Massive and Lengthy Clonal Nosocomial Expansion of Mycobacterium abscessus subsp. massiliense among Patients Who Are Ventilator Dependent without Cystic Fibrosis.

Nontuberculous mycobacterial infections are generally believed to be independently acquired from the environment. Although person-to-person transmission of nontuberculous mycobacteria, especially Mycobacterium abscessus subsp. massiliense, is a serious concern among individuals with cystic fibrosis (CF), evidence of its spread among patients without CF has never been established. We unexpectedly found a number of M. abscessus subsp. massiliense cases among patients without CF in a hospital. This study aimed to define the mechanism of M. abscessus subsp. massiliense infection among patients who were ventilator dependent and without CF who had progressive neurodegenerative diseases in our long-term care wards from 2014 to 2018 during suspected nosocomial outbreaks. We conducted whole-genome sequencing of M. abscessus subsp. massiliense isolates from 52 patients and environmental samples. Potential opportunities for in-hospital transmission were analyzed using epidemiological data. M. abscessus subsp. massiliense was isolated from one air sample obtained near a patient without CF who was colonized with M. abscessus subsp. massiliense but not from other potential sources. Phylogenetic analysis of the strains from these patients and the environmental isolate revealed clonal expansion of near-identical M. abscessus subsp. massiliense isolates, with the isolates generally differing by fewer than 22 single nucleotide polymorphisms (SNPs). Approximately half of the isolates differed by fewer than nine SNPs, indicating interpatient transmission. Whole-genome sequencing revealed a potential nosocomial outbreak among patients who were ventilator dependent and without CF. IMPORTANCE The isolation of M. abscessus subsp. massiliense from the air, but not from environmental fluid samples, may suggest airborne transmission. This was the first report to demonstrate person-to-person transmission of M. abscessus subsp. massiliense, even among patients without CF. M. abscessus subsp. massiliense may spread among patients who are ventilator dependent without CF through direct or indirect in-hospital transmission. The current infection control measures should address potential transmission among patients without CF, particularly in facilities that treat patients who are ventilator dependent and patients with preexisting chronic pulmonary diseases, such as CF.

Association between sputum conversion and in-hospital mortality in elderly patients with pulmonary tuberculosis: a retrospective study.

BACKGROUND: Non-conversion of sputum culture or smear within 2 months after the start of treatment is a known poor prognostic factor of pulmonary tuberculosis. In elderly patients, sputum conversion may be delayed because of the age-related decline in immune competence. This study aimed to assess how a long interval to sputum conversion predicts in-hospital mortality in elderly patients with pulmonary tuberculosis. METHODS: Consecutive elderly patients (age > 65 years) who were admitted to our institution for bacteriologically confirmed pulmonary tuberculosis were included. The association between sputum conversion within 30, 60, 90, or 120 days from the start of treatment and in-hospital mortality were analyzed by Cox proportional-hazards regression after adjustment for other potential variables. RESULTS: This study included 262 patients, and 74 patients (28%) died during hospitalization. Multivariate analyses showed that sputum non-conversion within 90 days (adjusted hazard ratio 0.424, 95% CI 0.252-0.712, p = 0.001) or 120 days (0.333, 0.195-0.570, p < 0.001) was independently associated with in-hospital mortality, whereas that within 60 days was not (p = 0.890). CONCLUSIONS: In elderly patients with tuberculosis, 2 months may be insufficient when evaluating sputum conversion as a prognostic factor. Sputum non-conversion within 90 days or longer may predict in-hospital mortality more accurately.

Comparison of chest computed tomography features between pulmonary tuberculosis patients with culture-positive and culture-negative sputum for non-mycobacteria: A retrospective observational study.

