Increased Tuberculosis Reactivation Risk in Patients Receiving Immune Checkpoint Inhibitor-Based Therapy.

OBJECTIVE: Reports of tuberculosis (TB) during anticancer treatment with immune checkpoint inhibitors (ICIs) are increasing. However, it is not clear whether the use of ICIs is a significant risk factor for TB, including reactivation or latent TB infection (LTBI). METHODS: To determine the risk of TB reactivation in patients with lung cancer who use ICIs or tyrosine kinase inhibitors (TKIs), we conducted a retrospective study using a hospital-based cancer registry. In addition, we monitored patients with cancer using ICI or TKI in a multicenter prospective study to check the incidence of LTBI. RESULTS: In the retrospective study, several demographic factors were imbalanced between the ICI and TKI groups: the ICI group was younger, had more males, exhibited more squamous cell carcinoma in histology rather than adenocarcinoma, had fewer EGFR mutations, and received more chemotherapy. Propensity score matching was used to control for confounding factors, and we found that the incidence of TB was higher among patients with lung cancer who received ICIs than among those who received TKIs (2298 vs 412 per 100 000 person-years, P = .0165). Through multivariable analysis, group (ICI vs TKI) was the independent risk factor for TB development (adjusted hazard ratio (aHR): 6.29, 95% CI, 1.23-32.09, P = .0269). In the prospective cohort, which included 72 patients receiving ICIs and 50 receiving TKIs, we found that the incidence of positive seroconversion of LTBI by interferon gamma release assay (IGRA) was significantly higher in patients receiving ICIs (18% vs 0%, aHR: 9.88, P = 0.035) under multivariable Cox regression. CONCLUSION: The use of ICIs may be linked to a higher likelihood of TB reactivation and LTBI than individuals solely receiving TKIs as anticancer therapy. Consequently, the implementation of a screening program for TB reactivation and LTBI among patients undergoing ICI treatment could prove advantageous by enabling early detection and prompt treatment of the infection.

Aerosol particle dispersion in spontaneous breathing training of oxygen delivery tracheostomized patients on prolonged mechanical ventilation.

BACKGROUND: Tracheostomized patients undergoing liberation from mechanical ventilation (MV) are exposed to the ambient environment through humidified air, potentially heightening aerosol particle dispersion. This study was designed to evaluate the patterns of aerosol dispersion during spontaneous breathing trials in such patients weaning from prolonged MV. METHODS: Particle Number Concentrations (PNC) at varying distances from tracheostomized patients in a specialized weaning unit were quantified using low-cost particle sensors, calibrated against a Condensation Particle Counter. Different oxygen delivery methods, including T-piece and collar mask both with the humidifier or with a small volume nebulizer (SVN), and simple collar mask, were employed. The PNC at various distances and across different oxygen devices were compared using the Kruskal-Wallis test. RESULTS: Of nine patients receiving prolonged MV, five underwent major surgery, and eight were successfully weaned from ventilation. PNCs at distances ranging from 30 cm to 300 cm showed no significant disparity (H(4) = 8.993, p = 0.061). However, significant differences in PNC were noted among oxygen delivery methods, with Bonferroni-adjusted pairwise comparisons highlighting differences between T-piece or collar mask with SVN and other devices. CONCLUSION: Aerosol dispersion within 300 cm of the patient was not significantly different, while the nebulization significantly enhances ambient aerosol dispersion in tracheostomized patients on prolonged MV.

Monitoring the performance of a dedicated weaning unit using risk-adjusted control charts for the weaning rate in prolonged mechanical ventilation.

