Clinical review of pulmonary disease caused by Mycobacterium xenopi.

Mycobacterium xenopi comprised 56% of all non-tuberculous mycobacteria isolated in the Brompton Hospital laboratory during six years. M xenopi alone was cultured from the sputum of 23 patients, whose clinical and bacteriological features are reviewed. Pulmonary disease was considered to be due to the organism present in 15 of these patients on the basis of strict criteria for a causal relationship. Radiographs of all these patients were consistent with mycobacterial disease, showing pulmonary cavitation in 11, apical shadowing in three, and upper lobe fibrosis in one. In nine patients the disease was chronic, progressing very slowly with longstanding respiratory symptoms and extensive radiographic abnormalities developing over many years (mean 19 years). In six patients the disease was subacute, being of recent onset with radiographic shadowing of limited extent. M xenopi was isolated as a saprophyte from four patients who had lung disease of known cause and single isolates were obtained from four patients who had no lung disease attributable to this organism. In vitro drug sensitivity tests showed the sputum cultures of 17 of 22 patients to be sensitive to two or more of the drugs rifampicin, isoniazid, and ethambutol. Response to chemotherapy was unpredictable and did not always correlate with the results of sensitivity tests. Of 11 patients treated with at least two drugs to which their organisms were sensitive, two remained sputum positive, one relapsed after 18 months of chemotherapy, and eight have remained sputum negative during a minimum of three years' follow-up.     

Mycobacterial isolations in young adults with cystic fibrosis.

In 223 patients admitted to hospital with cystic fibrosis mycobacteria were found in the sputa of seven. All of these cases were identified over a six year period after the introduction of routine examination and culture of sputum for acid fast bacilli in patients with cystic fibrosis. The organisms isolated were Mycobacterium tuberculosis in three patients, M chelonei in one, M fortuitum in one, and unidentified mycobacteria in two. The diagnosis was not suspected on clinical grounds in any of the cases; in one patient, however, night sweats were a prominent feature before diagnosis. In four of the patients direct sputum smear examination did not reveal the organism, which was grown subsequently in culture. An unusual phenomenon of liquefaction of the Lowenstein-Jensen culture medium was encountered in five of the seven patients described, which in one case made identification and sensitivity testing of the organism impossible. This phenomenon has been observed in sputum cultures from other patients with cystic fibrosis but not in other pulmonary diseases. Immunological studies performed in three of the patients showed normal numbers of peripheral blood T and B lymphocyte in all three; in vitro lymphocyte transformation to tuberculin PPD was, however, reduced in the patient with extensive M fortuitum infection, which proved fatal. Mycobacteria may be present in the sputa of patients with cystic fibrosis more often than previously recognised and therefore sputum examination and culture for mycobacteria should be performed periodically in these patients.     

Disseminated visceral infection with Mycobacterium fortuitum in a hemodialysis patient

A 28-year-old patient with chronic renal failure on maintenance hemodialysis developed fever, granulomatous hepatitis, pulmonary infiltrates, sacroiliitis, and spondylitis which were unresponsive to conventional antituberculous treatment. Cultures of the sputum gave repeated growth of Mycobacterium fortuitum. This organism was resistant 'in vitro' to most antituberculous drugs and sensitive to some aminoglycosides and doxycycline. No mycobacteria were found in the water used for dialysis. The patient was successfully treated with amikacin and doxycycline. Nontuberculous mycobacterial infection should be considered in the differential diagnosis of febrile illnesses resembling tuberculosis in hemodialysis patients. Defective immune mechanisms could contribute to this complication. Since M. fortuitum is usually resistant to antituberculous drugs, precise identification and sensitivity testing are essential for optimal management.     

Pulmonary nocardiosis in a 3-year-old child

Until 1960, 179 cases of infection with Nocardia asteroides had been described in the world literature. Seventeen cases in children were reported by 1963. The organism is a common saprophyte in nature with probably a world-wide distribution. Infection can be primary but is more common in patients with underlying malignancy, auto-immune disease or preceding tuberculosis. Sulphonamides, particularly sulphadiazine, are the drugs of choice in treatment; the value of antibiotics is less clearly established. The indications for surgical treatment have not yet been defined. We record a further case of primary pulmonary nocardiosis in a 3-year-old child.     

