eMedicine Specialties > Infectious Diseases > Mycobacterial Infections

Mycobacterium Xenopi

Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus
Martin Backer, MD, Fellow in Combined Adult and Pediatric Infectious Diseases, State University of New York Health Sciences Center; Sailaja Kolli, MD, Fellow, Department of Internal Medicine, Division of Pulmonary and Critical Care, The Brooklyn Hospital Center; Klaus-Dieter Lessnau, MD, FCCP, Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Updated: May 12, 2009

Introduction

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.

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:

• The first group comprises young, severely immunocompromised individuals in whom M xenopi infection occurs as an opportunistic infection that may then become disseminated, conferring a high risk of mortality and morbidity.
  • Persons with CD4+ cell counts of less than 50/µL are susceptible hosts for pathogens such as M xenopi.
  • M xenopi can cause 2 patterns of disease in these patients: localized pulmonary disease that can mimic tuberculosis in persons with early-stage HIV infection and disseminated disease in those with advanced AIDS.
• The second group comprises immunocompetent adults with chronic lung disease or chronic obstructive pulmonary disease (COPD) in whom M xenopi infection usually follows a long-term, indolent course.

Race

No racial predilection has been identified.

Sex

No predilection for either sex has been demonstrated.

Age

No age predilection has been reported.

Clinical

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. Onset of symptoms is insidious, and the infection may progress slowly or increase and decrease over the course of months or years.

• Presenting symptoms
  • Chronic productive cough (90%)
  • Dyspnea (80%)
  • Constitutional symptoms such as weakness, malaise, and weight loss (90%)
  • Hemoptysis (20%)
  • Night sweats (20%)
  • Fever (10%)
• Presenting symptoms of immunocompromised patients with disseminated disease
  • Prolonged febrile illness (95%)
  • Wasting syndrome (95%)
• Possible presenting symptoms of patients with HIV infection
  • Advanced disease
  • Low CD4+ cell counts (<50/µL)
  • Prior AIDS-defining illness

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
  • Preexisting lung disease (eg, COPD, bronchiectasis)
  • Pulmonary or extrapulmonary malignancy
  • Alcoholism
  • Diabetes mellitus
  • Immunocompromised state (eg, HIV infection, AIDS)
  • Exposure via inhalation of aerosolized water infected with M xenopi or contact with infected water droplets
  • Sirolimus therapy inhibits interleukin 12–induced proliferation of activated T lymphocytes and may be a risk factor.

Differential Diagnoses

Other Problems to Be Considered

AIDS-related complex
Colonization
Contamination

Workup

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,³ 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:
  • If 3 sputum/bronchial wash results from the previous 12 months are available: Three positive culture findings with negative acid-fast bacilli (AFB) smear results or 2 positive culture findings and 1 positive smear result.
  • If only 1 bronchial wash result is available: Positive culture findings with a 2+, 3+, or 4+ AFB smear result or a 2+, 3+, or 4+ growth on solid media
  • If sputum/bronchial wash results are nondiagnostic or another disease cannot be excluded: Transbronchial or open lung biopsy yielding M xenopi or biopsy showing mycobacterial histopathologic features (granulomatous inflammation⁴ or AFB) and 1 or more sputum or bronchial wash result positive, even in a low number, for M xenopi

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

• Bronchoscopy with bronchoalveolar lavage
• Bronchoscopy with endobronchial or transbronchial biopsies
• Transbronchial needle aspiration
• Video-assisted thoracoscopic biopsy
• Open lung biopsy (rarely indicated)

Histologic Findings

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

Staging

Similar to other nontuberculous mycobacteria

• Presumed colonization
• Localized disease (eg, in the lungs)
• Disseminated disease or mycobacteremia

Treatment

Medical Care

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

• Assess bacteriologic data (eg, repeated isolation, organism identification), clinical symptoms, and radiographic findings within the entire clinical context.
• Treat with chemotherapy, although optimal therapy is not well established.