BACKGROUND: Weaning rate is an important quality indicator of care for patients with prolonged mechanical ventilation (PMV). However, diverse clinical characteristics often affect the measured rate. A risk-adjusted control chart may be beneficial for assessing the quality of care. METHODS: We analyzed patients with PMV who were discharged between 2018 and 2020 from a dedicated weaning unit at a medical center. We generated a formula to estimate monthly weaning rates using multivariate logistic regression for the clinical, laboratory, and physiologic characteristics upon weaning unit admission in the first two years (Phase I). We then applied both multiplicative and additive models for adjusted p-charts, displayed in both non-segmented and segmented formats, to assess whether special cause variation existed. RESULTS: A total of 737 patients were analyzed, including 503 in Phase I and 234 in Phase II, with average weaning rates of 59.4% and 60.3%, respectively. The p-chart of crude weaning rates did not show special cause variation. Ten variables from the regression analysis were selected for the formula to predict individual weaning probability and generate estimated weaning rates in Phases I and II. For risk-adjusted p-charts, both multiplicative and additive models showed similar findings and no special cause variation. CONCLUSION: Risk-adjusted control charts generated using a combination of multivariate logistic regression and control chart-adjustment models may provide a feasible method to assess the quality of care in the setting of PMV with standard care protocols.

Automatic tube compensation for liberation from prolonged mechanical ventilation in tracheostomized patients: A retrospective analysis.

BACKGROUND: To analyze the predictability of an automatic tube compensation (ATC) screening test compared with the conventional direct liberation test performed before continuous oxygen support for MV liberation. METHODS: This retrospective study analyzed tracheostomized patients with prolonged MV in a weaning unit of a medical center in Taiwan. In March 2020, a four-day ATC test to screen patient eligibility for ventilator liberation was implemented, intended to replace the direct liberation test. We compared the predictive accuracy of these two screening methods on the relevant outcomes in the two years before and one year after the implementation of this policy. RESULTS: Of the 403 cases, 246 (61%) and 157 (39%) received direct liberation and ATC screening tests, respectively. These two groups had similar outcomes: successful weaning upon leaving the Respiratory Care Center (RCC), success on day 100 of MV, success at hospital discharge, and in-hospital survival. Receiver operating characteristic curve analysis showed that the ATC screening test had better predictive ability than the direct liberation test for RCC weaning, discharge weaning, 100-day weaning, and in-hospital survival. CONCLUSION: This closed-circuit ATC screening test before ventilator liberation is a feasible and valuable method for screening PMV patients undergoing ventilator liberation in the pandemic era. Its predictability for a comparison with the open-circuit oxygen test requires further investigation.

Safety and efficacy of vacuum bottle plus catheter for drainage of iatrogenic pneumothorax.

BACKGROUND: Iatrogenic pneumothorax is common after thoracic procedures. For patients with pneumothorax larger than 15%, simple aspiration is suggested. Although vacuum bottle plus non-tunneled catheter drainage has been performed in many institutions, its safety and efficacy remain to be assessed. METHODS: Through this prospective cohort study (NCT03724721), we evaluated the safety and efficacy of vacuum bottle plus non-tunneled catheter drainage. Patients older than 20 years old who developed post-procedural pneumothorax were enrolled. A non-tunneled catheter was placed at the intersection of the midclavicular line and the second intercostal space. A 3-way stopcock, a drainage set, and a digital pressure gauge were connected. The stopcock was manipulated to connect the pleural space to the pressure gauge for measurement of end-expiration intrapleural pressure or to the vacuum bottle for air drainage. The rate of successful drainage, the end-expiration intrapleural pressure before, during, and after the procedure and the duration of hospitalization were recorded. RESULTS: From August 2018 to February 2020, 21 patients underwent vacuum bottle plus catheter drainage (intervention group) and 31 patients received conservative treatment (control group). The end-expiration intrapleural pressure of all patients remained less than - 20 cmH2O during drainage. No procedure related complication was observed. Large pneumothorax (≥ 15%) was associated with higher risk of persistent air leak (Odds ratio 12, 95% CI 1.2-569.7). Vacuum bottle assisted air drainage yielded shorter event-free duration than that of conservative treatment (2 days vs 5 days [interquartile range 1-4 days vs 3-7 days], p < .05). Vacuum bottle assisted air drainage also help identifying patients with persistent pneumothorax and necessitate the subsequent management. The event-free duration of persistent air leak in the intervention group was also comparable with that of conservative treatment (5 days vs 5 days [interquartile range 5-8 days vs 3-7 days], p = .45). CONCLUSIONS: Vacuum bottle plus catheter drainage of iatrogenic pneumothorax is a safe and efficient procedure. It may be considered as an alternative management of stable post-procedural pneumothorax with size larger than 15%. Trial registration The study protocol was approved by the Research Ethics Committee of National Taiwan University Hospital (No. 201805105DINA) on 6th August, 2018. The first participant was enrolled on 23rd August, 2018 after Research Ethics Committee approval. This clinical trial complete registration at U.S. National Library of Medicine clinicaltrials.gov with identifier NCT03724721 and URL: https://clinicaltrials.gov/ct2/show/NCT03724721 on 30th October, 2018.

