Surgical management of resistant mycobacterial tuberculosis and other mycobacterial pulmonary infections

Between August 1983 and October 1990, 42 patients with resistant Mycobacterium tuberculosis underwent 44 pulmonary resections. During the same time, 38 patients with mycobacterial infections other than tuberculosis had 41 pulmonary resections. All patients either were poor candidates for medical therapy alone or had existing complications requiring surgical intervention. There was one operative death in each group, both from adult respiratory distress syndrome (postpneumonectomy pulmonary edema). Complications were high, with bronchopleural fistula most commonly occurring after right pneumonectomy in patients infected with Mycobacterium avium with superimposed infection with nonmycobacterial pathogens. In patients undergoing pneumonectomy for resistant Mycobacterium tuberculosis, the left lung was most often resected. It is recommended that if localized disease is present and medical treatment is likely to fail, pulmonary resection should be performed for resistant Mycobacterium tuberculosis infection after 3 months of drug-specific therapy. Muscle flaps were used frequently to avoid residual space and bronchial stump problems. Earlier resection in patients with indolent nontuberculous mycobacterial pulmonary infections is advocated before extensive polymicrobial contamination and right lung destruction.     

Pneumonectomy for nontuberculous mycobacterial infections

Background

Pneumonectomy is considered in the treatment of nontuberculous mycobacterial infections when an entire lung is affected. However, this procedure carries high morbidity. We report on our experience in using pneumonectomy for treating patients with nontuberculous mycobacterial infections.

Methods

Between 1983 and 2002, 53 patients infected with nontuberculous mycobacteria underwent 55 pulmonary resections. Of these patients, 11 (3 men, 8 women) underwent pneumonectomy (5 right, 6 left). Median age was 57 years (range, 43 to 69 years). Mycobacterium avium complex disease occurred in 10 patients and Mycobacterium abscessus disease in 1. Indications for pneumonectomy included multiple cavities in one lung and destruction of an entire lung. The bronchial stump was covered with a latissimus dorsi muscle flap in 7 patients and with an intercostal pedicle flap in 2.

Results

Operating time ranged from 142 to 477 minutes (median, 360 minutes). The median intraoperative blood loss was 555 mL (range, 130 to 1,245 mL). There was no operative mortality. Bronchopleural fistula occurred in 3 patients. All fistulas were observed after right pneumonectomy, and were treated by reclosure of the bronchus. Empyema occurred in 1 patient, who was treated with irrigation. All patients achieved sputum-negative status after surgery. Two late deaths occurred. One patient died of respiratory failure 11 months after surgery. A second patient, the only patient who had recurrent disease, died of respiratory failure 4 years postoperatively.

Conclusions

Despite bronchial stump protection, right pneumonectomy carries a risk for bronchopleural fistula. Nonetheless, pneumonectomy can result in high cure rates in patients with nontuberculous mycobacterial infections.     

Successful management of two heart transplant recipients with mycobacterial pulmonary infections

We report two cases of pulmonary tuberculosis in heart transplant recipients: a 46-year-old man with pulmonary tuberculosis due to Mycobacterium tuberculosis and a 64-year-old man with nontuberculous mycobacterial infection with pulmonary infiltrates due to Mycobacterium xenopi. The time intervals from transplantation to diagnosis were 3 and 4 years, respectively. The patient with tuberculosis underwent standard treatment with isoniazid, rifampin, ethambutol, and pyrazinamide. The patient with the nontuberculous mycobacterial infection received treatment with clarithromycin and ciprofloxacin for 18 months in addition to rifampin for the first 3 months. Both patients responded well to treatment. No recurrences were observed during follow-up. The interactions between antibiotic treatment and cyclosporine therapy should be observed closely in organ transplant recipients, requiring frequent level determinations and dosing changes.     

Acute empyema with intractable pneumothorax associated with ruptured lung abscess caused by <Emphasis Type="Italic">Mycobacterium avium</Emphasis>

Nontuberculous mycobacterial lung disease rarely features pleural involvement. Therapeutic strategies for this situation have not been well established. We present a case of acute empyema with intractable pneumothorax associated with ruptured lung abscess caused by Mycobacterium avium in an immunocompromised patient. Combined treatment that included multidrug antibiotic therapy and nonresectional surgery resulted in a good outcome.     

