Treatment of Pulmonary M xenopi Infection

Abstract & Commentary

Synopsis: Treatment of pulmonary M xenopi infection with isoniazid and rifampin, with or without ethambutol, appeared to be only modestly effective.

Source: Jenkins PA, Campbell IA; Research Committee of the British Thoracic Society. Pulmonary disease caused by Mycobacterium xenopi in HIV-negative patients: Five-year follow-up of patients receiving standardized treatment. Respir Med. 2003;97:439-444.

Jenkins and colleagues in the British Thoracic Society randomized 42 HIV-negative adults with pulmonary infection due to Mycobacterium xenopi to receive either rifampin plus isoniazid or this combination plus ethambutol. The medications were given daily for 2 years. No difference in outcome between the regimens was found, although the study had limited power to detect such a difference. Jenkins et al, therefore, reported the results for the entire group of 42 patients without regard to treatment regimen.

The mean age of the patients was 65 years and two-thirds had previous or co-existing lung disease, including chronic bronchitis, emphysema or asthma (13), healed tuberculosis (5), pneumonia (4), and bronchiectasis (3). Eleven patients had possible immunocompromise and 7 had "worked in dusty occupations." One patient had previously received BCG. The pulmonary disease was extensive in 38%, and 81% had cavities, mostly large. Sixty-two percent were smear positive.

Patients were monitored for 5 years. There were 3 treatment failures and 2 relapses after apparently successful treatment. Two patients were lost to follow-up. Sixty-nine percent died within the 5-year follow-up, but only 10% died as the result of mycobacterial infection. Only 7 patients (17%) were known to be alive and free of M xenopi infection at 5 years.

In vitro susceptibility testing was performed on the initial isolates from 29 patients. One-third were resistant to rifampin, 86% were resistant to isoniazid, and 70% were resistant to ethambutol. There was, however, no correlation between failure of therapy and in vitro resistance.

Comment by Stan Deresinski, MD, FACP

M xenopi is a cause of slowly progressive pulmonary infection, most often in patients with underlying lung disease, but it may also be present as a commensal. However, repeated isolation of this organism in the presence of pulmonary lesions can generally be taken as evidence that it is playing a pathogenic role.1 The laboratory should take care, however, in distinguishing M xenopi from the relatively recently identified Mycobacterium celatum, a distinction that cannot be made on the basis of biochemical tests alone.2

This paper reports the results of a valiant attempt to perform a randomized trial of treatment of an uncommon infection. Unfortunately, only 42 patients could be enrolled in 5 years, making any likelihood of finding a significant difference between these 2 relatively similar regimens quite unlikely. Furthermore, the clinical isolates were largely resistant in vitro to all 3 drugs studied. In vitro resistance, however, did not predict treatment failure, a result that was quite commonly observed.

Experiments with a murine model of M xenopi found that the 3-drug regimen used in the study reviewed, rifampin-isoniazid-ethambutol, was significantly less effective than clarithromycin alone. Recent reports have indicated that M xenopi is often susceptible to clarithromycin, amikacin,3 and linezolid (2002 ICAAC Abstract E-535). Seventeen isolates tested were highly susceptible to moxifloxacin (MICs < 0.47 mcg/mL) and gatifloxacin (< 0.32 mcg/mL), but 10 isolates were resistant to levofloxacin (2002 IDSA Abstract 694). Thus, there are a variety of drugs available from which to construct a rational regimen for treatment of M xenopi infection. In addition, surgical resection provides an alternative therapeutic approach in some patients with localized nodular or cavitary disease, especially if they fail chemotherapy, or in patients intolerant to antimicrobial therapy.4

Dr. Derenski is Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center.

References

1. Jiva TM, et al. Mycobacterium xenopi: Innocent bystander or emerging pathogen? Clin Infect Dis. 1997;24:226-232.

2. Zurawski CA, et al. Pneumonia and bacteremia due to Mycobacterium celatum masquerading as Mycobacterium xenopi in patients with AIDS: An underdiagnosed problem? Clin Infect Dis. 1997;24:140-143.

3. Dauendorffer JN, et al. In vitro sensitivity of Mycobacterium xenopi to five antibiotics. Pathol Biol. 2002;50:591-594.

4. Lang-Lazdunski L, et al. Pulmonary resection for Mycobacterium xenopi pulmonary infection. Ann Thorac Surg. 2001;72:1877-1882.