Urine lipoarabinomannan as a marker for low-risk of NTM infection in the CF airway

BackgroundIndividuals with Cystic fibrosis (CF) are the most vulnerable population for pulmonary infection with nontuberculous mycobacteria (NTM). Screening, diagnosis, and assessment of treatment response currently depend on traditional culture techniques, but sputum analysis for NTM in CF is challenging, and associated with a low sensitivity. The cell wall lipoarabinomannan (LAM), a lipoglycan found in all mycobacterial species, and has been validated as a biomarker in urine for active Mycobacterium tuberculosis infection.MethodsUrine from a CF cohort (n = 44) well-characterized for NTM infection status by airway cultures was analyzed for LAM by gas chromatography/mass spectrometry. All subjects with positive sputum cultures for NTM had varying amounts of LAM in their urine. No LAM was detected in subjects who never had a positive culture (14/45). One individual initially classified as NTM sputum negative subsequently developed NTM disease 657 days after the initial urine LAM testing. Repeat urine LAM testing turned positive, correlating to her positive NTM status. Subjects infected with subspecies of M. abscessus had greater LAM quantities than those infected with M. avium complex (MAC). There was no correlation with disease activity or treatment status and LAM quantity. A TB Capture ELISA using anti-LAM antibodies demonstrated very poor sensitivity in identifying individuals with positive NTM sputum cultures.ConclusionThese findings support the conclusion that urine LAM related to NTM infection may be a useful screening test to determine patients at low risk for having a positive NTM sputum culture, as part of a lifetime screening strategy in the CF population.     

Surgical management of multidrug-resistant tuberculosis

We report surgical resections in 3 patients with active multidrug-resistant tuberculosis. All cases involved strains of Mycobacterium tuberculosis resistant to at least isoniazid and rifampin and patients who were poor candidates for medical therapy alone. We conducted pulmonary resections (partial resection in case I, lobectomy in case 2, and segmentectomy in case 3). The optimum multiple-drug regimen, based on drug susceptibility studies, was used preoperatively and postoperatively. In all cases, sputum smears and cultures yielded negative results postoperatively, and continue to be negative for Mycobacterium tuberculosis to date. It is recomended that, if localized disease is present and medical treatment is likely to fail, pulmonary resection be conducted for multidrug-resistant Mycobacterium tuberculosis.     

Surgical management of multidrug-resistant tuberculosis.

We report surgical resections in 3 patients with active multidrug-resistant tuberculosis. All cases involved strains of Mycobacterium tuberculosis resistant to at least isoniazid and rifampin and patients who were poor candidates for medical therapy alone. We conducted pulmonary resections (partial resection in case 1, lobectomy in case 2, and segmentectomy in case 3). The optimum multiple-drug regimen, based on drug susceptibility studies, was used preoperatively and postoperatively. In all cases, sputum smears and cultures yielded negative results postoperatively, and continue to be negative for Mycobacterium tuberculosis to date. It is recommended that, if localized disease is present and medical treatment is likely to fail, pulmonary resection be conducted for multidrug-resistant Mycobacterium tuberculosis.     

The analysis of surgically treated pulmonary tuberculosis

Between January 1990 and December 1999, thirteen patients with pulmonary tuberculosis underwent surgical management in our hospital. The purpose of surgery was classified into three groups: drug-resistant or persistent disease (7 patients), hemoptysis (3), and the others. We have no operative death, but have two late deaths due to postoperative persistent positive sputum and progressive tuberculosis infection. One patient relapsed one year and six months after operation and medical treatment was done successfully. Pulmonary resection is useful for localized pulmonary tuberculosis even drug-resistant cases.     

