Mycobacterium Xenopi

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Background

Researchers first described Mycobacterium xenopi in 1959 after isolating it from skin lesions of the South African toad Xenopus laevis.M xenopi, a slow-growing, nontuberculous mycobacterium, is often considered to be a saprophyte or an environmental contaminant. It grows optimally at 45°C (113°F) and has been found, occasionally in large numbers, in hospital hot water supplies at the outlet valves of water heaters.[1, 2] M xenopi colonization occurs from ingestion or inhalation of, or cutaneous exposure to, organisms in water, soil, or airborne particles. Colonization of hospital water systems is associated with infection, disease, and nosocomial isolation.

Pathophysiology

M xenopi has low pathogenicity, and host impairment is required to contract disease from the organism. Most M xenopi infections occur in the lungs, usually in patients with preexisting lung disease or with predisposing conditions (eg, extrapulmonary malignancy, alcoholism, diabetes mellitus, HIV infection). Extrapulmonary and disseminated disease may develop in patients with AIDS or other immunodeficiencies.

For pulmonary disease, inhalation of infected airborne particles is the usual route of infection. For skin and soft tissue infections, direct contact through penetrating injuries and surgical procedures provide the route. Person-to-person transmission of nontuberculous mycobacterial disease has never been documented.

Epidemiology

Frequency

United States

Surveillance data for M xenopi infection are not available because such infection is not a reportable disease. More than 500 cases have been reported, but only approximately 70 cases seem to document true disease.

International

Prevalence is unknown.

Mortality/Morbidity

Subjects with documented M xenopi infections are divided into the following broad categories:

Race

No racial predilection has been identified.

Sex

No predilection for either sex has been demonstrated.

Age

No age predilection has been reported.

History

Infection with M xenopi may result in pulmonary infection, usually in older adults with COPD, in patients who are immunocompromised with disseminated disease, or in patients with extrapulmonary disease involving the lymphatic system, skin, bones, or joints.[3, 4] Onset of symptoms is insidious, and the infection may progress slowly or increase and decrease over the course of months or years.

Presenting symptoms

Presenting symptoms of immunocompromised patients with disseminated disease

Possible presenting symptoms of patients with HIV infection

Physical

Physical findings relate to underlying long-term illness and are not specific for M xenopi infection. More than 95% of patients have abnormal lung findings.

Causes

Predisposing factors include the following:

Sirolimus therapy inhibits interleukin 12–induced proliferation of activated T lymphocytes and may be a risk factor.

Laboratory Studies

Serum electrolyte tests may reveal hyponatremia, most likely due to inappropriate secretion of antidiuretic hormone syndrome.

CBC counts may reveal leukocytosis, leucopenia, anemia, reactive thrombocytosis, or thrombocytopenia, or they may be entirely within reference ranges.

Mycobacterial examination of sputum,[5] blood, urine, bronchoalveolar lavage fluid, and tissue biopsies may reveal M xenopi.

American Thoracic Society criteria are used for diagnosing nontuberculous mycobacterial lung disease in HIV-seropositive or HIV-seronegative patients. Use the following criteria when diagnosing symptomatic patients who have infiltrative, nodular, or cavitary lung disease and those with high-resolution CT scan findings that reveal multifocal bronchiectasis and/or multiple small nodules:

Imaging Studies

Chest radiograph

The classic appearance of M xenopi is cavitary apical pulmonary disease. The cavities have thin walls with little surrounding parenchymal infiltration.

Bronchogenic spread of disease is rare and appears as patchy, irregular, alveolar or interstitial opacities.

Adenopathy and pleural effusions are rare and are not isolated findings.

The nonclassic form develops in about 25% of patients and appears as multiple patchy alveolar, interstitial pneumonitis, or interstitial opacities without defined borders (predominantly in the lower lung fields).

M xenopi may occasionally manifest as a solitary pulmonary nodule, usually in asymptomatic individuals who come to medical attention because of possible malignancy. Surgical resection demonstrates changes without evidence of tumor.

Chest CT scan

This defines the features more precisely by possibly revealing bronchiectasis and 5- to 15-mm nodular opacities.

Positron emission tomography (PET)–CT imaging

This often reveals solitary pulmonary nodules that may mimic carcinoma.

Procedures

Histologic Findings

Necrotizing or non-necrotizing granulomatous inflammation is observed in lung biopsy samples.

Staging

Similar to other nontuberculous mycobacteria

Medical Care

A physician detecting a positive M xenopi culture result must differentiate among colonization, contamination, and true disease.