Non-tuberculous pulmonary infections in Scotland: a cluster in Lothian?

BACKGROUND--A retrospective study was carried out to confirm the clinical impression that, in Lothian, non-tuberculous mycobacterial infections are as common as pulmonary tuberculosis. METHODS--All pulmonary isolates of Mycobacterium tuberculosis/bovis and non-tuberculous mycobacteria in Scotland from April 1990 to March 1993, and the notes of all patients with M malmoense isolates in Lothian, were reviewed. Information on mycobacterial culture procedures in Scottish laboratories was obtained as part of an audit project. RESULTS--Of all pulmonary isolates of mycobacteria in Lothian 53% (108/205) were non-tuberculous strains compared with 18% (140/800) for Scotland outside Lothian. Although comparable in population size and laboratory techniques, Lothian (108) had almost twice as many isolates of non-tuberculous mycobacteria as Glasgow (56), but the proportions of M malmoense and M avium intracellulare complex were similar in both areas. Of 41 patients with M malmoense isolates in Lothian 30 (75%) had clinically significant lung disease; only one was HIV positive. CONCLUSIONS--Non-tuberculous mycobacteria pose an increasing clinical problem in Scotland as a cause of pulmonary disease. There is a cluster of cases with M malmoense infection in Lothian which cannot be attributed to the high local prevalence of HIV.     

Antibody response against Mycobacterium avium complex in cystic fibrosis patients measured by a novel IgG ELISA test

BackgroundEarly signs of Mycobacterium avium complex pulmonary disease can be missed in patients with cystic fibrosis due to subclinical infection or delays in mycobacterial culture. The aim of this study was to determine the diagnostic accuracy of a novel enzyme linked immunosorbent assay for immunoglobulin G against Mycobacterium avium complex, which could help stratify patients according to risk.MethodsA retrospective cross sectional analysis of serum samples from the Copenhagen Cystic Fibrosis Center was performed. Corresponding clinical data were reviewed and patients with cystic fibrosis were assigned to one of four groups based on their mycobacterial culture results. In addition, anti-Mycobacterium avium complex immunoglobulin G levels were measured longitudinally before and after first positive culture in the period 1984–2015.ResultsThree-hundred and five patients with cystic fibrosis were included with a median of five nontuberculous mycobacterial cultures. Four individuals had Mycobacterium avium complex pulmonary disease at the time of cross sectional testing and their median antibody level was 22-fold higher than patients with no history of infection (1820 vs. 80 IgG units; p < 0.001). Test sensitivity was 100% (95% CI 40–100) and specificity 77% (95% CI 72–81). Longitudinal kinetics showed rising antibodies prior to first positive culture suggesting diagnostic delay.ConclusionsAntibody screening for Mycobacterium avium complex may be used as a supplement to culture. Although confirmation in a larger cohort is needed, our findings suggest that stratifying a cystic fibrosis population into high- and low-risk groups based on antibody levels may help clinicians identify patients in need of more frequent culture.     

Mycobacterial infection in HIV seropositive and seronegative populations, 1987-93.

BACKGROUND--Although the causes of the worldwide resurgence of tuberculosis are multifactorial, the HIV epidemic is believed to have had a central role. Control is further threatened by the emergence of multidrug-resistant tuberculosis. METHODS--A retrospective evaluation was undertaken of trends in pulmonary and extrapulmonary culture positive mycobacterial pathology, and the prevalence of drug-resistant tuberculosis in both HIV seropositive and, presumptively, HIV seronegative patients receiving their clinical care at St Mary's Hospital, London. Five hundred and thirty eight patients (188 of whom were known to be HIV seropositive) with positive mycobacterial isolates between January 1987 and March 1993 were identified from laboratory records. These were cross referenced with drug surveillance records. RESULTS--Overall, between 1987 and 1992 there was a progressive 3.5 fold increase in positive mycobacterial isolates and a 2.5 fold increase in patients with proven mycobacterial infection. This increase was greater within the HIV seropositive population. A total of 663 positive mycobacterial isolates was evaluated; the major pathogen identified was Mycobacterium tuberculosis (379 isolates, 57%). Three hundred and fourteen patients were diagnosed as having M tuberculosis, 49 of whom were HIV seropositive. M tuberculosis was predominantly isolated from the lung. Of 358 positive cultures for M tuberculosis (68 HIV seropositive, 290 presumptively HIV seronegative), only 27 isolates (7.6%), almost exclusively derived from presumed HIV seronegative patients, were resistant to either isoniazid, rifampicin, or both drugs together. No increases in drug-resistant isolates were observed over this period. CONCLUSIONS--There has been a considerable increase in the incidence of tuberculosis in both HIV seronegative and seropositive populations during the study period. The emergence of drug-resistant tuberculosis was not observed.     