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

• Infectious disease specialist
• Thoracic surgery specialist
• Pulmonary medicine specialist

Diet

Patients do not require special diets.

Activity

Patients do not require activity restrictions.

Medication

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.

Antibiotics

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

Clarithromycin (Biaxin)

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.

Dosing

Adult

500 mg PO bid

Pediatric

15 mg/kg PO divided bid

Interactions

Toxicity increases with coadministration of fluconazole, astemizole, and pimozide; effects decrease and adverse GI effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, and HMG CoA-reductase inhibitors; serious cardiac arrhythmias may occur with coadministration of cisapride; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increased QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents

Contraindications

Documented hypersensitivity; coadministration of pimozide

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; administer half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies

Ethambutol (Myambutol)

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.

Dosing

Adult

No previous antituberculous therapy: 15 mg/kg/d (7 mg/lb/d) PO; previous antituberculous therapy: 25 mg/kg/d (11 mg/lb/d)

Pediatric

<12 years: Not recommended
>12 years: Administer as in adults

Interactions

Aluminum salts may delay and reduce absorption (administer several h before or after ethambutol dose)

Contraindications

Documented hypersensitivity; optic neuritis (unless clinically indicated)

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Reduce dose in impaired renal function; optic neuritis/color blindness with doses >15 mg/kg/d; obtain ophthalmology consult if 25 mg/kg/d dose used

Rifabutin (Mycobutin)

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.

Dosing

Adult

300 mg PO qd is regular dose; maximum 600 mg/d PO; alternatively, 10-20 mg/kg/d; not to exceed 600 mg/d; if GI upset, administer dose bid with food

Pediatric

Not established; suggested dose, 5 mg/kg/d PO

Interactions

Steady-state zidovudine plasma levels may decrease after repeated rifabutin dosing but do not affect inhibition of HIV by zidovudine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Do not administer to patients with active tuberculosis; no evidence of effectiveness in preventing Mycobacterium tuberculosis infection; may administer isoniazid concurrently in patients requiring prophylaxis against both M tuberculosis and Mycobacterium avium complex; perform hematologic studies periodically in patients receiving prophylaxis because of association with neutropenia and, more rarely, thrombocytopenia

Streptomycin

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.

Dosing

Adult

1 g IM qd
2 times/wk dosing: 15 mg/kg/d IM; not to exceed 1 g/d
3 times/wk dosing: 25-30 mg/kg/d IM; not to exceed 1.5 g/d

Pediatric

2 times/wk dosing: 20-40 mg/kg/d IM; not to exceed 1 g/d
3 times/wk dosing: 25-30 mg/kg/d IM; not to exceed 1.5 g/d

Interactions

Increased toxicity with loop diuretics (eg, furosemide) and amphotericin B; increased prolonged effect depolarizing and nondepolarizing neuromuscular blocking agents

Contraindications

Documented hypersensitivity; non–dialysis-dependent renal insufficiency

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Monthly audiogram; narrow therapeutic index; not intended for long-term therapy; caution in patients with renal failure who are not on dialysis; caution with myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission

Rifampin (Rifadin)

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.

Dosing

Adult

10 mg/kg/d PO/IV; divided doses if patient is intolerant; not to exceed 600 mg/d; treat for 6-9 mo or until 6 mo elapse from conversion to negative sputum culture results

Pediatric

10-20 mg/kg PO/IV; not to exceed 600 mg/d

Interactions

Induces microsomal enzymes, which may decrease effects of acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, oral contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFT findings occur)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Colors urine, sweat, tears, and contact lenses orange-brown; order pretreatment LFT (repeat if symptomatic); obtain CBC counts and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued

Azithromycin (Zithromax)

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

Dosing

Adult

250-500 mg/d PO for 5-14 d
1200 mg/d PO once-per-wk dosage has been used

Pediatric

<6 months: Not established
>6 months: 10 mg/kg PO on day 1, not to exceed 500 mg/d; 5 mg/kg/d PO on days 2-5, not to exceed 250 mg/d