The application of ultrasound shear wave elastography in the prediction of paradoxical upgrading reaction in tuberculous lymphadenitis. a pilot study.

BACKGROUND: Paradoxical upgrading reaction (PUR) indicates the unanticipated deterioration during therapy in patients with tuberculous lymphadenitis. We investigated the diagnostic performance of the ultrasonography and shear wave elastography (SWE) in predicting the therapeutic response of peripheral tuberculous lymphadenitis. METHODS: A prospective observational study was conducted from December 2017 to August 2020. Participants diagnosed with peripheral tuberculous lymphadenitis were included for a longitudinal follow-up utilizing ultrasonography with two-dimensional SWE to record sonographic features and the maximum elasticity value (Emax). We defined PUR as the development of any worsening symptoms of the pre-existing lymphadenitis within one month after the previous ultrasonography. RESULTS: A total of 108 sonographic and SWE examinations were performed in 20 enrollees (75% woman), and their mean ( ± standard deviation) age was 49.6 ( ± 22.7) years. The area under the receiver operating characteristic curve of Emax to predict the next-month PUR was 0.906 at the cut-point of 85 kPa, with an accuracy of 87.0%, a sensitivity of 81.1% and a specificity of 87.9%. Multivariate analysis indicated that Emax > 85 kPa (OR: 24.85, 95% CI: 4.01-154.08, p < 0.001), Emax increment rate >2 kPa/month (OR: 15.14, 95% CI: 4.24-54.06, p < 0.001), and heterogeneous echogenicity (OR: 4.37, 95% CI: 1.16-16.43, p = 0.029) were independent sonographic predictors for PUR in the coming month. CONCLUSION: A high and non-declining Emax level and heterogeneous echogenicity were associated with the next-month PUR of tuberculous lymphadenitis. Ultrasonography with SWE may be a potential radiologic marker to predict the therapeutic response of tuberculous lymphadenitis.

Application of transthoracic shear-wave ultrasound elastography in lung lesions.

INTRODUCTION: Tissue stiffness information may help in the diagnosis of lung lesions. This study aimed to investigate and validate the application of transthoracic two-dimensional shear-wave ultrasound elastography in differentiating malignant from benign subpleural lung lesions. METHODS: This study involved one retrospective observational derivation cohort from January 2016 to December 2017 and one prospective observational validation cohort from December 2017 to December 2019. The inclusion criterion was radiographic evidence of pulmonary lesions. The patients were categorised into air bronchogram and hypoechoic groups based on B-mode grayscale images. The elasticity of subpleural lung lesions with acceptable shear-wave propagation was measured. Diagnoses were made on the basis of pathology, microbiological studies or following up the clinical course for at least 6 months. RESULTS: A total of 354 patients were included. Among the 121 patients in the derivation cohort, a receiver operating characteristic curve was constructed and the cut-off point to differentiate benign from malignant lesions was 65 kPa with a Youden index of 0.60 and an accuracy of 84.3%. Among the 233 patients in the validation cohort, the diagnostic performance was maintained, with a Youden index of 0.65 and an accuracy of 86.7%. Upon applying the cut-off point to the air bronchogram group, the Youden index was 0.70 and the accuracy was 85.0%. CONCLUSIONS: This study validated the application of transthoracic shear-wave ultrasound elastography for assessing lung malignancy. A cut-off point of 65 kPa is suggested for predicting lung malignancy. Furthermore, for pulmonary air bronchogram lesions with high elasticity, tissue proofing should be considered because of the high possibility of malignancy.

Changes in albuminuria during the spontaneous breathing trial: A prospective observational study.

