Mycobacterium terrae

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Microbiology

Mycobacteria terrae is a complex consisting of Mycobacterium triviale, Mycobacterium nonchromogenicum, and Mycobacterium terrae. It is a member of the Runyon group III, non-pigmented slow-growing mycobacteria and because it has often been presumed to be clinically non-pathogenic, its further speciation has not been worked out.

Epidemiology

Broadly speaking, the epidemiology of this disease coincides with the availability of laboratory testing and reporting. This infection has most often been observed in immunologically intact hosts. Of the patients in whom predisposing conditions or immune status is reported, the most common immunologic deficits predisposing the patient are: diabetes, malignancy and several other miscellaneous disorders such as renal transplant or alcoholism.

Clinical Manifestations

Though it is sometimes felt to be non-pathogenic, Mycobacteria terrae isolates are occasionally identified by the clinical laboratory on multiple separate cultures in the setting of clinical disease. The most common sites of clinical disease associated with multiple isolates in the setting of pathology include: joints, tendons, lung, gastrointestinal tract and genito-urinary tract. Joints or tendons of the upper extremities are the most commonly involved tissues, and most of these patients it has been observed, were exposed to corticosteroids, either by injection (38%) or systemically (16%).

Laboratory Diagnosis

The laboratory diagnosis should be sought in the setting of non-healing lesions with negative bacterial cultures. The definitive diagnosis is made using a mycobacterial culture media and biochemical assays. Acid-fast bacilli (AFB) smears of samples taken from the affected tissue is also useful in identifying the organism although not specifically. The best means of identifying this organism for definitive classification has been HPLC (High Pressure Liquid Chromatography) analysis of mycolic acid patterns such that an identification of the species can be ascertained.

Pathogenesis

Mycobacteria terrae infection usually arises clinically and results in pathologic tissue invasion and persistence as a result of an inoculation injury in bone, joint and tendon. Like other mycobacterial infections it may invade the tissues in spite of a T-cell response, and there may be specific as yet unidentified host factors that confer susceptibility to this specific infection.

SUSCEPTIBILITY IN VITRO AND IN VIVO

Single Drug

(Tabular MICs? If tabular MICs are listed, use MIC50, MIC90 and range).

Because of the slow growing nature of M. terrae and the general principles that guide therapy in mycobacterial disease to avoid resistance, single drug therapy is discouraged and is not recommended.

Combination Drugs

Because of the lack of data from in vivo studies and the paucity of information on clinical outcomes where in vitro susceptibility has been established, drug choice is largely based on in vitro susceptibility testing with limited clinical outcomes data associated with the cases. The best analysis of susceptibility was done looking at a series of M. terrae isolates from a 4-year period at the National Jewish Hospital in Denver Colorado. These isolates were definitively identified using conventional biochemical assays and most of the isolates were additionally characterized by HPLC analysis.

ANTIMICROBIAL THERAPY

Drug of Choice

The drug combination of choice for M. terrae infection depends on the tissue involved but most commonly would include all three drugs: azithromycin or clarithromycinAND ethambutol AND rifampin. The possibility of adding an aminoglycoside to the regimen, namely amikacin depends on the urgency of the clinical situation and the risks and benefits in the specific case. Amikacin is usually susceptible in vitro, but the systemic or nephro-toxicity may preclude its inclusion unless it is possible to implant amikacin beads after surgical debridement of the affected tissues. The recommended duration of therapy is for at least 12 months when tissues such as bone and tendons are involved (Table 1).

ADJUNCTIVE THERAPY

Adjunctive therapy using surgery with infections involving the bone, joint and tendons is likely crucial to the overall successful outcome. The debridement or resection of relatively avascular tissue, such as soft tissue sites of the hand and the destroyed lung segments or lobes may be an important adjunct to the multi-drug regimen. The use of aminoglycoside beads (i.e., amikacin) in bone and joint infections to achieve higher local drug concentrations and to minimize systemic toxicity is conceptually attractive, but implementing such treatments is often challenging because of limited tissue spaces involved and wound closure constraints, especially for the tendons of the hand.

VACCINES

Vaccines are not available.

ENDPOINTS FOR MONITORING THERAPY

To monitor therapy in most infections with M. terrae, the clinician can follow the healing of the surgically debrided wounds and the resolution of chronic inflammation or drainage while on anti-mycobacterial therapy. Like other chronic infections, the C-reactive protein (CRP) may be followed to a normal level as therapy progresses; however, the CRP may be normal to begin with and its use is not standardized in this rare infection.

PREVENTION OR INFECTION CONTROL MEASURES

While there are no specific preventive or control measures in place, based on the cases observed, avoidance of inoculation injury appears to be the best deterrent to getting this disease. There is no agent known to be appropriate for prophylaxis of this infection. Nor is there any specific guideline for infection control based on known facts of infectivity of this organism. It appears the organism is not communicable person to person as there is no precedent for this type of transmission of infection and thus precautions even for household contacts beyond the usual universal precautions appear unnecessary.

REFERENCES

1. Carbonara S, Tortoli E, Costa D, Monno L, Fiorentino G, Grimaldi A, Boscia D, Rollo MA, Pastore P, and Angarano G. Disseminated Mycobacterium terrae Infection in a Patient with Advanced Human Immunodeficiency Virus Disease. Clinical Infectious Diseases 2000;30:831–835. [PubMed]

2. Smith DS, Lindholm-Levy P, Huitt GA, Heifets LB, Cook JL. Mycobacterium terrae: Case Reports, Literature Review and In Vitro Susceptibility Testing. Clinical Infectious Diseases 2000;30:444-453.[PubMed]

Table 1. Treatments for M. terrae

	First choice	Alternatives	Comments
Drugs	Azithromycin 500mg PO q day AND Ethambutol 15-20 mg/kg/day PO AND Rifampin 600mg PO q day PLUS or MINUS Amikacin 7.5mg/kg IM or IV q 12h	OR Clarithromycin 250-500 mg PO BID (Max 1g/day) OR Amikacin Beads implanted at the site of surgical debridement	Duration of therapy is for a minimum of 12 months

First choice

Alternatives

Comments

Drugs

Azithromycin 500mg PO q day

AND

Ethambutol 15-20 mg/kg/day PO

AND

Rifampin 600mg PO q day

PLUS or MINUS

Amikacin 7.5mg/kg IM or IV q 12h

OR Clarithromycin 250-500 mg PO