Surgical Care

Surgery may be curative for patients who present with solitary pulmonary nodules and for those with localized pulmonary disease who fail to respond to, or who relapse after, chemotherapy.

Consultations

Diet

Patients do not require special diets.

Activity

Patients do not require activity restrictions.

Medication Summary

Optimal therapy for M xenopi is not established. Response to therapy varies and does not always correlate with the results of in vitro susceptibility testing. Physicians use combination therapy, with 2-4 drugs prescribed from several months to up to 18 months. M xenopi disease should always be treated with at least 2 active drugs because single-drug therapy increases the probability of acquired resistance.

Clarithromycin (Biaxin)

Clinical Context:  Probably most important drug. To avoid development of resistance, should not be used as monotherapy. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Ethambutol (Myambutol)

Clinical Context:  Probably second most important drug. Diffuses into actively growing mycobacterial cells (eg, tubercle bacilli). Impairs cell metabolism by inhibiting synthesis of one or more metabolites, which in turn causes cell death. No cross-resistance demonstrated. Mycobacterial resistance is frequent with previous therapy. Use in these patients in combination with second-line drugs that have not been administered previously. Administer q24h until permanent bacteriologic conversion and maximal clinical improvement is observed. Absorption is not altered significantly by food.

Rifabutin (Mycobutin)

Clinical Context:  Ansamycin antibiotic derived from rifamycin S. Inhibits DNA-dependent RNA polymerase, preventing chain initiation in susceptible strains of Escherichia coli and Bacillus subtilis but not in mammalian cells. If GI upset, administer dose bid with food.

Streptomycin

Clinical Context:  For treatment of susceptible mycobacterial infections. Use in combination with other antituberculous drugs (eg, isoniazid, ethambutol, rifampin). Total period of treatment for tuberculosis is minimum of 1 y; however, indications for terminating therapy may occur at any time. Recommended when less potentially hazardous therapeutic agents are ineffective or contraindicated.

Rifampin (Rifadin)

Clinical Context:  Probably an important drug for treatment. For use in combination with at least 1 other antituberculous drug. Inhibits DNA-dependent bacteria but not mammalian RNA polymerase. Cross-resistance may occur.

Azithromycin (Zithromax)

Clinical Context:  Similar to clarithromycin but may allow once-per-wk dosing.

Levofloxacin (Levaquin)

Clinical Context:  For treatment of tuberculosis in combination with rifampin and other antituberculosis agents.

Class Summary

Therapy must be comprehensive and cover all likely pathogens in the context of the clinical setting.

Further Inpatient Care

Inpatient care is not necessary unless the patient is severely immunocompromised, has disseminated disease, or requires hospitalization for severity of the illness.

Further Outpatient Care

Monitor the patient monthly for possible adverse effects.

Monitoring includes (but is not limited to) the following:

Inpatient & Outpatient Medications

Use at least 2 medications to avoid acquired resistance.

Intravenous administration may be required with disseminated disease.

Transfer

Consider referring difficult cases to a specialist center.

Consider sending cultures to a reference laboratory to test for susceptibility; however, routine susceptibility testing in a patient who has never been treated is not necessary.

Deterrence/Prevention

Complications

Prognosis

Outcome is favorable. Many people are colonized but asymptomatic.

Author

Mansoor Arif, MD, MBBS, Research Associate, Department of Research, Indus Hospital, Pakistan

Disclosure: Nothing to disclose.

Coauthor(s)

Syed Faisal Mahmood, MBBS, Assistant Professor of Infectious Diseases, Department of Medicine, Aga Khan University Hospital, Pakistan

Disclosure: Nothing to disclose.

Specialty Editors

Wesley W Emmons, MD, FACP, Assistant Professor, Department of Medicine, Thomas Jefferson University; Consulting Staff, Infectious Diseases Section, Department of Internal Medicine, Christiana Care, Newark, DE

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Aaron Glatt, MD, Professor of Clinical Medicine, New York Medical College; President and CEO, Former Chief Medical Officer, Departments of Medicine and Infectious Diseases, St Joseph Hospital (formerly New Island Hospital)

Disclosure: Nothing to disclose.

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Larry I Lutwick, MD, Martin Backer, MD, Sailaja Kolli, MD, and Klaus-Dieter Lessnau, MD, FCCP, to the development and writing of this article.