BACKGROUND: We hypothesized urine albumin concentration may detect the early increasing cardiac load during the spontaneous breathing trial (SBT). The purpose of our study is to determine whether the changes in urine albumin concentration before and after the SBT correlate with SBT outcome. METHODS: This prospective observational study was conducted from January 2013 to September 2013. Patients receiving endotracheal tube intubation due to acute respiratory failure were included. Urine albumin concentration was measured upon admission to the intensive care unit, before and after the SBT. RESULTS: A total of 211 patients with respiratory failure were screened. Finally, 69 patients were included for analysis. Among the 69 patients received the SBT, 61 patients passed the SBT while 8 patients didn't. Urine albumin concentration upon admission was 251.00 ± 108.21 mg/g in the SBT success group and 260.87 ± 77.95 mg/g in the SBT failure group (p = 0.97). The mean percent change in urine albumin concentration during the SBT was significantly higher in the SBT failure group (+58.44%) than in the SBT success group (+13.11%) (p = 0.02). Univariable and multivariable logistic regression model showed that the difference of urine albumin concentration before and after the SBT correlated significantly with SBT failure (adjusted OR:1.04, p = 0.01). CONCLUSION: This open label pilot study demonstrates the significant association of the changes in urine albumin concentration with SBT outcome. Further study is warranted to investigate the predictive value of urine albumin concentration.

Quality gaps and priorities for improvement of healthcare service for patients with prolonged mechanical ventilation in the view of family.

BACKGROUND: Little is known about the gaps between expectation and the perception of service quality in the care setting of prolonged mechanical ventilation (MV). METHODS: We conducted this prospective study at the Respiratory Care Center (RCC) of a medical center from February 2017 to January 2018. Family members of the patients admitted to the RCC completed a questionnaire based on the SERVQUAL instrument in two sections - expectation and perception, consisting of 22 questions each in five dimensions. We analyzed the gaps between paired items, used important-performance analysis (IPA) to identify priority items for improvement, and performed multivariate logistic regression analysis. RESULTS: A total of 167 respondents participated in the survey. The average length of patient stay in the RCC was 19.4 days, and 70.7% were successfully liberated from MV. The overall mean SERVQUAL scores for the two sections were similar (4.50 ± 0.52 and 4.51 ± 0.54 for expectation and perception, respectively; p = 0.808). IPA identified four items, including one "tangible," one "reliability" and two "empathy" with an undesired expectation/perception gap indicating a priority for improvement. Multivariate logistic regression analysis showed that male respondents, patients older than 75 years, tracheostomy, and the need for physical training or dialysis were associated with an increased gap in these priority items. CONCLUSION: Gaps exist between expectation and perception in multiple dimensions of the quality of healthcare service in the care setting of prolonged MV, indicating unmet needs and priorities for improvement.

Burden of asthma and COPD overlap (ACO) in Taiwan: a nationwide population-based study.

BACKGROUND: Patients with symptoms of both asthma and chronic obstructive pulmonary disease (COPD) may be classified with the term asthma-COPD overlap (ACO). ACO is of considerable interest as it is currently poorly characterised and has been associated with worse health outcomes and higher healthcare costs compared with COPD or asthma alone. Patients with ACO in Asia remain poorly described, and there is limited information regarding their resource utilisation compared with patients with asthma or COPD only. This study investigated the characteristics, disease burden and medical resource utilisation of patients with ACO in Taiwan. METHODS: This was a retrospective cohort study of patients identified from National Health Insurance (NHI) claims data in Taiwan in 2009-2011. Patients were classified into incident ACO, COPD or asthma cohorts according to International Classification of Disease, ninth revision, clinical modification codes in claims. Eligible patients were ≥40 years of age with 12 months' continuous enrolment in the NHI programme pre- and post-index date (date of the first relevant medical claim). RESULTS: Patients with ACO (N = 22,328) and COPD (N = 69,648) were older and more likely to be male than those with asthma (N = 50,293). Patients with ACO had more comorbidities and exacerbations, with higher medication use: short-acting ß2-agonist prescriptions ranged from 30.4% of patients (asthma cohort) to 43.6% (ACO cohort), and inhaled corticosteroid/long-acting ß2-agonist combination prescriptions ranged from 11.1% (COPD cohort) to 35.0% (ACO cohort) in the 12 months following index. Patients with ACO generally had the highest medication costs of any cohort (long-acting muscarinic antagonist costs ranged from $227/patient [asthma cohort] to $349/patient [ACO cohort]); they also experienced more respiratory-related hospital visits than patients with asthma or COPD (mean outpatient/inpatient visits per patient post-index: 9.1/1.9 [ACO cohort] vs 5.7/1.4 [asthma cohort] and 6.4/1.7 [COPD cohort]). CONCLUSIONS: Patients with ACO in Taiwan experience a greater disease burden with greater healthcare resource utilisation, and higher costs, than patients with asthma or COPD alone.