Interactions

May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine

Contraindications

Documented hypersensitivity; hepatic impairment; do not administer with pimozide

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function or prolonged QT intervals; caution in patients who are hospitalized, elderly, or debilitated

Levofloxacin (Levaquin)

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

Dosing

Adult

500-1000 mg/d PO

Pediatric

<18 years: Not recommended
>18 years: Administer as in adults

Interactions

Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 1-2 h ac or pc

Contraindications

Documented hypersensitivity; pregnancy; lactation

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adjust dose in renal function impairment

Follow-up

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:
  • Liver palpation and, if any discomfort, liver function testing
  • Tests for visual acuity and color vision if ethambutol is used
  • Audiometric testing if aminoglycosides are used

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

• To date, no strategy, method, treatment, or therapy prevents M xenopi infection.

Complications

• Chronic wasting syndrome
• Respiratory failure
• Chronic respiratory illness
• Disseminated disease
• Death

Prognosis

• Outcome is favorable. Many people are colonized but asymptomatic.

Patient Education

• Adverse effects of medications
• Patient compliance with medical therapy (risk of acquired resistance if compliance is <80%)

Miscellaneous

Medicolegal Pitfalls

• Overtreatment (of patients without true disease) may be common.
• Rifampin and rifabutin may decrease effectiveness of oral contraceptives.
• Ethambutol may cause amaurosis. Monitor patients monthly for visual acuity and color vision. (Ethambutol accumulates in patients with renal failure.)

Special Concerns

• A well-documented case of M xenopi disease should be published. Many cases described in the literature are probably only examples of colonization. In such cases, overtreatment of patients without true disease may result.

References

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Keywords

Mycobacterium xenopi, M xenopi, South African toad, Xenopus laevis, X laevis, nontuberculous mycobacterium, nontuberculous mycobacteria, mycobacteremia, leukocytosis, leucopenia, leukopenia, anemia, reactive thrombocytosis, thrombocytopenia, nontuberculous mycobacterial lung disease, pulmonary disease, cavitary apical pulmonary disease, multifocal bronchiectasis, granulomatous inflammation, acid-fast bacilli

Contributor Information and Disclosures

Author

Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus
Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Martin Backer, MD, Fellow in Combined Adult and Pediatric Infectious Diseases, State University of New York Health Sciences Center
Martin Backer, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Sailaja Kolli, MD, Fellow, Department of Internal Medicine, Division of Pulmonary and Critical Care, The Brooklyn Hospital Center
Sailaja Kolli, MD is a member of the following medical societies: American Medical Association
Disclosure: Nothing to disclose.

Klaus-Dieter Lessnau, MD, FCCP, Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital
Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Artificial Internal Organs, American Thoracic Society, Physicians for Social Responsibility, and Society of Critical Care Medicine
Disclosure: sepracor Ownership interest None

Medical Editor

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
Wesley W Emmons, MD, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, and International AIDS Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Aaron Glatt, MD, Professor of Clinical Medicine, New York Medical College; President and CEO, Former Chief Medical Officer, Departments of Medicine and Infectious Diseases, New Island Hospital
Aaron Glatt, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Infectious Diseases Society of America, International AIDS Society, and Society for Healthcare Epidemiology of America
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
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
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Clinical guidelines

Guidelines for environmental infection control in health-care facilities. Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee.
Centers for Disease Control and Prevention - Federal Government Agency [U.S.]. 2003 Jun 6. 42 pages. NGC:003059

Mycobacterial infections.
New York State Department of Health - State/Local Government Agency [U.S.]. 2005 May (revised 2006 Sep). 20 pages. NGC:006468

Clinical trials

Study of Mycobacterial Infections

Clarithromycin v Ciprofloxacin Added to Rifampicin + Ethambutol, for Opportunist Mycobacterial Pulmonary Disease

Related eMedicine topics

Atypical Mycobacterial Diseases

Atypical Mycobacterial Infection

Bronchiectasis

Bronchitis

Lung, Nontuberculous Mycobacterial Infections

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