References

  1. Sebakova H, Kozisek F, Mudra R, Kaustova J, Fiedorova M, Hanslikova D, et al. Incidence of nontuberculous mycobacteria in four hot water systems using various types of disinfection. Can J Microbiol. Nov 2008;54(11):891-8. [View Abstract]
  2. Hussein Z, Landt O, Wirths B, Wellinghausen N. Detection of non-tuberculous mycobacteria in hospital water by culture and molecular methods. Int J Med Microbiol. Apr 2009;299(4):281-90. [View Abstract]
  3. Salmon JH, Direz G, Ziza JM, Desplaces N, Brochot P, Eschard JP. Discitis and sacroiliitis diagnosed 15years after iatrogenic Mycobacterium xenopi inoculation. Joint Bone Spine. Mar 9 2012;[View Abstract]
  4. Portillo ME, Sánchez F, Vicente E, Salvadó M. [Trochanteric bursitis due to Mycobacterium xenopi in a patient with pharmacological immunosuppression]. Enferm Infecc Microbiol Clin. May 2011;29(5):399-401. [View Abstract]
  5. Alvarez-Uria G, Falcó V, Martín-Casabona N, Crespo M, Villar Del Saz S, Curran A, et al. Non-tuberculous mycobacteria in the sputum of HIV-infected patients: infection or colonization?. Int J STD AIDS. Mar 2009;20(3):193-5. [View Abstract]
  6. De Lorenzi D, Solano-Gallego L. Tracheal granuloma because of infection with a novel mycobacterial species in an old FIV-positive cat. J Small Anim Pract. Mar 2009;50(3):143-6. [View Abstract]
  7. Al Jarad N, Demertzis P, Jones DJ, et al. Comparison of characteristics of patients and treatment outcome for pulmonary non-tuberculous mycobacterial infection and pulmonary tuberculosis. Thorax. Feb 1996;51(2):137-9. [View Abstract]
  8. American Thoracic Society. Diagnosis and treatment of disease caused by nontuberculous mycobacteria. This official statement of the American Thoracic Society was approved by the Board of Directors, March 1997. Medical Section of the American Lung Association. Am J Respir Crit Care Med. Aug 1997;156(2 Pt 2):S1-25. [View Abstract]
  9. Andrejak C, Lescure FX, Pukenyte E, et al. Mycobacterium xenopi pulmonary infections: a multicentric retrospective study of 136 cases in north-east France. Thorax. Apr 2009;64(4):291-6. [View Abstract]
  10. Andréjak C, Lescure FX, Pukenyte E, Douadi Y, Yazdanpanah Y, Laurans G, et al. Mycobacterium xenopi pulmonary infections: a multicentric retrospective study of 136 cases in north-east France. Thorax. Apr 2009;64(4):291-6. [View Abstract]
  11. Ausina V, Barrio J, Luquin M, et al. Mycobacterium xenopi infections in the acquired immunodeficiency syndrome. Ann Intern Med. Dec 1 1988;109(11):927-8. [View Abstract]
  12. Banks J, Hunter AM, Campbell IA, et al. Pulmonary infection with mycobacterium xenopi: review of treatment and response. Thorax. May 1984;39(5):376-82. [View Abstract]
  13. Bennett SN, Peterson DE, Johnson DR, et al. Bronchoscopy-associated Mycobacterium xenopi pseudoinfections. Am J Respir Crit Care Med. Jul 1994;150(1):245-50. [View Abstract]
  14. Bishburg E, Zucker MJ, Baran DA, Arroyo LH. Mycobacterium xenopi infection after heart transplantation: an unreported pathogen. Transplant Proc. Nov 2004;36(9):2834-6. [View Abstract]
  15. Chen F, Sethi G, Goldin R, et al. Concurrent granulomatous Pneumocystis carinii and Mycobacterium xenopi pneumonia: an unusual manifestation of HIV immune reconstitution disease. Thorax. Nov 2004;59(11):997-9. [View Abstract]
  16. Costrini AM, Mahler DA, Gross WM, et al. Clinical and roentgenographic features of nosocomial pulmonary disease due to Mycobacterium xenopi. Am Rev Respir Dis. Jan 1981;123(1):104-9. [View Abstract]
  17. David E. Griffith, Timothy Aksamit, Barbara A. Brown-Elliott, Antonino Catanzaro, Charles Daley, Fred Gordin, et al. An Official ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases. Available at http://www.thoracic.org/statements/resources/mtpi/nontuberculous-mycobacterial-diseases.pdf