Tuberculosis mortality: patient characteristics and causes.

BACKGROUND: In the antibiotic era, tuberculosis (TB) still causes a substantial number of mortalities. We aimed to identify the causes and risks of death among TB patients. METHODS: Medical records of mortality cases of culture-proven TB diagnosed during 2003-2007 were reviewed. All TB deaths were classified into 2 groups (TB-related and non-TB-related), based on the underlying cause of death. RESULTS: During the study period, 2016 cases (male: 71.1%) of culture-proven TB were identified. The mean age was 59.3 (range: 0.3-96) years. The overall mortality rate was 12.3% (249 cases) and the mean age at death was 74 years; 17.3% (43 cases) of all TB deaths were TB-related. Most of the TB-related deaths occurred early (median survival: 20 days), and the patient died of septic shock. Malignancy, liver cirrhosis, renal failure, and miliary and pneumonic radiographic patterns were all independent predictors for all TB deaths. Cavitary, miliary and pneumonic radiographic patterns were all significant predictive factors for TB-related death. Extrapulmonary involvement and liver cirrhosis were also factors contributing to TB-related death. CONCLUSIONS: The majority of TB deaths were ascribed to non-TB-related causes. Managing TB as well as underlying comorbidities in a multidisciplinary approach is essential to improve the outcome of patients in an aging population. However, the clinical manifestations of patients with TB-related death vary; many progressed to fulminant septic shock requiring timely recognition with prompt treatment to prevent early death.

Persistent inflammation and lymphopenia and weaning outcomes of patients with prolonged mechanical ventilation.

BACKGROUND: Weaning outcomes of patients receiving mechanical ventilation (MV) are affected by multiple factors. A clinical feature of critically ill patients is the presence of lymphopenia, however the clinical significance of lymphopenia in patients receiving prolonged MV remains unclear. METHODS: We enrolled patients who received at least 21 consecutive days of MV in a medical center in Taiwan between 2007 and 2016. Patients with and without lymphopenia (mean count <1000/µL) were compared after propensity score matching. RESULTS: Of the 3460 patients included in the analysis, 1625 (47.0%) were liberated from MV within 100 days. Lymphopenia and severe lymphopenia (mean count <500/µL) during the first 21 days of MV were common (52.9% and 14.5%, respectively), and restricted cubic spline analysis showed a significant reduction in weaning success when the lymphocyte count dropped below 1000/µL. After propensity score matching, the patients with lymphopenia during the third week had a lower rate of weaning success within 100 days (p = 0.005) and a higher in-hospital mortality rate (p = 0.001) than those without lymphopenia. The lymphopenia group also had significantly reduced platelet (p < 0.001) and albumin (p < 0.001) levels. CONCLUSIONS: Our findings suggest that lymphopenia during the first 3 weeks may be a marker of poor weaning outcomes in patients with prolonged MV.

Prognostic value of plasma N-terminal pro B-type natriuretic peptide levels in pneumonia patients requiring intensive care unit admission.

