary disease caused by M chelonae. In 2022, Lange et al published a statement with consensus management recommendations for less common NTM-PD.[39, 45] Based upon their review of documented cases of M chelonae pulmonary disease, they recommend for mild to moderate disease to start with at least 2 susceptible drugs. For more severe disease, they recommend that 3 drugs should be used, typically with 1 or 2 intravenous drugs for the first 4 to 16 weeks.[45] Given predictable macrolide susceptibility, at least 2 oral drugs, with 1 of those being a macrolide, should be administered for at least 12 months after respiratory cultures convert to culture negative.[45]
Skin, Soft Tissue, and Bone Disease:
Although monotherapy with macrolides (particularly clarithromycin) was considered acceptable, more recent data have shown concern for the development of resistance with macrolide monotherapy.[47, 48] As such, medical treatment of extensive skin and soft tissue infections typically consists of combination therapy (2 to 3 agents) for a minimum of 4 months pending clinical improvement, whereas bone infections require at least 6 months.[8] Similar to pulmonary disease, parenteral therapy typically is continued for the first 2-4 weeks of treatment, which can be followed by oral medications for the duration of therapy.[6] For minor or localized disease, it may be appropriate to treat with only oral medications.[6]
Disseminated disease:
Recommendations for treatment of disseminated disease come from expert consensus based on clinical experience. A parenteral agent in combination with a macrolide in the initial phase of treatment, for a total of 2 to 3 antimicrobials, is recommended, with a duration of at least 6 months.[9] Tobramycin and imipenem (both parenteral) typically are given for the first 2 to 6 weeks in combination with a macrolide.[5]
Surgical resection for pulmonary disease is not well studied in patients with M chelonae, but may be considered in patients who have localized lung disease, fail antimicrobial therapy, or have severe complications such as hemoptysis.[9] A review of documented cases revealed that approximately 20% of patients with M chelonae pulmonary disease required partial pulmonary surgical resection in addition to antimicrobials, typically with a successful treatment course.[45]
It generally is accepted that surgical excision of localized disease can be curative. Surgery may be necessary in the case of abscess formation requiring drainage or with particularly drug resistant organisms.[5, 46] Disseminated skin or soft tissue disease often occurs in patients who are immunosuppressed and unable to control their disease even with antimicrobials, at which point surgical debridement may be necessary.[9] It also is critical to remove any foreign bodies associated with the infection, including catheters, biomaterial associated with ocular surgery, prosthetic joints, and breast implants or other implanted devices.[8, 25]
In general, a consultation with an infectious disease specialist to help guide diagnostic and therapeutic decisions is appropriate. Additional expert guidance can be obtained from several centers around the country including the National Institutes of Health in Bethesda, Maryland; National Jewish Health in Denver, Colorado; and The University of Texas Health Science Center at Tyler in Tyler, Texas – all of which have NTM experts on staff.
There are no specific recommendations for prevention of infection with M chelonae, as these organisms are ubiquitous and community acquired disease has been reported worldwide.[6] Note that M chelonae is not a communicable disease, and no specific isolation precautions are required. Experts have suggested that patients with possible or definite NTM disease be adequately evaluated and treated before initiation of anti-TNF-alpha therapy because of the potential risk for disease progression.[49] Given the known association of M chelonae infection with immunosuppression, it is reasonable to suggest that if an NTM infection is suspected or diagnosed, treatment should be considered before initiation of any immunosuppressive treatments.[21]
Prevention of health-care associated NTM outbreaks and pseudo-outbreaks is addressed in the 2007 ATS/IDSA NTM guidelines. The overarching theme of this guidance is to avoid contact between tap water and invasive devices (intravenous catheters, fiberoptic endoscopes, and surgical instruments), as tap water often can serve as a reservoir for NTM.[8] Additionally, it is critical that any potential health-care associated outbreaks or pseudo-outbreaks are recognized and reported to hospital infection control to prevent further transmission.[8]
The need for long-term monitoring should be determined on a case-by-case basis with evaluation of patient’s clinical syndrome and treatment plan.
If parenteral therapy is to be initiated, patients often will be admitted for the placement of a long-term central venous catheter to facilitate outpatient parenteral antibiotic therapy. There is no specific recommendation for inpatient versus outpatient treatment.
The following are the 3 main guidelines published to help with diagnosis and management of NTM infections:
2007 ATS/IDSA Statement on Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases
This statement addresses the most common clinical manifestations of and treatment for commonly accepted clinically relevant NTM species. It also provides a discussion on basic epidemiology, pathogenesis, and laboratory procedures associated with NTM. This paper specifically addresses M chelonae[8]
2017 British Thoracic Society Guideline for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD)
This guideline addresses the management of NTM-PD caused by the most commonly identified NTM, which does not include M chelonae.[45]
2020 Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline
This guideline focuses primarily on pulmonary disease in adults caused by NTM most commonly identified as pulmonary pathogens. Guidance on M chelonae is not included in this document.[2]
Clinical Context: Clarithromycin inhibits bacterial growth by binding to the 50S ribosomal subunit and inhibiting protein synthesis. It is recommended to treat in combination with other antibiotics. Clarithromycin is frequently used as a component of oral therapy.
Clinical Context: Azithromycin inhibits bacterial growth by binding to the 50S ribosomal subunit and inhibiting protein synthesis. It is recommended to treat in combination with other antibiotics. Azithromycin is frequently used as a component of oral therapy.
Clinical Context: Tobramycin inhibits bacterial growth by binding to the 30S subunit of bacterial ribosomes and inhibiting protein synthesis. Use the patient's ideal body weight for dosage calculation. Tobramycin is used in combination with other antibiotics.
Clinical Context: Amikacin inhibits bacterial growth by binding to the 30S subunit of bacterial ribosomes and inhibiting protein synthesis. Use the patient's ideal body weight for dosage calculation. Amikacin is used in combination with other antibiotics.
Clinical Context: Imipenem/cilastatin combination inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs). Cilastatin prevents renal metabolism of imipenem by competitive inhibition of dehydropeptidase along the brush border of the renal tubules. This combination is used in combination with other antimicrobials.
Clinical Context: Linezolid inhibits bacterial protein synthesis by binding to bacterial 23S ribosomal RNA of the 50S subunit.
Clinical Context: Tigecycline inhibits bacterial protein by binding to the 30S ribosomal subunit. Tigecycline is used in combination with other antibiotics.
Clinical Context: Doxycycline inhibits protein synthesis by binding with the 30S subunit.
Clinical Context: Moxifloxacin inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription. It is used in combination with other antibiotics. Ensure the organism is susceptible.
Clinical Context: Ciprofloxacin inhibits bacterial DNA synthesis by binding to gyrase.
Clinical Context: Ciprofloxacin ophthalmic is used with or without systemic antibiotics (either oral or parenteral). It inhibits bacterial growth by inhibiting DNA gyrase. It is indicated for superficial ocular infections of the conjunctiva or cornea caused by strains susceptible to ciprofloxacin.
Cutaneous lesions from Mycobacterium abscessus. Courtesy of K. Galil, US Centers for Disease Control and Prevention.
