Mycobacterium xenopi pneumonia in the Southeastern United States. (Case Report).

Abstract

Mycobacterium xenopi (M xenopi) is a slow-growing, nontuberculous mycobacterium (NTM), This organism is found in fresh water and has been isolated in water samples collected from water systems in homes and hospitals. Before the acquired immunodeficiency syndrome epidemic, M xenopi infection was infrequent and occurred in clusters; however, M. xenopi is now a recognized cause of pulmonary infection in immunocompetent patients with preexisting lung disease. The classic chest x-ray appearance is cavitary apical pulmonary disease, which mimics tuberculosis. M xenopi is currently one of the most common NTM pathogens in parts of England and Canada and has been reported in parts of the northeastern United States. Whether the isolation of M. xenopi from our patient in Tennessee represents a new geographic distribution of this organism or technologic advancements that now allow for reliable identification is debatable. This case serves as a reminder to clinicians that the incidence of NTM infection is rising in the United States and that unusual NTM are capable of causing disease even in patients who are not immunocompromised.

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The genus Mycobacterium contains more than 70 recognized or proposed species. These species can be divided into two groups based upon their growth rate in culture. (1) The slow-growing species require more than 7 days to form visible colonies on solid media, whereas the rapid-growing species require less than 7 days. Although there are important exceptions, the slow-growing species are often pathogenic in humans, whereas the rapid-growing species are usually considered nonpathogenic. Mycobacterium xenopi (M. xenopi) is a slow-growing, nontubercular mycobacterium (NTM). It is uncommon for it to be isolated from humans in the United States, but pulmonary infections caused by this organism have been recognized in patients residing in the Northeast. (2) Because infection from NTM is not a reportable disease in the United States, no reliable estimates of incidence or prevalence of M xenopi infection are available. (3) Our patient represents the first case of M xenopi respiratory infection to be reported from the s outheastern United States and should alert clinicians that unusual NTM pulmonary infections can occur in immunocompetent hosts.

Discussion

The acquired immunodeficiency syndrome (AIDS) epidemic led to the recognition of the M. aviunz-intercellulare complex as an important secondary infection and allowed the medical community to identify NTM as important respiratory pathogens. Although the incidence of M. tuberculosis infection has decreased in the United States, the incidence of lung disease caused by NTM has increased. (2,3,5) The reason for this observed increase in NTM infection is not thought to be solely because of the impact of the HIV epidemic. Possible additional contributing factors include climatic and environmental change, increased prevalence of chronic lung disease, immune senescence in an older population, or newer laboratory diagnostic techniques that have improved the isolation and identification of NTM. (6)

M. xenopi was first isolated from a skin granuloma of the toad Xenopus leavis in 1959. Since then, M. xenopi has been isolated in nature from water and soil. (2) In addition, this organism has been isolated from tap water systems and showerheads. Moreover, colonization of the hot water tank of an automated disinfection machine by M xenopi resulted in a pseudoepidemic of infection with this organism by contamination of fiberoptic bronchoscopes at a hospital in Michigan. (2) Respiratory infections in humans are believed to occur from environmental exposures; person-to-person transmission of M. xenopi is not thought to occur. It is not known whether M xenopi can lie dormant in the lungs without causing disease like its tubercular counterpart M. tuberculosis.

Nontuberculous mycobacterium infection varies geographically in both the prevalence of disease and the mycobacterial species responsible for disease. Mycobacterium avium-intercellulare complex and M. kansasii are the first and second most common NTM pulmonary pathogens in the United States. (3) Although the isolation of M. xenopi in the United States is relatively infrequent, this organism is the most common NTM pulmonary pathogen in parts of England and Canada. (6-8) M. xenopi is the second most common NTM species recovered from the respiratory tract of patients from Vienna, Austria. (9) This organism is also often recovered from the pulmonary secretions of patients from Japan, Slovakia, France, and Israel. (10-14) Respiratory infections caused by this organism have been reported in New York and Connecticut. (6,11,15,16) Our patient represents the first reported case of M. xenopi pneumonia in the southeastern United States.

Onset of symptoms from M. xenopi pulmonary infection is insidious, and symptoms may wax and wane for several months. Patients with respiratory disease caused by M. xenopi infection typically complain of a chronic productive cough, weakness, weight loss, and dyspnea; hemoptysis, night sweats, and fever are less common symptoms.

The classic radiographic appearance of M. xenopi pulmonary infection is a cavitary, apical pulmonary process. The cavities have thin walls, usually with little surrounding parenchymal infiltration. Lymphadenopathy and pleural effusions are rare roentgenographic findings. (16) Computed tomography of the thorax confirms the appearance on chest x-ray films of M. xenopi respiratory disease. (17)

The established risk factors for M. xenopi pulmonary infection include COPD, old age, alcoholism, bronchiectasis, previous tuberculosis, and chronic sinusitis. (18-20) Our patient was 67 years old with the risk factors of COPD and alcohol dependence. Patients with HIV infection are also at risk of this infection, and in this subset of patients the organism may disseminate.