BACKGROUND AND OBJECTIVE: Correct and early risk stratification for critically ill pneumonia patients remains an unmet medical need. This study aimed to test whether N-terminal pro B-type natriuretic peptide (NT-proBNP) can serve as a prognostic marker in this setting. METHODS: This prospective study enrolled 216 pneumonia patients admitted to intensive care unit. Plasma NT-proBNP samples were obtained upon admission and primary outcome was all-cause mortality at 30 days. Meanwhile, Acute Physiology and Chronic Health Evaluation (APACHE) II and Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) 2007 minor criteria were assessed. RESULTS: Overall 30-day mortality was 30%. NT-proBNP levels were significantly higher in nonsurvivors than survivors (11 938 ± 13 121 vs 5658 ± 9240 pg/mL, P = 0.001). Area under receiver operating characteristic curves of NT-proBNP, APACHE II and IDSA/ATS 2007 minor criteria were not significantly different regarding prediction of mortality (0.715, 0.754 vs 0.654, P = 0.085). Adding NT-proBNP to APACHE II significantly increased the area under receiver operating characteristic curve from 0.754 to 0.794 (P = 0.048). Receiver operating characteristic analysis revealed optimal NT-proBNP and APACHE II cut-offs of 2177.5 pg/mL and 25.5, respectively. In multivariate analysis, both NT-proBNP and APACHE II values above cut-offs had a significantly higher probability of death than those below cut-offs. A categorical approach combining NT-proBNP and APACHE II cut-offs provides additional risk stratification over a single marker approach. CONCLUSIONS: For pneumonia patients admitted to intensive care unit, NT-proBNP strongly and independently predicts mortality, and its prognostic accuracy is comparable with APACHE II and IDSA/ATS 2007 minor criteria.

Revisiting tuberculous pleurisy: pleural fluid characteristics and diagnostic yield of mycobacterial culture in an endemic area.

BACKGROUND: Tuberculous pleurisy is traditionally indicated by extreme lymphocytosis in pleural fluid and low yield of effusion culture. However, there is considerable inconsistency among previous study results. In addition, these data should be updated due to early effusion studies and advances in culture methods. METHODS: From January 2004 to June 2009, patients with tuberculous pleurisy were retrospectively identified from the mycobacteriology laboratories and the pathology and tuberculosis registration databases of two hospitals in Taiwan where tuberculosis is endemic. Pleural fluid characteristics and yields of mycobacterial cultures using liquid media were evaluated. RESULTS: A total of 382 patients with tuberculous pleurisy were identified. The median lymphocyte percentage of total cells in pleural fluids was 84% (IQR 64-95%) and 17% of cases had a lymphocyte percentage of <50%. The lymphocyte percentage was negatively associated with the probability of a positive effusion culture (OR 0.97; 95% CI 0.96 to 0.99). The diagnostic yields were 63% for effusion culture, 48% for sputum culture, 79% for the combination of effusion and sputum cultures, and 74% for histological examination of pleural biopsy specimens. CONCLUSION: The degree of lymphocyte predominance in tuberculous pleurisy was lower than was previously thought. The lymphocyte percentage in pleural fluid was negatively associated with the probability of a positive effusion culture. With the implementation of a liquid culture method, the sensitivity of effusion culture was much higher than has been previously reported, and the combination of effusion and sputum cultures provided a good diagnostic yield.

Compliance and barriers to implementing the sepsis resuscitation bundle for patients developing septic shock in the general medical wards.

BACKGROUND/PURPOSE: This two-part study aimed to investigate compliance with the sepsis resuscitation bundle (SRB) and the barriers to its implementation for patients developing septic shock in the general medical wards. METHODS: In the first part, medical records of patients who were admitted to the intensive care unit from the general medical wards due to septic shock were reviewed. Compliance rates with the six SRB components were assessed. In the second part, responsible junior physicians (first-year and second-year residents) in the general wards and senior physicians (third-year residents and fellows) were randomly invited for questionnaire-based interviews. RESULTS: In the first part, during the 6-month study period, 40 patients were included. Overall compliance with the SRB within 6 h was only 2.5%, mainly due to femoral catheterization (42.5%) and the lack of measuring central venous oxygen saturation (ScvO2). Delayed completion of SRB components contributed little to the low compliance rate. In the second part, based on the questionnaire results of 71 junior physicians and 64 senior physicians, the junior physicians were less familiar with the SRB guidelines, particularly regarding the meaning of ScvO2 (p = 0.01) and management of low ScvO2 (p = 0.04). Junior physicians were also more reluctant to measure the central venous pressure (CVP; p = 0.04) and the ScvO2 (p = 0.01), and were also less confident with internal jugular vein or subclavian vein catheterization (p < 0.001). CONCLUSION: Compliance with the SRB for patients developing septic shock in the general medical wards is very low. Besides providing educational programs to improve awareness and acceptance of the SRB, measures to help in central venous catheterization and completion of SRB may be considered.