Completion pneumonectomy for chronic mycobacterial disease

OBJECTIVE: Patients with persistent pulmonary infections from mycobacterial disease present a difficult clinical challenge. These individuals typically have poor pulmonary function, malnutrition, and other comorbidities, and few guidelines exist regarding optimal therapy. We report our experience with completion pneumonectomy as part of a multidisciplinary treatment program for patients with recurrent, persistent mycobacterial disease. METHODS: During a 9-year period, 26 consecutive patients underwent completion pneumonectomy for mycobacterial disease. All patients underwent intensive, guided preoperative antibiotic therapy and aggressive nutritional supplementation. Complete surgical resection of the remaining destroyed or infected lung tissue was performed, often through an extrapleural dissection with intrapericardial ligation of vessels. Vascularized tissue flaps were used whenever possible to buttress the bronchial stump closure. Postoperative management consisted of a multidisciplinary approach, with ongoing antibiotic and nutritional therapy. RESULTS: The primary organisms were Mycobacterium avium complex (n = 15), Mycobacterium tuberculosis (n = 5), Mycobacterium abscessus (n = 3), Mycobacterium xenopi (n = 2), and Mycobacterium chelonae (n = 1). Operative mortality was 23% (6/26): respiratory failure or adult respiratory distress syndrome in 2 cases, sepsis in 2, bronchopleural fistula in 1, and pulmonary embolism in 1. Significant morbidity occurred in 46% (12/26). Among the 17 long-term survivors, sputum conversion or discontinuation of medications was achieved in 14 (82%). Mean length of follow-up was 45 months (range 4-105 months). CONCLUSION: Completion pneumonectomy remains an important component of therapy in patients with mycobacterial disease who have had failure of previous therapy. Although associated with significant risks, successful outcomes can be achieved with an organized, multidisciplinary approach and careful postoperative follow-up.     

Tuberculosis of the Ankle in a Non-immunocompromised Male: A Case Report and Review of the Literature

The prevalence and incidence of tuberculosis has declined rapidly in Western Europe during the last century, although a slight increase is being seen due to immigration from countries where tuberculosis is still a common disease. We present a very rare case of primary ankle tuberculosis in a 51-year-old native German male without any risk factors or prior lung manifestation. A delay in diagnosis and treatment when a patient presents with ankle arthritis caused by Mycobacterium tuberculosis should make one aware of the possibility of primary joint tuberculosis, which is extremely unusual and it can mimic various other joint diseases. If the diagnosis is in doubt, early biopsy should be mandatory.     

Nontuberculous mycobacterial peritonitis in peritoneal dialysis patients

While nontuberculous mycobacterial peritonitis is uncommon among peritoneal dialysis (PD) patients, these infections have serious consequences. They present a significant diagnostic and therapeutic challenge for clinicians. Diagnosis can be delayed due to the slow growth rate of some mycobacterial species. These organisms can also be overlooked when adequate culture media are not used in the microbiological evaluation process. The choice of antimicrobial therapy depends upon isolation and speciation of the infecting Mycobacterium species, and prompt catheter removal is essential. Because serious intra-abdominal complications may follow infection, identifying patient risk factors for nontuberculous mycobacterial peritonitis and initiating prompt diagnosis and treatment are essential. We report three cases of peritonitis associated with Mycobacterium chelonae and Mycobacterium gordonae, each with a unique presentation, and discuss the appropriate diagnosis and treatment strategies for the management of PD-associated mycobacterial infections.     