The American Thoracic Society established criteria to aid the clinician in the diagnosis of NTM pulmonary infection. (4) Unfortunately, the identification of these organisms by classic laboratory methods (cultivation and biochemical tests) is time consuming and may result in a significant delay, as was illustrated by our patient. This delay may adversely affect patient care and outcome. The new generation of rapid nucleic acid amplification techniques, such as PCR, has allowed for the early diagnosis of M. tuberculosis and M aviumintracellulare, especially in patients with sputum samples that are positive for Mycobacterium species on AFB smears. (21-24) PCR results are available within 24 to 48 hours after the laboratory receives a specimen. If performed by experienced personnel, both the sensitivity and specificity of this test are high. (25) Similar assays for other NTM may follow. It is hoped that these new laboratory techniques will have a dramatic impact on our ability to rapidly and accurately diagnose NTM infection, including M. xenopi infection. For now, however, M. xenopi is identified by its unique pattern of mycolic acid on high-performance liquid chromatography.

The optimal therapy and duration of treatment for pulmonary disease caused by M. xenopi have not been established. In addition, the response of this organism to therapy is variable and does not always correlate well with the results of in vitro susceptibility testing. The mortality rate from M. xenopi pulmonary infection is as high as 57% (4) Although underlying disease may have played a part in the death rate of the patients in this report, the poor response to treatment is alarming. It has, therefore, been recommended that the patients with respiratory disease caused by M. xenopi be treated with multiple antitubercular medications and that therapy be guided more by side effects, drug tolerance, and clinical response than by in vitro sensitivities. The cornerstone of treatment for M. xenopi is a combination of rifampin and ethambutol. Treatment with macrolides and streptomycin may be of benefit, but other antimycobacterial drug therapies have not been studied adequately to make a firm statement concerning th eir efficacy. The addition of isoniazid in one study resulted in a nonsignificant decrease in treatment failures. (2) Our patient responded to the combination therapy of rifampin, ethambutol hydrochloride, and clarithromycin. Therapy should be continued until the patient has maintained sputum cultures negative for Mycobacteriurn species for 10 to 12 months. Although investigational, surgical resection of the affected lung may be appropriate in selected patients who have sufficient lung function and fail to respond to chemotherapy. (26-28)

As this case illustrates, M. xenopi respiratory infections clinically and radiographically often simulate tuberculosis. However, the clinical course, response to conventional antimycobacterial drugs, and the prognosis of respiratory disease caused by M. xenopi are important distinguishing features of M. xenopi lower respiratory disease. These differences between tuberculosis and M. xenopi infection emphasize the need for precise identification of the infecting mycobacterial organism. (29)

Accepted May 24, 2002.

References

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RELATED ARTICLE: Key Points

* A 67-year-old man presented with symptoms and radiographic findings mimicking pulmonary tuberculosis.

* Mycobacterium xenopi (M xenopi) was identified in sputum samples obtained from the patient.

* The incidence of M. xenopi infection varies geographically; it is infrequently reported as an infectious agent in the United States.

* Treatment of M. xenopi infection requires the use of multiple antitubercular medications.

Case Report

A 67-year-old white man who was a lifelong resident of Johnson City, Tennessee, complained of a 3-month history of cough productive of whitish sputum, fever, and night sweats. He also reported a 20-pound weight loss because of poor appetite. He had not traveled and had no risk factors for infection with the human immunodeficiency virus (HIV). His history was significant for alcohol dependence and chronic obstructive pulmonary disease (COPD) from tobacco use.

His temperature was 96.6[degrees] F, pulse rate was 72 beats/mm; blood pressure was 132/72 mm Hg; and respiratory rate was 20 breaths/mm. Auscultation of his lungs revealed poor air movement in all lung fields without crackles, wheezes, or rhonchi. Although the patient was thin, the remainder of the physical examination findings were normal.

Laboratory tests revealed a white blood cell count of 8,000/m[m.sup.3]. Hemoglobin concentration, hematocrit value, serum electrolyte levels, and biochemical survey were all in normal range. Test for HIV infection was negative. Immunoglobulin levels were normal. A chest x-ray demonstrated a focal air-space infiltrate in the right upper lobe (Fig. 1). Computerized tomography confirmed the infiltrate and documented fluid-filled cavities in the same area (Fig. 2). Sputum stained positive for acid-fast bacilli (AFB).

Tuberculosis was suspected clinically, and the patient was treated with oral rifampin (600 mg/d), isoniazid (300 mg/d), pyrazinamide (1,000 mg/d), and ethambutol hydrochloride (800 mg/d). Polymerase chain reaction (PCR) was positive for Mycobacterium genus but was negative for M tuberculosis and M avium-intracellulare. High-performance liquid chromatography identified M xenopi in three separate sputum samples, establishing the diagnosis of pulmonary infection by this NTM. (4) After M xenopi was identified as the pathogenic organism, treatment was changed to oral clarithromycin (500 mg twice a day), rifampin (600 mg/d), and ethambutol hydrochloride (dose was increased to 1,600 mg/d). Sputum AFB stain and cultures converted to negative for Mycobacterium species after 2 months of treatment.

From the Veterans Affairs Medical Center, Mountain Home, TN, and the Division of Pulmonary Medicine and Critical Care, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN.

Reprint requests to Ryland P. Byrd, Jr, MD, Veterans Affairs Medical Center, 111-B, P0 Box 4000, Mountain Home, Tennessee 37684-4000

Copyright [c] 2003 by The Southern Medical Association