Surgical treatment of nontuberculous mycobacterial lung disease

While the prevalence of pulmonary tuberculosis has been decreasing, the prevalence of nontuberculous mycobacterial lung disease has been increasing. Unlike tuberculosis, nontuberculous mycobacterial disease is not communicable. However, their indolent nature may result in extensive parenchymal destruction, causing respiratory failure and vulnerability to airway infection. Nontuberculous mycobacterial lung disease, therefore, has been becoming a significant health problem. According to the 2007 American Thoracic Society/Infectious Diseases Society of America statement on nontuberculous mycobacterial diseases, the primary treatment is a multidrug treatment regimen. However, its efficacy is less than satisfactory for Mycobacterium avium complex lung disease, which is the most common type of nontuberculous mycobacterial lung diseases, and for Mycobacterium abscessus lung disease, which is notoriously resistant to chemotherapeutic drugs. The statement, therefore, has proposed a multidisciplinary treatment approach for these types of nontuberculous mycobacterial lung diseases: a combination of multidrug treatment regimen and adjuvant resectional surgery. This review covers the rationale, indication, procedure, and outcome of surgical treatment of nontuberculous mycobacterial lung disease. The rationale of surgery is to prevent disease progressing by removing the areas of lung most affected, harboring the largest amounts of mycobacteria. The indications for surgery include a poor response to drug therapy, the development of macrolide-resistant disease, or the presence of a significant disease-related complication such as hemoptysis. The surgical procedures of choice are various types of pulmonary resections, including wedge resection, segmentectomy, lobectomy, or pneumonectomy. The reported series have achieved favorable treatment outcomes in surgically treated patients with acceptable morbidity and mortality rates.     

Surgery increased the chance of cure in multi-drug resistant pulmonary tuberculosis.

BACKGROUND: Medical treatment of multiple drug resistant (MDR) pulmonary tuberculosis is generally quite unsuccessful. Recently, surgical management is increasing and shows promise. We analyzed our experience to identify the benefits and complications of pulmonary resection in MDR pulmonary tuberculosis. METHODS: A retrospective review was performed in 27 patients undergoing pulmonary resection for MDR pulmonary tuberculosis between January 1994 and March 1998. Their average ages were 40 years and were diagnosed a median of 15 months before surgery. All patients had resistance to an average of 4.4 drugs including isoniazid and rifampin, and had received second line drugs selected according to drug sensitivity test preoperatively. Most patients (92.6%) had cavitary lesions. Bilateral lesions were also identified in 19 patients (70.4%), but the main focus was recognized in one side of the lung. Most patients were indicated to operation for those who could not achieve negative sputum despite adequate medical treatment (n = 16, 59.3%); or for negative patients who had significant pulmonary parenchymal lesion (n = 11, 40.7%) which would have had a high probability of recurrence. Pneumonectomy was done in nine patients, lobectomy in 16 and segmentectomy in two. RESULTS: There was no operative mortality. Morbidity occurred in seven patients (25.9%); prolonged air leakage in three patients, reoperation due to bleeding in two, bronchopleural fistula in one, and reversible blindness in one. The median follow up period was 15 months (range 3-45). Sputum negative conversion was achieved in 22 patients (81.5%) initially. However, continued postoperative chemotherapy could convert to negative in another four patients (14.8%). Only one pneumonectomy patient (3.7%) failed because of considerable contralateral cavity. CONCLUSION: For patients with MDR pulmonary tuberculosis which is localized, and with adequate pulmonary reserve function, surgical pulmonary resection combined with appropriate pre and postoperative anti-tuberculosis chemotherapy can achieve high success rate with acceptable morbidity.     

Combined versus single antituberculosis drugs on the in vitro sensitivity patterns of non-tuberculous mycobacteria.

Drug sensitivity tests were performed for ethambutol, rifampicin, streptomycin, and isoniazid both alone and in paired combinations, on 16 strains of Mycobacterium avium intracellulare, seven strains of Mycobacterium xenopi, and eight strains of Mycobacterium malmoense. Most strains were resistant to the individual drugs, but all strains of M malmoense, 86% of M xenopi, and 31% of M avium intracellulare were completely suppressed by the lowest concentrations of ethambutol and rifampicin when the two drugs were combined in vitro. Streptomycin combined with ethambutol or with rifampicin in the lowest combined concentrations suppressed 50% and 62% respectively of strains of M malmoense. All strains of M xenopi were suppressed by the lowest combined concentrations of streptomycin with rifampicin. Combinations with isoniazid were less effective. It is postulated that similar effects in vivo might account for the satisfactory clinical response seen in patients with disease caused by these mycobacteria who have received treatment with combinations of standard antituberculosis drugs despite in vitro resistance to the individual agents.     