Infection with Mycobacterium abscessus after Mohs Micrographic Surgery in an Immunocompetent Patient

Background Nontuberculous mycobacterial infections are increasing in incidence. They have been reported following multiple procedures, including dialysis, liposuction, soft tissue augmentation, pedicures, public baths, acupuncture, placement of contaminated foreign devices such as the Norplant (Wyeth Pharmaceuticals, Collegetown, PA, USA), intravenous catheters, and during surgery from contamination of medical instruments.
Objective We report a case of Mycobacterium abscessus infection presenting as erythematous papules occurring after Mohs micrographic surgery. We also review the literature on nontuberculous mycobacterial infection to discuss common presentations, diagnosis, and treatment options.
Methods/Materials One case presenting to an outpatient dermatology surgery clinic is presented with extensive review of the medical literature on M. abscessus.
Results/Conclusion Infection with nontuberculous mycobacteria can present with varied nonspecific morphologies. A high degree of clinical suspicion is necessary to avoid delays in diagnosis and treatment.     

Treatment of neuro-ophthalmologic manifestations of tuberculosis

Opinion statement In the absence of obvious pulmonary or disseminated tuberculosis, ocular and central nervous system (CNS) tuberculosis may represent a significant diagnostic challenge. Refinements in polymerase chain reaction techniques and neuroimaging have strengthened the battery of tests used to diagnose CNS and ocular tuberculosis, yet in many cases, the diagnosis remains one of exclusion; it may ultimately be determined through exacerbation by anti-inflammatory therapy with subsequent improvement by antitubercular medication treatment. Because of emerging drug resistance, at least a two-drug regimen is required for therapeutic testing and treatment of isolated ocular tuberculosis. If pulmonary or miliary disease coexists, a 6-month, four-drug regimen with isoniazid, rifampin, pyrazinamide, and ethambutol is required for treatment. Tubercular meningitis is treated with the same four-drug regimen for at least 9 to 12 months. Burden of therapeutic compliance rests on the treating physician and public health sector. Best compliance is realized with directly observed therapy.     

Drug-resistant pulmonary tuberculosis in a cohort of southern African goldminers with a high prevalence of HIV infection.

OBJECTIVES: To determine rates of drug resistance to Mycobacterium tuberculosis and associated risk factors, including HIV infection. DESIGN: Prospective cohort study of patients with pulmonary tuberculosis. SETTING: The study population comprised 28,522 men working on four goldmines in Westonaria, Gauteng. Health care is provided at a 240-bed mine hospital, Gold Fields West Hospital, and its primary health care facilities. SUBJECTS: All 425 patients with culture-positive pulmonary tuberculosis identified in 1995. OUTCOME MEASURES: Tuberculosis drug resistance on enrollment and after 6 months' treatment. RESULTS: There were 292 cases of new tuberculosis, 77 of recurrent disease and 56 prevalent cases in treatment failure. Two hundred and seven patients (48.7%) were HIV infected. Primary resistance to one or more drugs (9%) was similar to the 11% found in a previous study done on goldminers in 1989. Primary multidrug resistance (0.3%) was also similar (0.8%). Acquired multidrug resistance was 18.1%: 6.5% for recurrent disease and 33.9% in treatment failure cases. Neither HIV infection nor the degree of immunosuppression as assessed by CD4+ lymphocyte counts was associated with drug resistance at the start or end of treatment. New patterns of drug resistance were present in 9 of 52 patients in treatment failure at 6 months, 1 of whom was HIV-infected. CONCLUSION: Primary and acquired drug resistance rates are stable in this population and are not affected by the high prevalence of HIV infection.     

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.     

Management of infections due to nontuberculous mycobacteria in solid organ transplant recipients—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the epidemiology, diagnosis, prevention, and management of nontuberculous mycobacterial infections in the pre‐ and post‐transplant period. NTM commonly cause one of five different clinical syndromes: pleuropulmonary disease, skin and soft tissue infection, osteoarticular infection, disseminated disease, including that caused by catheter‐associated infection, and lymphadenitis. Diagnosis of these infections can be challenging, particularly when they are isolated from nonsterile spaces, owing to their ubiquity in nature. Consequently, diagnosis of pulmonary infections with these pathogens requires fulfillment of microbiologic, radiographic, and clinical criteria to address this concern. A combination of culture and molecular diagnostic techniques is often required to make a species‐level identification. Treatment varies depending on the species isolated and is complex, owing to drug toxicities, need for long‐term multidrug regimens, and consideration of complex drug‐drug interactions between antimicrobials and immunosuppressive agents. Given these treatment challenges, efforts should be made in both the hospital and community settings to limit exposure to these pathogens to the extent feasible.     