ABSTRACT: Although complication with non-mycobacterial pneumonia among patients with pulmonary tuberculosis (TB) may lead to poor prognosis, discrimination between TB complicated with and without non-mycobacterial pneumonia using radiological imaging has not been fully elucidated. We aimed to clarify the differences in chest computed tomography (CT) features between pulmonary TB patients with culture-positive and culture-negative sputum for non-mycobacteria.We retrospectively included consecutive patients admitted to our hospital from January 2013 to December 2015 for bacteriologically-confirmed pulmonary TB, who were tested by sputum culture for non-mycobacteria, and who underwent chest CT within 2 weeks before or after admission. Chest CT features were compared between pulmonary TB patients who had positive non-mycobacterial cultures and in those who had not.Of 202 patients with pulmonary TB, 186 (92%) were tested by sputum culture for non-mycobacteria and underwent chest CT. Among these, non-mycobacteria were isolated in 118 patients (63%), while 68 patients (37%) had negative cultures. Patients with a positive culture for non-mycobacteria were significantly older and had lower levels of physical activity and albumin, higher levels of C-reactive protein, and a greater number of respiratory failures. By CT, emphysematous lesions, ground-glass opacities, airspace consolidation, air-bronchogram, interlobular septal thickening, bronchiectasis, pleural effusion, pleural thickening, and lymph node enlargement were more frequently in patients with a positive culture for non-mycobacteria. These chest CT features could be helpful for detecting complication with non-mycobacterial pneumonia in patients with pulmonary TB.

Quantitative assessment of the association between erector spinae muscle and in-hospital mortality in elderly patients with pulmonary tuberculosis.

OBJECTIVE: Skeletal muscle size is considered a predictor of prognosis in patients with respiratory diseases including Mycobacterium avium complex lung disease. However, no research focused on its impact on prognosis in patients with pulmonary tuberculosis (TB). Thus, this study aimed to assess the association between erector spinae muscle (ESM) size and in-hospital mortality among patients with pulmonary TB. RESULTS: We retrospectively included 258 consecutive patients aged over 65 years old, who were admitted to the hospital for bacteriologically confirmed pulmonary TB, and all underwent chest computed tomography (CT) scan upon admission. The cross-sectional area of the ESM (ESMcsa) was measured at the lower margin of the 12th thoracic vertebra on a single-slice CT scan image and was adjusted according to body surface area (BSA). In total, 71 (28%) patients died during hospitalization. The non-survivor group had a high incidence of respiratory failure and comorbidities and lower hemoglobin and albumin levels, performance status score, and ESMcsa/BSA. Multivariate analysis revealed that low performance status score and hemoglobin and albumin levels, but not ESMcsa/BSA and body mass index, could independently predict in-hospital mortality after adjusting for age and comorbidities. Therefore, ESM size was not associated with in-hospital mortality in patients with pulmonary TB.

A solitary pulmonary nodule caused by Mycobacterium tuberculosis var. BCG after intravesical BCG treatment: a case report.

BACKGROUND: Intravesical instillation of bacillus Calmette-Guérin (BCG) as a treatment for superficial bladder cancer rarely causes pulmonary complications. While published cases have been pathologically characterized by multiple granulomatous lesions due to disseminated infection, no case presenting as a solitary pulmonary nodule has been reported. CASE PRESENTATION: A man in his 70 s was treated with intravesical BCG for early-stage bladder cancer. After 1 year, he complained of productive cough with a solitary pulmonary nodule at the left lower lobe of his lung being detected upon chest radiography. His sputum culture result came back positive, with conventional polymerase chain reaction (PCR) identifying Mycobacterium tuberculosis complex. However, tuberculosis antigen-specific interferon-gamma release assay came back negative. Considering a history of intravesical BCG treatment, multiplex PCR was conducted, revealing the strain to be Mycobacterium tuberculosis var. BCG. The patient was then treated with isoniazid, ethambutol, levofloxacin, and para-aminosalicylic acid following an antibiotic susceptibility test showing pyrazinamide resistance, after which the size of nodule gradually decreased. CONCLUSION: This case highlights the rare albeit potential radiographic presentation of Mycobacterium tuberculosis var. BCG, showing a solitary pulmonary nodule but not multiple granulomatous lesions, after intravesical BCG treatment. Differentiating Mycobacterium tuberculosis var. BCG from Mycobacterium tuberculosis var. tuberculosis is crucial to determine whether intravesical BCG treatment could be continued for patients with bladder cancer.