Management of pulmonary aspergilloma in the presence of active tuberculosis

Eleven cases of pulmonary aspergilloma complicating active cavitating pulmonary tuberculosis are reviewed. Nine of the 10 patients who had combined medical (antituberculosis drugs) and surgical treatment were cured of their disease; one patient, who had bilateral multiple aspergillomas, died from massive haemoptysis after resection of one of the affected lobes. The only medically treated patient who refused surgery had fatal haemoptysis at home. Pulmonary resection is recommended for patients who are fit for operation whenever the diagnosis of aspergilloma is made because most published reports indicate that only a few patients benefit from drug treatment alone.     

The fungal airway microbiome in cystic fibrosis and non-cystic fibrosis bronchiectasis

BackgroundThe prevalence of fungal disease in cystic fibrosis (CF) and non-CF bronchiectasis is increasing and the clinical spectrum is widening. Poor sensitivity and a lack of standard diagnostic criteria renders interpretation of culture results challenging. In order to develop effective management strategies, a more accurate and comprehensive understanding of the airways fungal microbiome is required. The study aimed to use DNA sequences from sputum to assess the load and diversity of fungi in adults with CF and non-CF bronchiectasis.MethodsNext generation sequencing of the ITS2 region was used to examine fungal community composition (n = 176) by disease and underlying clinical subgroups including allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, non-tuberculous mycobacteria, and fungal bronchitis. Patients with no known active fungal disease were included as disease controls.ResultsITS2 sequencing greatly increased the detection of fungi from sputum. In patients with CF fungal diversity was lower, while burden was higher than those with non-CF bronchiectasis. The most common operational taxonomic unit (OTU) in patients with CF was Candida parapsilosis (20.4%), whereas in non-CF bronchiectasis sputum Candida albicans (21.8%) was most common. CF patients with overt fungal bronchitis were dominated by Aspergillus spp., Exophiala spp., Candida parapsilosis or Scedosporium spp.ConclusionThis study provides a framework to more accurately characterize the extended spectrum of fungal airways diseases in adult suppurative lung diseases.     

Complicated hydatid cysts of the lung: clinical and therapeutic issues

BACKGROUND: The clinical presentation and the preoperative and postoperative complications associated with pulmonary hydatid cysts depend on whether the cyst is intact or ruptured. The aim of this study was to review the problems encountered in treating ruptured pulmonary hydatid cysts and to highlight the risks associated with chemotherapy and the delay of surgical treatment in pulmonary hydatid disease. METHODS: The medical records for 67 patients of pulmonary hydatidosis were retrospectively investigated. The patients were divided into two groups based on whether the pulmonary cyst was intact (group 1, n = 34) or complicated (group 2, n = 33). A complicated cyst was defined as one that had ruptured into a bronchus or into the pleural cavity. All patients were treated surgically. Data related to symptoms, preoperative complications, surgical procedures performed, postoperative morbidity, hospitalization time, and cyst recurrence were collected from each individual's records, and the group findings were compared. RESULTS: In most cases of intact pulmonary hydatid cysts, the lesions were either incidental findings or the patient had presented with cough, dyspnea and chest pain. In addition to these symptoms, the patients with complicated cyst had presented with problems such as expectoration of cystic contents, repetitive hemoptysis, productive sputum, and fever. The differences between the groups with respect to the rates of preoperative complications and postoperative morbidity, frequency of decortication, and hospital stay were statistically significant (p < 0.05). CONCLUSIONS: Surgery is the primary mode of treatment for patients with pulmonary hydatid disease. Complicated cases have higher rates of preoperative and postoperative complications and require longer hospitalization time and more extensive surgical procedures than uncomplicated cases. This underlines the need for immediate surgery in any patient who is diagnosed with pulmonary hydatidosis.     

Comparison of characteristics of patients and treatment outcome for pulmonary non-tuberculous mycobacterial infection and pulmonary tuberculosis.