  18. el-Helou P, Rachlis A, Fong I, et al. Mycobacterium xenopi infection in patients with human immunodeficiency virus infection. Clin Infect Dis. Aug 1997;25(2):206-10. [View Abstract]
  19. El-Solh AA, Nopper J, Abdul-Khoudoud MR, et al. Clinical and radiographic manifestations of uncommon pulmonary nontuberculous mycobacterial disease in AIDS patients. Chest. Jul 1998;114(1):138-45. [View Abstract]
  20. Eng RH, Forrester C, Smith SM, Sobel H. Mycobacterium xenopi infection in a patient with acquired immunodeficiency syndrome. Chest. Jul 1984;86(1):145-7. [View Abstract]
  21. First randomised trial of treatments for pulmonary disease caused by M avium intracellulare, M malmoense, and M xenopi in HIV negative patients: rifampicin, ethambutol and isoniazid versus rifampicin and ethambutol. Thorax. Mar 2001;56(3):167-72. [View Abstract]
  22. Griffith DE, Girard WM, Wallace RJ Jr. Clinical features of pulmonary disease caused by rapidly growing mycobacteria. An analysis of 154 patients. Am Rev Respir Dis. May 1993;147(5):1271-8. [View Abstract]
  23. Hadjiliadis D, Adlakha A, Prakash UB. Rapidly growing mycobacterial lung infection in association with esophageal disorders. Mayo Clin Proc. Jan 1999;74(1):45-51. [View Abstract]
  24. Ibarra MR, Algarabel PA, Marquina C, Arnaudas JI, del Moral A, Pareti L. Magnetic phase diagram and anisotropy of pseudoternary (ErxDy1-x)2Fe14B compounds. Phys Rev B Condens Matter. Apr 1 1989;39(10):7081-7088. [View Abstract]
  25. Jiva TM, Jacoby HM, Weymouth LA, et al. Mycobacterium xenopi: innocent bystander or emerging pathogen?. Clin Infect Dis. Feb 1997;24(2):226-32. [View Abstract]
  26. Koizumi JH, Sommers HM. Mycobacterium xenopi and pulmonary disease. Am J Clin Pathol. Jun 1980;73(6):826-30. [View Abstract]
  27. Kotloff RM. Infection caused by nontuberculous mycobacteria: clinical aspects. Semin Roentgenol. Apr 1993;28(2):131-8. [View Abstract]
  28. Lavy A, Rusu R, Mates A. Mycobacterium xenopi, a potential human pathogen. Isr J Med Sci. Nov 1992;28(11):772-5. [View Abstract]
  29. Maimon N, Brunton J, Chan AK, Marras TK. Fatal pulmonary Mycobacterium xenopi in a patient with rheumatoid arthritis receiving etanercept. Thorax. Aug 2007;62(8):739-40. [View Abstract]
  30. Majoor CJ, Schreurs AJ, Weers-Pothoff G. Mycobacterium xenopi infection in an immunosuppressed patient with Crohn's disease. Thorax. Jul 2004;59(7):631-2. [View Abstract]
  31. Martin-Penagos L, Rodrigo E, Ruiz JC, et al. Lung cavitation due to Mycobacterium xenopi in a renal transplant recipient. Transpl Infect Dis. Jun 2009;11(3):249-52. [View Abstract]
  32. Massachusetts General Hospital. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 17-1989. A 58-year-old man with cavitary lung disease. N Engl J Med. Apr 27 1989;320(17):1130-9. [View Abstract]
  33. Matsui Y, Tamura A, Nagayama N, Akashi S, Araki K, Kimura H, et al. [Review of pulmonary Mycobacterium xenopi infection cases: 11 cases of our own and 18 other cases reported in Japan]. Kekkaku. Aug 2010;85(8):647-53. [View Abstract]
  34. Meybeck A, Fortin C, Abgrall S, et al. Spondylitis due to Mycobacterium xenopi in a human immunodeficiency virus type 1-infected patient: case report and review of the literature. J Clin Microbiol. Mar 2005;43(3):1465-6. [View Abstract]
  35. Miller WC, Perkins MD, Richardson WJ, Sexton DJ. Pott's disease caused by Mycobacterium xenopi: case report and review. Clin Infect Dis. Dec 1994;19(6):1024-8. [View Abstract]
  36. Miller WT, Miller WT. Pulmonary infections with atypical mycobacteria in the normal host. Semin Roentgenol. Apr 1993;28(2):139-49. [View Abstract]