Efficacy and safety of fluoroquinolone-containing regimens in treating pulmonary Mycobacterium avium complex disease: A propensity score analysis.

BACKGROUND: Although combination therapy using clarithromycin, rifampicin, and ethambutol is recommended for patients with pulmonary Mycobacterium avium complex (MAC) disease, some patients do not tolerate it because of adverse effects or underlying diseases. The efficacy and safety of fluoroquinolone-containing combination regimens as an alternative remain uncertain. This study aimed to compare the efficacy and safety of fluoroquinolone-containing regimens with those of the standard regimens for treating pulmonary MAC disease. METHODS: We retrospectively included consecutive MAC patients who were treated in our hospital between January 2011 and May 2019. Patients treated with fluoroquinolone-containing regimens who had relapsed after treatment with standard regimens were excluded. A propensity score analysis was conducted to reduce selection bias, and the proportions of clinical improvement, defined by chest imaging findings and sputum conversion, were compared between the fluoroquinolone-containing regimen and standard regimen groups. RESULTS: We analyzed 28 patients who received fluoroquinolone-containing regimens and 46 who received the standard regimen. Fluoroquinolone-containing regimens were more likely selected for patients with cavitary lesions, diabetes mellitus, culture negativity, a low daily physical activity level, a decreased lymphocyte count and an increased CRP level. The propensity score was calculated using these variables (C-statistic of the area under the receiver operating characteristic curve of the propensity score: 0.807, p < 0.0001). The fluoroquinolone-containing regimens were significantly inferior to the standard regimen in clinical improvements (p = 0.002, Log-rank test) in the univariate analysis, but the significance was lost after adjusting for the propensity score (HR 0.553, 95% CI 0.285-1.074, p = 0.080). Six (21%) patients in the fluoroquinolone-containing regimen group and ten (22%) patients in the standard regimen group experienced low-grade adverse effects. CONCLUSIONS: There was no significant difference in clinical improvement between these regimens after propensity score adjustment. A large-scale prospective study is required to validate these results.

The impact of performance status on tuberculosis-related death among elderly patients with lung tuberculosis: A competing risk regression analysis.

While advanced age is a main prognostic factor in patients with tuberculosis, the factors that specifically affect tuberculosis-related death are unclear because elderly people are at a risk for other age-related lethal diseases. We aimed to assess the impact of performance status on tuberculosis-related death among elderly patients with lung tuberculosis. Elderly patients (≥65 years of age) admitted to our hospital for bacteriologically-diagnosed lung tuberculosis were included, and analyzed the influence of performance status on tuberculosis-related in-hospital death, with non-tuberculosis-related death as a competing risk. Forty and 19 of the 275 patients died from tuberculosis-related causes and non-tuberculosis-related causes, respectively. The tuberculosis-related death group had a greater number of patients with a poor performance status (defined as category 3 and 4 [HR 21.022; 95%CI 2.881-153.414; p = 0.003]), a lower serum albumin level (HR 0.179; 95%CI 0.090-0.359; p < 0.001) and a higher C-reactive protein level (HR1.076; 95%CI 1.026-1.127; p = 0.002). A multivariate competing risk regression analysis showed that a poor performance status (HR 7.311; 95%CI 1.005-53.181; p = 0.049) and low albumin level (HR 0.228; 95%CI 0.099-0.524); p = 0.001) significantly predicted tuberculosis-related death. Performance status can be a useful scale for predicting tuberculosis-related death among elderly patients with pulmonary tuberculosis.

A high C-reactive protein level and poor performance status are associated with delayed sputum conversion in elderly patients with pulmonary tuberculosis in Japan.