BACKGROUND: Patients with non-tuberculous mycobacteria are usually started on conventional antituberculous triple therapy once acid fast bacilli are detected, before the exact type of mycobacteria has been identified. The ability to identify the characteristics of patients with tuberculous and non-tuberculous mycobacteria may be helpful in identifying before treatment those patients more likely to have non-tuberculous infection. METHODS: A retrospective study was conducted of all patients in one unit in whom non-tuberculous mycobacteria were identified in sputum or bronchoalveolar washings in the period 1987-93. The pattern of drug resistance was determined from laboratory records, and all case notes and chest radiographs were reviewed to identify the underlying disease and treatment outcome. All cases were compared with a matched control group of patients with culture positive Mycobacterium tuberculosis diagnosed during the same period. RESULTS: In the period studied there were 70 non-tuberculous and 221 tuberculous isolates. The non-tuberculous bacteria were typed as follows: M xenopi 23 (33%), M kansasii 19 (27%), M fortuitum 14 (20%), others 14 (20%). Of those with non-tuberculous mycobacteria, 83% were white subjects compared with 47% for tuberculosis. Patients with non-tuberculous mycobacteria were older than those with tuberculosis. Pre-existing lung disease or AIDS was present in 81% of patients with non-tuberculous mycobacteria and in 17% of patients with tuberculosis. Sensitivity to rifampicin and ethambutol was seen in 95% of M xenopi and 96% of M kansasii isolates. Relapse occurred in 60% of cases infected with M xenopi, 20% infected with M kansasii, and in 7% of cases with tuberculosis. CONCLUSIONS: In the population studied non-tuberculous mycobacteria occurred most frequently in elderly white subjects with pre-existing lung disease. If mycobacteria are detected in this group, consideration should be given to the possibility of non-tuberculous infection before embarking on treatment. A combination containing rifampicin and ethambutol is effective. The relapse rate for infection with M xenopi is high and prospective studies of the effect of the above combination of antituberculosis drugs are needed.     

Prise en charge d’une colite aigüe grave

Acute severe colitis is a classic complication of inflammatory bowel disease, especially of ulcerative colitis. It is a short-term life-threatening medical and surgical emergency. Acute severe ulcerative colitis diagnosis is based on clinical and biological criteria. The first medical evaluation should identify serious complications that require surgery in emergency and exclude a bowel infection (especially Clostridium Difficile or cytomegalovirus infections). In acute severe colitis, intravenous corticosteroids are the conventionnal medical treatment. However, roughly one third of patients are resistant to the treatment. Ciclosporin and infliximab are potential rescue treatments in this case, with a similar efficacy. Colectomy remains the best option in case of complicated acute severe colitis and should be discussed as an option at each stage of the treatment.     

Crescentic Glomerulonephritis Associated with Non-Tuberculous Mycobacteria Infection

A 72-year-old woman with a previous diagnosis of non-tuberculous mycobacteria (NTM) pulmonary disease was admitted because of hemoptysis and acute renal failure. A chest x-ray showed interstitial infiltration over bilateral lung fields. A kidney biopsy showed immune complex-mediated crescentic glomerulonephritis and diffuse endocapillary hypercellularity with exudative neutrophils. Reactive NTM infection of the lungs was suspected when mycobacterial cultures of the sputum repeatedly yielded Mycobacterium avium. A lung biopsy revealed chronic inflammation without evidence of alveolar capillaritis. NTM pulmonary disease was further confirmed by tissue culture of the lung biopsy specimens. Anti-tuberculous drugs in combination with clarithromycin were given for the treatment of NTM infection. Because of the risk of aggravating underlying infectious disease, immunosuppressive therapy for crescentic glomerulonephritis was not carried out. Pulmonary symptoms promptly responded to treatment. Furthermore, renal function steadily improved after the initiation of anti-NTM therapy. To our knowledge, this is the first report of crescentic glomerulonephritis associated with NTM infection.     

