Tuberculosis mortality: patient characteristics and causes

Background

Resistance among Klebsiella pneumoniae to most antibiotics is on the rise. Tigecycline has been considered as one of the few therapeutic options available to treat multidrug-resistant bacteria. We investigated the clinical and microbiological characteristics of tigecycline non-susceptible K. pneumoniae bacteremia.

Methods

Adult patients with tigecycline non-susceptible K. pneumoniae bacteremia at a medical center in Taiwan over a 3-year period were enrolled. K. pneumoniae isolates were identified by the E-test using criteria set by the US Food and Drug Administration (FDA). Data on the clinical features of patients were collected from medical records. Genes for β-lactamases, antimicrobial susceptibilities and pulsed-field gel electrophoresis (PFGE) results were determined for all isolates.

Results

Of 36 patients, 27 had nosocomial bacteremia. Overall 28-day mortality was 38.9%. The MIC₅₀ and MIC₉₀ of tigecycline were 6 and 8 mg/L, respectively. No carbapenemase was detected among the 36 isolates. Twenty isolates carried extended spectrum β-lactamases and/or DHA-1 genes. No major cluster of isolates was found among the 36 isolates by PFGE. Intensive care unit onset of tigecycline non-susceptible Klebsiella pneumoniae bacteremia was the only independent risk factor for 28-day mortality.

Conclusions

The high mortality of patients with tigecycline non-susceptible K. pneumoniae bacteremia may suggest a critical problem. Further study to identify the possible risk factors for its development and further investigation of this type of bacteremia is necessary.     

Outcome and prognostic factors for patients with non-small-cell lung cancer and severe radiation pneumonitis

PURPOSE: Radiation pneumonitis is a serious complication that develops after thoracic irradiation. The purpose of this study was to identify prognostic factors for severe radiation pneumonitis in patients with non-small-cell lung cancer. METHODS AND MATERIALS: The medical records of patients with non-small-cell lung cancer and severe radiation pneumonitis were reviewed. Variables were analyzed by univariate and stepwise multivariate analysis using the Cox regression model. RESULTS: Among the 31 patients, the mortality rate approached 50% in the first 2 months after the onset of radiation pneumonitis. The variables significantly associated with survival in the univariate analysis were tumor histologic feature, grade and extent (out-of-field or in-field) of radiation pneumonitis, oxygenation index, and serum albumin (<35 g/L or >or=35 g/L), and uric acid levels at the onset of radiation pneumonitis. Only the extent of radiation pneumonitis and serum albumin level were independently associated with survival in the multivariate analysis. CONCLUSION: The mortality rate of non-small-cell lung cancer patients with severe radiation pneumonitis is extremely high, and survival is much shorter in patients with out-of-field radiation pneumonitis or a low serum albumin level at the onset. Additional studies to investigate the factors precipitating out-of-field radiation pneumonitis should improve the management of irradiation complications.     

Disseminated tuberculosis: a 10-year experience in a medical center

Disseminated tuberculosis remains a diagnostic challenge because the presentations are nonspecific. In the current retrospective study we describe the clinical characteristics and outcome of disseminated tuberculosis. From January 1995 to December 2004, patients with culture-confirmed tuberculosis who fulfilled the criteria for disseminated tuberculosis were selected and their medical records reviewed. Their clinical isolates were genotyped. Of the 3058 patients with culture-confirmed tuberculosis, 164 (5.4%) had disseminated disease; 14.0% of patients had acquired immunodeficiency syndrome. The most common radiographic finding was miliary lung lesions (47.0%); 31.1% of patients died at the end of the study. Poor prognostic factors included hypoalbuminemia, hyperbilirubinemia, renal insufficiency, and delayed antituberculosis treatment. Clinical findings suggestive of disseminated tuberculosis were miliary lung lesions, serum ferritin >1000 microg/L, infiltrative liver disease, and adjusted calcium >2.6 mmol/L. Simultaneously performing mycobacterial culture and histopathologic examination of bone marrow biopsy was more sensitive and faster than just performing mycobacterial blood culture in diagnosing disseminated tuberculosis. Of the 64 preserved Mycobacterium tuberculosis isolates, 47 (73.4%) were clustered and 27 (42.2%) were Beijing family. Since prognosis was worse in patients with delayed treatment, a high index of suspicion is required, especially in those with clinical findings suggestive of disseminated tuberculosis.     