INTRODUCTION: Although the aging population had been increasing in many countries, the factors associated with sputum conversion in elderly patients with pulmonary tuberculosis have not been fully elucidated. OBJECTIVES: We aimed to identify the predictors of delayed sputum conversion and to assess the impact of non-conversion on mortality during tuberculosis treatment in elderly patients. METHODS: Elderly patients (>65 years) admitted at our hospital in Japan for sputum smear-positive pulmonary tuberculosis were included. The risk factors for sputum non-conversion after 2 months of treatment were determined using multiple logistic regression. Cox hazard regression was used to assess the influence of non-conversion on mortality. RESULTS: We included 185 patients, with median age of 82 years (IQR, 79-88 years). The median time to conversion was 47 (95% CI 43-51) days, and 62 (34%) were identified as non-converters. Multivariate analysis showed that high pretreatment smear grade, high C-reactive protein level and poor performance status were associated with non-conversion. Non-conversion did not contribute to death during treatment. CONCLUSIONS: In elderly patients, inflammation level and physical activity level, along with initial smear grade may have a significant impact on delayed sputum conversion. Non-conversion after two months of treatment might not be related with mortality.

Factors associated with atypical radiological findings of pulmonary tuberculosis.

BACKGROUND: Unusual radiological images may delay diagnosis of pulmonary tuberculosis. This study aimed to analyze the risk factors for an atypical radiological image in patients with pulmonary tuberculosis. METHODS: We retrospectively analyzed data from patients admitted to one hospital from January 2013 to December 2016 for sputum smear-positive lung tuberculosis who underwent chest computed tomography (CT) on admission. Patients whose sputum cultures were positive for general bacteria were excluded. Patient characteristics and laboratory data were compared between patients with cavity and those without and between patients with upper predominant lung involvement and those without. RESULTS: This study included 94 (93%) of 101 patients who underwent chest CT. The non-cavity group was older, had a greater number of females, had a lower C-reactive protein (CRP) level, and had a lower glomerular filtration rate. Multivariate analysis showed that a low CRP level (OR 0.808; 95% CI 0.674-0.967; p = 0.020) significantly predicted non-cavity pulmonary tuberculosis. The non-upper predominant lung involvement group was older and had a greater number of females, poorer performance status, a higher CRP level, and a lower serum albumin level. A poor performance status (OR 2.155; 95% CI 1.257-3.693; p = 0.005) was found to significantly predict pulmonary tuberculosis with non-upper predominant lung distributions. CONCLUSIONS: A low CRP level and poor performance status were associated with non-cavity and non-upper predominant lung distribution, respectively, in patients with pulmonary tuberculosis. Tuberculosis patients with these characteristics may present unusual chest images.

Impact of additional antibiotics on in-hospital mortality in tuberculosis isolated general bacteria: A propensity score analysis.

Whether or not additional antibiotics with anti-tuberculosis agents are required to treat bacterial co-infection with pulmonary tuberculosis is unclear. We aimed to assess the impact of additional antibiotics on mortality in pulmonary tuberculosis patients whose sputum cultures were positive for general bacteria as a surrogate definition of bacterial pneumonia. This study was a single-center retrospective cohort using a propensity score analysis. We included patients who were admitted for pulmonary tuberculosis and whose sputum cultures were positive for general bacteria. The mortality of patients who received additional antibiotics was analyzed after adjusting for other variables, including the propensity score predicting treatment with additional antibiotics. We assessed 68 and 55 tuberculosis patients treated with and without general antibiotics, respectively. Additional antibiotics tended to be administered to patients with a high level of C-reactive protein and neutrophil count, poor performance status, hypoxemia and hypoalbuminemia (C-statistics of area under receiver operating characteristic curve to the propensity score; 0.884, p < 0.001). In the multivariate analysis, advanced age and not the use of additional antibiotics was associated with in-hospital mortality. Additional antibiotics with anti-tuberculosis agents may not improve the prognosis of pulmonary tuberculosis patients whose sputum cultures were positive for general bacteria. Isolation of general bacteria does not equate to complication with bacterial pneumonia, so physicians should not administer general antibiotics to TB patients based solely on the results of sputum culture for general bacteria. A prospective study is needed to verify these results using a more accurate definition of pulmonary tuberculosis complicated with bacterial pneumonia.

A mini systematic review of prognostic factors in elderly patients with tuberculosis.

