Continuing Education Activity

Mycobacterium chelonae is a nontuberculous mycobacterium (NTM), which is classified as rapidly growing mycobacterium (RGM), class IV in the Runyon classification. M. chelonae is ubiquitous in the environment and has been found in soil, water, and aquatic animals. M. chelonae grows optimally at 30-32 C and may have a long incubation period. It is commonly associated with skin and soft tissue infections, especially infections of the extremities (cellulitis, abscessus). This activity reviews infections caused by M Chelonae and highlights the role of the interprofessional team in its management.

Objectives:

• Describe the presentation of M Chelonae infections.
• Review the evaluation of a patient the M. Chelonae infection.
• Summarize the treatment of M. Chelonae infections.
• Explain modalities to improve care coordination among interprofessional team members in order to improve outcomes for patients affected by M. Chelonae.

Introduction

Mycobacterium chelonae is a nontuberculous mycobacterium (NTM), which is classified as rapidly growing mycobacterium (RGM), class IV in the Runyon classification. M. chelonae was first isolated from a turtle in 1903 by Freidmann, who referred to it as "turtle tubercle bacillus. RGMs account for 50% of known mycobacterial species and are divided into six groups, which are as follows: Mycobacterium fortuitum group, M. chelonae/Mycobacterium abscessus complex, Mycobacterium smegmatis, Mycobacterium mucogenicum group, Mycobacterium mageritense/Mycobacterium wolinskyi and the pigmented RGM.

M. chelonae and M. abscessus were considered identical until 1992 when M. chelonae was elevated to species status. Both M. chelonae and M. abscessus have an identical sequence in the 54-510 region but can be differentiated by their intergenic sequence (ITS), hsp65, or gene sequences. Susceptibility profiles can be helpful, but they are not ideal in differentiating between the M. chelonae group and M. abscessus group. M. chelonae group is characterized by high MICs of cefoxitin (> 64 mg/L) and susceptibility to tobramycin (MIC ≤ 4 mg/L), whereas M. abscessus shows lower MICs of cefoxitin (≤ 64 mg/L) and resistance to tobramycin (MIC of > 8 mg/L) (3).

M. chelonae is ubiquitous in the environment and has been found in soil, water, and aquatic animals. M. chelonae grows optimally at 30-32 °C and may have a long incubation period. It is commonly associated with skin and soft tissue infections, especially infections of the extremities (cellulitis, abscessus). M chelonae also causes catheter-related infections and post-surgical infections after implants, transplants, and injections such as sclerotherapy. The eye is second most frequent organ involved. Pulmonary infections are rare when compared to M. abscessus. Invasive infections like bacteremia, osteomyelitis, intraabdominal abscess, and disseminated cutaneous infections are common in immunosuppressed patients such as those on steroids, monoclonal antibodies, and post-transplant immunosuppression. Patients with cancer and or chronic kidney disease are also susceptible to disseminated and invasive disease due to M. chelonae.[1][2][3][4]

Etiology

M. chelonae is a nonmotile, non-spore-forming, gram-positive, acid-fast bacillus. It is a large bacillus with a beaded appearance. M. chelonae is a non-chromogen and classified under group IV of Runyon classification. It is grouped in M. chelonae/M. abscessus group among the six groups of rapidly growing mycobacterium. While rapid growers form colonies in seven days, M. chelonae colonies take longer with a mean incubation period of 15 days and may take up to six to eight weeks. M. chelonae grows best at 30-32° C. Other mycobacterial in the same group as M. chelonae are M. abscessus and its three subspecies. Biochemically, M chelonae are nitrate negative, do not tolerate 5% NaCl, and fail to turn dark brown when grown on ferric ammonium citrate (iron uptake). M. chelonae and M. abscessus can be separated biochemically by the utilization of the citrate (4). M. chelonae is 100% citrate positive unlike M. abscessus, which is 80% citrate negative. M. chelonae is catalase positive and oxidase negative. The biochemical methods are inadequate for clinical use. Currently, molecular techniques are frequently used for the diagnosis of atypical mycobacterial infection.[5][6][7]

M. chelonae is one of the most pathogenic rapidly growing mycobacteria (RGM). In immunocompetent patients, the most common clinical scenario is the localized skin infections, infection after an invasive procedure, or catheter-related infection. Pulmonary infections due to M. chelonae are rare, but colonization is common in cystic fibrosis patients. Disseminated and invasive infections are seen in immunocompromised patients. Person to person transmission has not been documented.Cervical lymphadenitis in children can occur but is rare. Mycobacterium avium intracellulare and Mycobacterium hemophilum are more frequently associated with cervical lymphadenitis in children compared to M chelonae.