Inhaled Corticosteroids Increase the Risk of Pneumonia in Patients With Chronic Obstructive Pulmonary Disease: A Nationwide Cohort Study

The association of inhaled corticosteroids (ICS) and pneumonia in patients with chronic obstructive pulmonary disease (COPD) is still controversial.From the National Health Insurance Database of Taiwan, COPD cases with history of acute exacerbation (AE) were identified (COPD cohort). Time-dependent Cox regression analysis was applied to investigate the risk factors for pneumonia with COPD severity controlled by surrogate variables. Among the COPD cohort, those who continuously used ICS for more than 360 days without interruption were selected (ICS cohort). The incidence rate of pneumonia during ICS use was compared with those before ICS use and after ICS discontinuation by using pair t test.A total of 6034 and 842 cases were identified as the COPD and ICS cohorts, respectively. In the COPD cohort, recent ICS use was independently associated with pneumonia (hazard ratio: 1.06 [1.02–1.11] for per 80 mg of budesonide). Other independent risk factors included age, male, diabetes mellitus, malignancy, low income, baseline pneumonia event, and recent use of oral corticosteroids and aminophylline. In the ICS cohort, while AE rate gradually decreased, the incidence rate of pneumonia significantly increased after ICS use (from 0.10 to 0.21 event/person-year, P = 0.001).This study demonstrates the association between ICS use and pneumonia in patients with COPD and history of AE. ICS should be judiciously used in indicated COPD patients.     

Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients: A Prospective Observational Study

Despite numerous studies, there has been little progress in the use of biomarkers for predicting treatment response in patients with tuberculosis (TB).Patients with culture-confirmed pulmonary TB between 2010 and 2014 were prospectively recruited. Blood samples were taken upon diagnosis and 2 months after the start of standard anti-TB treatment. A pilot study utilizing measurement of TB-antigen-stimulated cytokines was conducted to select potential biomarkers for further testing. Outcome was defined as persistent culture positivity at 2 months into treatment.Of 167 enrolled patients, 26 had persistent culture positivity. RANTES, IL-22, MMP-8, IL-18, MIG, and Granzyme A were selected as potential biomarkers. For predicting persistent culture positivity, receiver-operating characteristics (ROC) analysis showed that initial RANTES (AUC: 0.725 [0.624–0.827]) and 2-month MMP-8 (AUC: 0.632 [0.512–0.713]) had good discriminative ability. Using a logistic regression model, low initial RANTES level (<440 pg/mL), initial smear positivity, and high 2-month MMP-8 level (>3000 pg/mL) were associated with persistent culture positivity. Low initial RANTES level and initial smear positivity had a positive predictive value of 60% (12/20) for persistent culture positivity, compared with 4% (3/75) among patients with high RANTES level and smear negativity upon diagnosis. In the 72 patients with either low RANTES/smear negativity or high RANTES/smear positivity upon diagnosis, the 2-month MMP-8 level had a positive and negative predictive value of 24 and 94%, respectively, for 2-month culture status.Aside from an initial sputum smear status, serum RANTES level at diagnosis and MMP-8 level at 2 months of treatment may be used to stratify risk for culture persistence.     

Influence of pressure control levels on the pulse pressure variations: an animal study using healthy piglets

Pulse pressure variation (PPV) is a promising predictor for volume responsiveness. However, recent studies have criticized its validity during small tidal volume (TV) ventilation. The present study evaluated the influence of pressure control level (PCL) on PPV. Six anesthetized healthy piglets simulating hemorrhagic shock underwent five stages of intravascular volume status change. Each stage comprised four cycles of PCL manipulation. In each cycle, five different PCLs were applied in random order. Among 600 arterial pressure tracings obtained during PCL manipulations, 26 tracings were excluded because of signal artifact or ectopic beats. For the remaining 574 tracings, the percentage of normal beats among total recorded beats in each tracing was 99.80% ± 0.85%. When manipulating PCL causing an abrupt change within -16 ～ +8 cmH(2)O, the PPV responded rapidly and stabilized within 60 s after manipulation. With higher increment in PCL (+12 ～ +16 cmH(2)O), it required 90 s for PPV to stabilize. Under each cycle of PCL manipulation, the PPVs are linearly correlated to the PCL (r = 0.84 ± 0.21) and TV (r = 0.83 ± 0.22). The PPV as well as the slopes of the trend lines decreased from hypovolemic stages toward hypervolemic stages. Pulse pressure variation responds rapidly to change in ventilator setting and is linearly correlated with the PCL and TV. These characteristics may have important applications in critical care to improve the interpretation of PPV in accord to different ventilator settings.     

Clinical Characteristics and Prognosis of Nontuberculous Mycobacterial Lung Disease with Different Radiographic Patterns

Rationale  

The clinical characteristics and prognostic impact of radiographic patterns of patients with nontuberculous mycobacterial lung disease (NTM-LD) are rarely evaluated.