BACKGROUND: While advanced age has been suggested as a prognostic factor in patients with tuberculosis, the characteristics associated with a poor outcome in elderly patients have remained unclear. The aim of this systematic review was to describe the risk factors for a poor outcome in elderly patients with tuberculosis. METHODS: We identified 1255 studies published between 1919 and 2017 from the PubMed database by using combinations of the keywords "tuberculosis [Title/Abstract]" and "elderly [Title/Abstract]". Full texts of the studies that met the inclusion criteria were further evaluated by two independent investigators. RESULTS: even retrospective cohort studies were included in this systematic review. More advanced age, comorbidities, and nutritional status were likely to be prognostic factors in Taiwan (aging country) and Japan (super-aged country), while human immunodeficiency virus infection and severe tuberculosis were associated with a poor outcome in low-income countries. Two studies from Taiwan investigated the prognostic factors of tuberculosis-specific death and non-tuberculosis-specific death separately, but no significant differences were found in the factors between the two types of death. CONCLUSIONS: The prognostic factors of tuberculosis in elderly patients varied according to the income levels of the countries. The factors in Taiwan and Japan were mainly associated with host factors, irrespective of the cause of death, which may reflect senile deterioration due to old age.

[Clinical investigation of multidrug-resistant tuberculosis --investigation of inpatients in the Kyushu region between 2004 and 2009].

OBJECTIVE: To conduct a clinical investigation of patients with multidrug-resistant (MDR) tuberculosis who received either drug therapy alone or drug therapy in combination with surgery. SUBJECTS AND METHODS: A total of 56 patients with MDR tuberculosis who were admitted to hospitals of the National Hospital Organization in the Kyushu region between January 2004 and September 2009 and received drug therapy either alone or in combination with surgery were investigated. RESULTS: As surgery could not be performed in patients with advanced age or with bilateral extensive lesions, only 12 patients (21%) were able to undergo surgery. Initial drug resistance was seen in 10 patients (23%) in the drug therapy group and four patients (33%) in the combination therapy group. Underlying diseases included diabetes in 15 patients (34%) in the drug therapy group and in 6 patients (50%) in the combination therapy group. Negative conversion of the sputum culture result was observed in 43% in the drug therapy group and in 75% in the combination therapy group. The death within three years was seen in 20 patients (45%) in the drug therapy group and 1 patient (8%) in the combination therapy group. In the drug therapy group there were more cases with resistance to 5 drugs, resistance to levofloxacin (LVFX), and/or kanamycin (KM) in those who died of tuberculosis than in non-tuberculous death cases. CONCLUSION: Resistance to 5 drugs, resistance to LVFX, and resistance to KM were contributing factors of tuberculous death. Patient's operability was one of the factors associated with a good prognosis.

[Clinical features of foreign-born tuberculosis patients treated at our hospital].

INTRODUCTION: There has been an increase in the number of foreign-born tuberculosis (TB) patients residing in Japan. The purpose of this study is to clarify the clinical features of the foreign-born TB patients treated at our hospital. MATERIALS AND METHODS: This study included foreign-born TB patients treated at our hospital between 2000 and 2009. A comparison was performed with Japanese TB patients in the same age group who were treated in the same period. RESULTS: There were 44 patients (17 males and 27 females; mean age: 23.6 +/- 5.1). These patients originated from 13 different countries, 12 of which were Asian countries such as China and the Philippines, and 8 of which were WHO-designated high-burden TB countries. The period between the patient's entry into Japan and the onset of TB was less than a year for half of the cases. As compared with the Japanese patients group, the foreign patients group included a significantly higher proportion of students and a significantly large number of cases found by periodic health examination. In terms of clinical findings, no significant difference was observed in the proportion of cavitary cases (37.5%) and of smear positive cases (37.5%); however, the frequency of drug-resistant cases (30.4%) was significantly higher among the foreign patients than the Japanese patients. The cure rate was 75% among foreign-born patients, and there were no defaulters. CONCLUSION: Compared with Japanese patients with the same ages, the foreign-born TB patients treated at our hospital included a high proportion of students from high-burden TB countries who were detected by periodic health examination and a higher proportion of drug-resistant cases. The treatment outcome was satisfactory without any defaulters. Periodic mass health examinations and drug susceptibility tests are important, and careful health examination is necessary for all individuals from high-burden TB countries when they enter Japan.