A comparative evaluation of drug combinations used in the treatment of pulmonary tuberculosis

A retrospective analysis was undertaken of the hospital records of 185 patients admitted for the first time for treatment of pulmonary tuberculosis. The time to sputum conversion was used to evaluate the efficacy of short-course antituberculosis therapy and to determine the effect of including rifampicin (RMP) in various chemotherapeutic combinations. RMP per se was not found to be a significant variable in the drug combinations studied. The combination of RMP and pyrazinamide, however, showed greater efficacy in achieving earlier sputum conversion. The therapeutic advantage of using these two drugs in combination should be more readily appreciated.     

Surgical treatment of primary pulmonary sarcomas.

OBJECTIVE: We sought to identify the long-term prognosis after surgical treatment for primary pulmonary sarcoma. METHODS: Twenty-three patients were retrospectively identified as having been treated surgically for primary pulmonary sarcoma between 1981 and 1996. The records of all patients were reviewed, and the histopathology reexamined by a pathologist. RESULTS: Fifteen patients were male and eight female; their ages ranged from 20 to 78 (mean 51) years. Tumors measured between 0.9 and 12.0 (mean 5.2) cm across the greatest diameter. The histologic diagnoses were malignant fibrous histiocytoma (8, three grade 1 or 2, two grade 3), synovial sarcoma (4), malignant schwannoma (3), leiomyosarcoma (3), and one case each of angiosarcoma, intimal sarcoma, epitheloid hemangioendothelioma, fibrosarcoma and primitive neuroectodermal tumor. Three patients were found to be unresectable. All three underwent radiation and chemotherapy. Lobectomies or bilobectomies were performed in 13 patients including two sleeve resections, one carinal resection, and one chest wall resection. Four patients underwent radical pneumonectomies. Three patients with invasion of the pulmonary artery, pulmonary veins or atrial wall underwent extended resections with the use of cardiopulmonary bypass. In two, a homograft was used to reconstruct the right ventricular outflow tract. Of the resected patients, six had a positive resection margin, and four had at least one positive lymph node in the specimen. Three patients underwent repeat pulmonary resections for recurrences. Eleven patients received postoperative chemotherapy and eight had radiation therapy. Follow-up was available on 22 patients, and ranged from 2 to 183 (mean 48) months; 14 patients are disease free, six died of disease, one died of surgical complications (operative mortality 5%), and two are alive with disease. Actuarial 3- and 5-year survival of the resected patients was 69%. Size and grade were not found to be correlated with significantly increased survival, but completeness of resection was (P<0.05). CONCLUSIONS: Resection of primary pulmonary sarcomas can produce an acceptable survival rate if the resection is complete. Cardiopulmonary bypass can be a useful adjunct when tumors involve a resectable area of the heart or great vessels.     

Surgical treatment in bronchiectasis: analysis of 166 patients.

BACKGROUND: Bronchiectasis is usually caused by pulmonary infections and bronchial obstruction. It is still a serious problem in developing countries as our country. We reviewed the morbidity and mortality rates and outcome of surgical treatment for bronchiectasis. PATIENTS AND METHODS: Between 1990 and 2000, 166 patients (92 female and 74 male patients) underwent pulmonary resection for bronchiectasis. The mean age was 34.1 years (range, 7-70 years). Mean duration of symptoms was 5.7 years. RESULTS: Symptoms were copious amount of purulent sputum in 135 patients, expectoration of foul-smelling sputum in 109, hemoptysis in 35 and cough in all patients. The indication for pulmonary resection was failure of medical therapy in 158 patients, massive hemoptysis in five and lung abscess in three. The disease was bilateral in six patients and mainly confined to the lower lobe in 127. One hundred and twenty patients had a lobectomy, 13 had a pneumonectomy, 21 had a segmentectomy and a combination of these approaches in 18. Operative morbidity and mortality were seen in 18 (10.5%) and in three (1.7%) patients, respectively. Follow-up was complete in 148 patients with a mean of 4.2 years. Overall, 111 patients were asymptomatic after surgical treatment, symptoms were improved in 31, and unchanged or worse in six. CONCLUSIONS: Surgical treatment of bronchiectasis is more effective in patient with localized disease. It is satisfactory with acceptable ratio of morbidity and mortality.