Epidemiology

M. chelonae and the other RGM are not reportable infections in the United States, and the true prevalence is unknown. Most Nontuberculous mycobacteria (NTM) shows increased prevalence in the southern states of Florida, Georgia, Louisiana, and Texas. The national survey done between 1981-1983 evaluating NTM prevalence, showed an annual disease prevalence of 1.78 NTM cases per 100,000 persons, with M. chelonae/M. abscessus reported as 0.08 case per 100,000 persons. In a study done in Oregon (2005 to 2006) an annualized prevalence of 7.2 cases per 100,000 persons was reported. In that study, M chelonae prevalence was 0.2 cases per 100,000 persons, with the majority causing skin and soft tissue infections. M. chelonae cases have been reported globally from the Americas, Eurasia, and Australia, and skin and soft tissues infections remain the most frequent. Overall, there is a trend towards increasing NTM infections worldwide. No age, sex or race predilection has been identified. No seasonal trend has been documented in the M. chelonae skin and soft tissue infections. M. chelonae have been found in drinking water systems, as the organism is resistant to chlorine. It has been reported more frequently than M. abscessus but less than M. fortuitum or M. gordanae. M. gordanae is the most frequently reported mycobacteria found in drinking water systems.[8]

History and Physical

Mycobacterial infections including M. chelonae infections can be categorized into several clinical patterns: pulmonary disease, skin and soft tissue infections, musculoskeletal infections, disseminated disease, catheter-associated disease. and lymphadenitis. Skin and soft tissue infections are the most common presentations of M. chelonae infections. Infections occur in both immunocompetent and in immunocompromised hosts. M. chelonae has a predilection to extremities as it has a tendency to grow at a lower temperature. Nodules, papular rash, and sporotrichoid pattern have been reported. Skin lesions due to M. chelonae in the setting of sclerotherapy, acupuncture tattoos, and other injection procedure have been reported. Skin lesions can progress to pustules, hemorrhagic crusts, and abscess formation. M. chelonae can also present with Nodular lymphangitis (sporotrichoid lymphocutaneous infections), which is characterized by the development of suppurative inflammatory nodules along lymphatic vessels on the extremities [8]. Disseminated cutaneous disease and advanced skin lesions are common in immunosuppressed patients. Sweet syndrome can be a presenting feature of M. chelonae infection particularly if the skin lesions are on the extremities. Skin lesions mimicking lupus vasculitis can occur due to M. chelonae infection. Disseminated disease can present with multiple lesions, complex lesions and in more proximal location. Umbilicated papules, pustules involving the face and upper trunk may be present.

• M. chelonae involving the bone, joints, and muscles has been reported and is common in immunosuppressed patients, deep joint injections, or surgical procedures.
• M. chelonae can be a contaminant in endoscopes. Catheter-related infections, presenting as fever, sepsis, or disseminated skin lesions due to M. chelonae have been described in immunocompromised and pregnant patients.

Evaluation

Infection with M. chelonae may be asymptomatic. Colonization of the pulmonary tract in cystic fibrosis patients is likely. M. abscessus frequently cause pulmonary infections. Skin biopsy and cultures should help to evaluate skin and subcutaneous infections on the extremities, those not responding to antibiotics, or in patients who had injection procedures or are immunocompromised. The biochemical evaluation in the microbiologic lab is inadequate to identify NTM to the species level, which is important for instituting appropriate therapy. Molecular techniques such as polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) should be utilized to identify NTM including M chelonae. M. chelonae can have unpredictable resistance pattern. However, most are sensitive to macrolide and aminoglycosides. Susceptibility testing is recommended.

High-performance liquid chromatography (HPLC) alone is not enough to separate M. chelonae from M. abscessus. Acridinium ester-labeled DNA probes specific for M. chelonae have not been approved. DNA analysis of hypervariable regions A and B cannot differentiate isolates of M. chelonae and M. abscessus, although they do vary at other 16S rRNA gene sites (only by a total of 4 bp). PRA method currently has been adopted widely for identification of NTM. This system is based on the coupling of the PCR of a heat shock protein (HSP) followed by restriction fragment length identification, which is species specific. Although sufficient to differentiate M. chelonae from M. abscessus but may not be enough for newer species of NTM.

Treatment / Management

M. chelonae are uniformly resistant to cefoxitin, imipenem is preferred instead. Tobramycin appears to be more active than amikacin. Isolates are susceptible to tobramycin (100%), clarithromycin (100%), linezolid (90%), imipenem (60%), amikacin (50%), clofazimine, doxycycline (25%), and ciprofloxacin (20%). Clarithromycin monotherapy can be sufficient for localized skin infections. However, there are cases of development of resistance during therapy, which occurs due to a single point mutation at position 2058 of 23S rRNA. For lung disease, disseminated disease and invasive disease with bone and soft tissues involvement, atleast six months of therapy is recommended with atleast two drugs, including a macrolide, and a second agent based on susceptibility. Surgical debridement, removal of foreign body, and catheters are an important adjunct to successful therapy. Optimal therapy for lung infection is unknown but most likely similar to other NTM, which results in 12 months of sputum culture negativity. In many published cases of M. chelonae infections in immunosuppressed patients, dual therapy with macrolide and amikacin was successful. Corneal infections should be treated with topical agents as well as systemic agents. Treatment should be based on susceptibilities whenever possible. Eye drops containing macrolides, aminoglycosides, and fluoroquinolones are useful.[9][10][11][12][11]

Differential Diagnosis

• Actinomycosis

• Blastomycosis

• Cryptocosis

• Histoplasmosis

• Mycetoma

• Mycobacterium abscesses

• Mycobacterium kansasii

• Mycobacterium marinum infection

• Mycobacterium xenopi

• Nocardiosis

Enhancing Healthcare Team Outcomes

M. Chelonae can cause infection of almost any organ in the body. The organism is often resistant to many antibiotics and is best managed by an interprofessional team that includes a surgeon, infectious disease specialist, wound care nurse, an internist and an intensivist. Surgical debridement, removal of foreign body, and catheters are an important adjunct to successful therapy. In many cases, the treatment has to be continued for weeks or months. For patients who are immunocompromised, the prognosis is guarded.[13][14]