  37. O'Brien RJ, Geiter LJ, Snider DE Jr. The epidemiology of nontuberculous mycobacterial diseases in the United States. Results from a national survey. Am Rev Respir Dis. May 1987;135(5):1007-14. [View Abstract]
  38. Olivier KN, Weber DJ, Lee JH, Handler A, Tudor G, Molina PL, et al. Nontuberculous mycobacteria. II: nested-cohort study of impact on cystic fibrosis lung disease. Am J Respir Crit Care Med. Mar 15 2003;167(6):835-40. [View Abstract]
  39. Olivier KN, Weber DJ, Wallace RJ Jr, Faiz AR, Lee JH, Zhang Y. Nontuberculous mycobacteria. I: multicenter prevalence study in cystic fibrosis. Am J Respir Crit Care Med. Mar 15 2003;167(6):828-34. [View Abstract]
  40. Portaels F. Epidemiology of mycobacterial diseases. Clin Dermatol. May-Jun 1995;13(3):207-22. [View Abstract]
  41. Primm TP, Lucero CA, Falkinham JO 3rd. Health impacts of environmental mycobacteria. Clin Microbiol Rev. Jan 2004;17(1):98-106. [View Abstract]
  42. Schmitt H, Schnitzler N, Riehl J, et al. Successful treatment of pulmonary Mycobacterium xenopi infection in a natural killer cell-deficient patient with clarithromycin, rifabutin, and sparfloxacin. Clin Infect Dis. Jul 1999;29(1):120-4. [View Abstract]
  43. Schwabacher H. A strain of Mycobacterium isolated from skin lesions of a cold-blooded animal, Xenopus laevis, and its relation to atypical acid-fast bacilli occurring in man. J Hyg (Lond). Mar 1959;57(1):57-67. [View Abstract]
  44. Shafer RW, Sierra MF. Mycobacterium xenopi, Mycobacterium fortuitum, Mycobacterium kansasii, and other nontuberculous mycobacteria in an area of endemicity for AIDS. Clin Infect Dis. Jul 1992;15(1):161-2. [View Abstract]
  45. Simor AE, Salit IE, Vellend H. The role of Mycobacterium xenopi in human disease. Am Rev Respir Dis. Mar 1984;129(3):435-8. [View Abstract]
  46. Smith MJ, Citron KM. Clinical review of pulmonary disease caused by Mycobacterium xenopi. Thorax. May 1983;38(5):373-7. [View Abstract]
  47. Sniadack DH, Ostroff SM, Karlix MA, et al. A nosocomial pseudo-outbreak of Mycobacterium xenopi due to a contaminated potable water supply: lessons in prevention. Infect Control Hosp Epidemiol. Nov 1993;14(11):636-41. [View Abstract]
  48. Thaunat O, Morelon E, Stern M, et al. Mycobacterium xenopi pulmonary infection in two renal transplant recipients under sirolimus therapy. Transpl Infect Dis. Dec 2004;6(4):179-82. [View Abstract]
  49. Torkko P, Suomalainen S, Iivanainen E, Suutari M, Tortoli E, Paulin L. Mycobacterium xenopi and related organisms isolated from stream waters in Finland and description of Mycobacterium botniense sp. nov. Int J Syst Evol Microbiol. Jan 2000;50 Pt 1:283-9. [View Abstract]
  50. van Ingen J, Boeree MJ, de Lange WC, Hoefsloot W, Bendien SA, Magis-Escurra C. Mycobacterium xenopi clinical relevance and determinants, the Netherlands. Emerg Infect Dis. Mar 2008;14(3):385-9. [View Abstract]
  51. Varadi RG, Marras TK. Pulmonary Mycobacterium xenopi infection in non-HIV-infected patients: a systematic review. Int J Tuberc Lung Dis. Oct 2009;13(10):1210-8. [View Abstract]
  52. Wang HX, Yue J, Han M, Yang JH, Gao RL, Jing LJ. Nontuberculous mycobacteria: susceptibility pattern and prevalence rate in Shanghai from 2005 to 2008. Chin Med J (Engl). Jan 20 2010;123(2):184-7. [View Abstract]
  53. Witty LA, Tapson VF, Piantadosi CA. Isolation of mycobacteria in patients with pulmonary alveolar proteinosis. Medicine (Baltimore). Mar 1994;73(2):103-9. [View Abstract]
  54. Wolinsky E. Mycobacterial diseases other than tuberculosis. Clin Infect Dis. Jul 1992;15(1):1-10. [View Abstract]
  55. Zurawski CA, Cage GD, Rimland D, Blumberg HM. Pneumonia and bacteremia due to Mycobacterium celatum masquerading as Mycobacterium xenopi in patients with AIDS: an underdiagnosed problem?. Clin Infect Dis. Feb 1997;24(2):140-3. [View Abstract]