Mycobacterium chelonae empyema in an immunocompetent patient

Non-tuberculosis mycobacteria (NTM) are ubiquitous organisms that rarely cause disease in immunocompetent individuals. They are not transmissible from person to person. However, over the past two decades, there has been an increase in the number of cases of mycobacterial infections caused by non-tuberculous species, especially by rapidly growing mycobacteria (RGM) such as Mycobacterium chelonae, Mycobacterium abscessus and Mycobacterium fortuitum. The clinical features of NTM disease are indistinguishable from those of tuberculosis, so diagnosis requires culture and identification of the bacilli (American Thoracic Society, 1997). Patients with RGM pulmonary disease tend to be middle-aged or older, female and non-smokers (Griffith et al., 1993). Specific underlying diseases, such as prior mycobacterial infection, gastro-oesophageal disorders with chronic vomiting and bronchiectasis, occur in approximately 20 % of RGM patients (Griffith et al., 1993; Wallace et al., 1983). Only two cases of empyema of the pleural cavity caused by RGM (M. abscessus and M. fortuitum) have been reported (Aronchick et al., 1986; Fairhurst et al., 2002). Here, we report a rare case of thoracic empyema and bronchopleural fistula caused by M. chelonae in an immunocompetent woman. These case experiences indicate the emergence of RGM as causative pathogens of thoracic empyema, even in healthy persons.

Case report
A 53-year-old healthy female, without underlying disease or a history of tobacco use or immunosuppressant therapy, initially presented with a 4 week history of a severe cough with sticky yellowish sputum and no haemoptysis. She was treated as a pneumonia case by intravenous ampicillin (2 g, six times daily) and gentamicin (180 mg, once daily) in a community hospital for 1 week and her fever subsided. No pathogen was isolated from either sputum or blood specimens. However, the patient's fever recurred shortly after discharge and she was sent to a medical centre. As a result of the recurrence of pneumonia and right middle lung infiltration with atelectasis, as shown by chest X-ray, bronchoscopy was performed, and revealed right B6 orifice stenosis and swelling with redness. Acid-fast staining of smears and cultures from biopsy, bronchial lavage and three consecutive specimens of sputum were carried out. One specimen of biopsy revealed granulomatous inflammation with positive acid-fast bacilli (Fig. 1). Mycobacterium sp. was isolated from another sputum specimen. The patient received a complete course of anti-tuberculosis treatment for 9 months with isoniazid, rifampicin and ethambutol, according to the susceptibility results.

(158K): Fig. 1. Granulomatous inflammation characterized by infiltration of epithelioid histiocytes in the ulcerated mucosa (haematoxylin and eosin stain, magnification x40). Inset, several mycobacteria demonstrated by an acid-fast stain (magnification x100).

Six months later, the patient again presented with a productive cough, haemoptysis and an intermittent fever. She was admitted to our hospital and acid-fast bacilli were again found in her sputum. An initial chest X-ray was suggestive of a right pleural effusion and a high level of infiltration of the right lower lobe. This finding led to a computed tomography examination of the chest, which revealed a right-sided empyema, ipsilateral pleural thickening with several calcified patches, and multiple bronchiectasis with linear interstitial-pattern lesions in the right lung. A chest tube was subsequently inserted and about 200 ml dark-reddish pus was retrieved. The empirical regimen was changed to isoniazid plus rifampicin, ethambutol and ciprofloxacin to prevent the potential emergence of multidrug-resistant M. tuberculosis after the full course of anti-tuberculosis therapy. Because of the longer disease duration and unknown immune status, further evaluation was carried out and revealed no human immunodeficiency virus infection, and normal CD4 cell counts and immunoglobulin levels.

Two weeks later, M. chelonae was cultured from both pleural effusions and sputum on Lowenstein–Jensen medium, and identified by PCR/restriction enzyme pattern analysis (Telenti et al., 1993). We performed a thoracotomy with decortication and wedge resection of the right middle lung, as air leakage was found in this lobe, and a bronchopleural fistula was found during the operation. As there was no previous treatment experience reported in the literature, we prescribed oral clarithromycin plus ciprofloxacin therapy for 36 months until there were no symptoms/signs and negative sputum studies were observed for 6 months. The patient has not suffered a relapse in the 3 years since the cessation of treatment.

This was a rare case of pulmonary empyema and bronchopleural fistula induced by M. chelonae in a healthy female, followed by successful treatment. M. chelonae can infect numerous tissues, including the skin, soft tissues, skeleton and regions in contact with a catheter. Among these, soft-tissue and cutaneous diseases are the most common. The characteristic presentation in immunocompromised patients is a disseminated cutaneous infection (Wallace et al., 1992), and in immunocompetent patients it is localized cellulitis or abscesses (Brown-Elliott & Wallace, 2002; Zaleznik & Quinn, 1996). Whilst M. abscessus and M. fortuitum commonly cause pulmonary diseases, M. chelonae is not associated with these. Griffith et al. (1993) reported that, of 154 patients who presented with chronic lung diseases due to RGM, only 1 out of 146 isolates that were identified to the species level was M. chelonae. However, according to a study of pulmonary M. chelonae infection, all 14 patients were middle-aged or elderly women (range 40–85 years, mean 60 years) who did not have any other co-existing parenchymal lung disease (Hazelton et al., 2000). None was overtly immunocompromised. To date, there is no significant evidence to suggest why pulmonary disease caused by M. chelonae would occur in immunocompetent patients.