Ultrashort-course chemotherapy for culture-negative pulmonary tuberculosis--a qualified success

A group of 250 patients with new or enlarging apical lung lesions which were thought to be tuberculous, and who had positive tuberculin tests but negative sputum smears and cultures for Mycobacterium tuberculosis, were treated with an ultrashort (3-month), 4-drug (rifampicin, isoniazid, pyrazinamide and ethambutol) regimen. One patient developed bacteriologically positive pulmonary tuberculosis (PTB) during the treatment period and 35 others (14%) developed bacteriologically positive PTB after completing the drug regimen.     

A large nontuberculous mycobacterial granuloma mimicking lung cancer; report of a case

A 45-year-old woman with no immunodeficiency or clinical symptoms presented to our hospital for treatment of an enlarging spherical lung tumor in 4.0-cm-diameter. Chest radiography 8 years ago had shown a 1.5-cm-diameter tumor. Chest computed tomography (CT) showed the solitary tumor, located in the right apical segment, to have an irregular margin without satellite lesions or cavitations. Mycobacterium avium complex (MAC) was cultured in tumor specimens incised during transbronchial biopsy. Right upper lobectomy was performed because of resistance to 6-month antituberculosis treatment. Pathological findings showed a MAC-infected granuloma with caseous necrosis. Postoperative course was uneventful and she had no recurrence 3 years after surgery. These findings suggest that nontuberculous mycobacterial granuloma can enlarge without clinical manifestations or any satellite lesions and cavitations, leading to a misdiagnosis of lung cancer.     

Pulmonary tuberculosis among political asylum seekers screened at Heathrow Airport, London, 1995-9

BACKGROUND: Over 50% of cases of tuberculosis (TB) in the UK occur in people born overseas, and new entrants to the country are screened for TB. A study was undertaken to determine the prevalence and disease characteristics of pulmonary TB in new entrants to the UK seeking political asylum. METHODS: A retrospective analysis of the results of screening 53 911 political asylum seekers arriving at Heathrow Airport between 1995 and 1999 was performed by studying Airport Health Control Unit records and hospital medical records. Outcome measures were chest radiograph abnormalities, sputum smear, culture, and drug resistance data for Mycobacterium tuberculosis. RESULTS: The overall prevalence of active TB in political asylum seekers was 241 per 100 000. There were large variations in prevalences of TB between asylum seekers from different regions, with low rates from the Middle East and high rates from the Indian subcontinent and sub-Saharan Africa. The frequency of drug resistance was high; 22.6% of culture positive cases were isoniazid resistant, 7.5% were multidrug resistant (resistant to both isoniazid and rifampicin), and 4% of cases diagnosed with active disease had multidrug resistant TB. CONCLUSIONS: The prevalence rate of TB in political asylum seekers entering the UK through Heathrow Airport is high and more M tuberculosis isolates from asylum seekers are drug resistant than in the UK population. Extrapolating these figures, it is estimated that 101 political asylum seekers with active pulmonary TB enter the UK every year, of whom about 25 would have smear positive disease.     

Identification of HIV patients with active pulmonary tuberculosis using urine based polymerase chain reaction assay

BACKGROUND: Despite the increased dissemination of tuberculosis among HIV infected patients, the diagnosis is difficult to establish. Traditional microbiological methods lack satisfactory sensitivity. We have developed a highly sensitive and specific nested polymerase chain reaction (PCR) capable of detecting Mycobacterium tuberculosis DNA in urine specimens and have used this test to examine urine specimens from HIV patients with active pulmonary tuberculosis. METHODS: Urine specimens from 13 HIV infected patients with microbiologically proven active pulmonary tuberculosis, 10 AIDS patients with non-tuberculous mycobacterial infection (documented by blood culture), 53 AIDS patients with no evidence of mycobacterial disease, and 80 healthy subjects (25 with positive skin test to purified protein derivative) were tested for M tuberculosis using PCR, acid fast staining (AFS), and culture. RESULTS: Of the urine specimens from patients with active tuberculosis, all tested positive by PCR, two by culture, and none by AFS. No reactivity was observed in urine specimens from patients with non-tuberculous mycobacterial infection. Of the 53 AIDS patients without mycobacterial infection, one had a positive urine PCR. Normal subjects were all negative. CONCLUSIONS: Urine based nested PCR for M tuberculosis may be a useful test for identifying HIV patients with pulmonary tuberculosis.