Chronic pulmonary disease is the most common localized clinical manifestation of NTM. Mycobacterium avium and Mycobacterium kansasii are the two most common pathogens in the USA (American Thoracic Society, 1997). The isolation of an NTM species from a respiratory sample is insufficient for a diagnosis of NTM lung disease. Instead, the diagnosis is based on clinical, radiographic and bacteriological criteria (American Thoracic Society, 1997). In addition, NTM cutaneous infection caused by surgical procedures (especially augmentation mammaplasty or median sternotomy) and accidental trauma, disseminated disease with multiple nodular skin lesions, positive blood cultures, cervical lymphadenitis, keratitis and endocarditis associated with a prosthetic valve have also been reported (Wallace et al., 1983).

Our patient was initially diagnosed as having tuberculosis by positive acid-fast staining and by the presence of Mycobacterium sp. in the sputum. The patient's symptoms resolved following a complete course of multiple anti-tuberculosis drugs. However, the disease eventually recurred and presented with a more complicated pulmonary infection. This might be attributed to an incomplete response and failure of the traditional anti-tuberculosis treatment. Although the initial episode of this patient as tuberculosis could not be excluded completely, it is possible that the initial Mycobacterium sp. infection was caused by M. chelonae, and the complicated nature of this infection suggested a prolonged course of treatment. Therefore, we pursued a more careful identification of the microbial species and their drug susceptibilities. In addition, because M. chelonae can be isolated from the water of bronchoscope washers (Kressel & Kidd, 2001), we could not completely exclude the possibility of superinfection by a contaminated bronchoscope or water used during the procedure. However, we surveyed other patients receiving a bronchoscopy for 1 month before and after the date that our patient received this examination, and none of these patients developed a disease related to M. chelonae.

Complicated pulmonary diseases caused by RGM are rare. Such diseases are more typically caused by M. abscessus or M. fortuitum (Griffith et al., 1993). Patients who have chronic pulmonary disease, bronchiectasis, cystic fibrosis or chronic obstructive pulmonary disease are always predisposed to develop RGM pulmonary infections. Only two cases of thoracic empyema caused by RGM have been reported. These cases were a lung transplant recipient infected with M. abscessus (Fairhurst et al., 2002) and an achalasia patient infected with M. fortuitum (Aronchick et al., 1986). Both patients had underlying disorders that predisposed them to infection. We report here what is believed to be the first case of severe pulmonary disease combined with empyema and bronchopleural fistula caused by M. chelonae in a healthy patient.

In most cases of pulmonary tuberculosis, the lesions are present in the apical or posterior segment of the upper lobes or the superior segment of the lower lobes. However, in NTM pulmonary diseases, the radiological picture is that of nodular bronchiectasis, involving predominantly the middle lobe and lingula (Chalermskulrat et al., 2002). In our patient, the initial lesion was involved in the right middle lobe and the bronchoscope revealed B6 orifice redness and stenosis. It was difficult to differentiate between tuberculosis and NTM infection, as both the right middle lobe and the superior segment of the right lower lobe were involved. However, in the later complicated pulmonary disease stage, the clinical and radiological presentations were compatible with NTM infections.

In the study by Hazelton et al. (2000) of computed tomography findings of pulmonary M. chelonae infection, bronchiectasis (93 %), nodules (93 %), consolidation (79 %), atelectasis (71 %), lymphadenopathy (57 %) and cavities (43 %) were found in 14 patients. In addition, in all but two patients, the presence of bronchiectasis was evenly distributed in the lung lobes. However, in our patient bronchiectasis was discovered only in the right lung. According to this study, M. chelonae may affect patients with diffuse bronchiectasis rather than cause bronchiectasis, although the latter was more compatible with our patient's presentation.

A treatment strategy for complicated pulmonary diseases has not yet been established. Only one clinical trial on the successful treatment of M. chelonae skin infection used clarithromycin (Wallace et al., 1993). We effectively employed a prolonged therapy with clarithromycin plus ciprofloxacin, which was shown to be effective in another patient with cutaneous infection (Chalermskulrat et al., 2002). However, a high prevalence of drug resistance in M. chelonae clinical isolates was recently reported in northern Taiwan (Yang et al., 2003). In that study, 100 % (39) isolates of M. chelonae were susceptible to amikacin, 82 % to linezolid, 49 % to clarithromycin and none to ciprofloxacin. Other literature also supports the use of multidrug therapy for the treatment of NTM infections (Driscoll & Tyring, 1997; Franck et al., 1993; Wallace et al., 1993; Zahid et al., 1994). Therefore, prolonged therapy for a complicated pulmonary infection caused by M. chelonae may be necessary in our experience, and combination therapy of clarithromycin with either amikacin or linezolid would be suggested in the future, following our regional resistance report (Yang et al., 2003) and published treatment studies for M. abscessus (Mushatt & Witzig, 1995) and M. fortuitum (Dalovisio et al., 1981; McFarland & Kuritzkes, 1993). However, the treatment strategy for M. chelonae pulmonary diseases still needs more prospective studies for reference.

Conclusion
In summary, NTM have emerged recently as significant clinical pathogens. Accurate diagnosis and identification of the mycobacterial species are critical for effective treatment of NTM. In addition, M. chelonae should be considered as a causative pathogen for complicated thoracic empyema with bronchopleural fistula, even in healthy patients. Furthermore, for treating this type of infection, prolonged combination therapy with the choice of drugs determined by regional susceptibility may be considered, although this requires further research.

We thank pathologist Kun-Bow Tsai for his many suggestions in the histology imaging of bronchoscopic specimens.