Evaluating NG-Test CARBA 5 Multiplex Immunochromatographic and Cepheid Xpert CARBA-R Assays among Carbapenem-Resistant Enterobacterales Isolates Associated with Bloodstream Infection.

Decreased susceptibility to carbapenems in Enterobacterales is an emerging concern. Conventional methods with short turnaround times are crucial for therapeutic decisions and infection control. In the current study, we used the Xpert CARBA-R (Cepheid, Sunnyvale, CA, USA) and the NG-Test CARBA 5 (NG Biotech, Guipry, France) assays for carbapenemase detection in 214 carbapenem-resistant Enterobacterales (CRE) blood isolates. We used the modified carbapenem inactivation method, conventional PCR, and sequencing to determine the production of five common carbapenemase families and their subtypes. We performed wzc-genotyping for all CR-Klebsiella pneumoniae (CRKP) and multilocus sequence typing for all carbapenemase-producing CRE isolates to reveal their genetic relatedness. The results showed a sensitivity of 99.8% and a specificity of 100% by the Xpert assay, and a sensitivity of 100% and a specificity of 99% by the NG-Test in detecting carbapenemases of 84 CRKP isolates with only one (VIM-1+IMP-8) failure in both tests. For CR-Escherichia coli, four carbapenemase-producing isolates were detected accurately for their subtypes. The two major clones of carbapenemase-producing CRKP isolates in Taiwan were ST11-K47 producing KPC-2 (n = 47) and ST11-K64 producing OXA-48-like (n = 9). Our results support the use of either test in routine laboratories for the rapid detection of common carbapenemases. Caution should be taken using the Xpert assay in areas with a high prevalence of CRE carrying blaIMP-8. IMPORTANCE Carbapenemase-producing Enterobacterales (CPE) are emerging worldwide, causing nosocomial outbreaks and even community-acquired infections since their appearance 2 decades ago. Our previous national surveillance of CPE isolates in Taiwan identified five carbapenemase families (KPC, OXA, NDM, VIM, and IMP) with the KPC-2 and OXA-48-like types predominant. Timely detection and classification of carbapenemases in CPE may be a useful test to guide optimal therapy and infection control. Genetic detection methods using the Xpert CARBA-R assay and the immunochromatographic assay using the NG-Test CARBA 5 have been validated with the advantage of short turnaround time. Our study demonstrated that the NG and Xpert assays are convenient methods to accurately identify carbapenemases in carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Escherichia coli blood isolates. Detecting IMP variants remains challenging, and the results of Xpert CARBA-R assay should be carefully interpreted.

Acinetobacter baumannii and Acinetobacter genospecies 13TU and 3 bacteraemia: comparison of clinical features, prognostic factors and outcomes.

OBJECTIVES: To investigate the clinical impact of different genospecies of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex (ACB complex; A. baumannii, Acinetobacter gen. sp. 13TU and Acinetobacter gen. sp. 3) on the severity of bacteraemia. METHODS: We retrospectively compared the clinical features and outcomes of patients with bacteraemia caused by A. baumannii, Acinetobacter gen. sp. 13TU or Acinetobacter gen. sp. 3. The genospecies were identified using oligonucleotide array sequence analysis (interspacer sequence), and the clonality of Acinetobacter gen. sp. 13TU and 3 isolates was determined by PFGE analysis. RESULTS: A total of 215 patients with bacteraemia due to ACB complex were evaluated. Among them, 117 (54.4%) had A. baumannii bacteraemia, 77 (35.8%) had Acinetobacter gen. sp. 13TU bacteraemia and 21 (9.8%) had Acinetobacter gen. sp. 3 bacteraemia. A. baumannii bacteraemia was associated with a higher 14 day mortality rate (P < 0.001), a higher 30 day mortality rate (P < 0.001) and a higher in-hospital mortality rate than bacteraemia due to Acinetobacter gen. sp. 13TU or Acinetobacter gen. sp. 3. Independent prognostic factors for the 30 day mortality included the Charlson co-morbidity index (P < 0.001) and Pitt bacteraemia score (P < 0.001). Bloodstream infection caused by a multidrug-resistant A. baumannii isolate appeared to be associated with a poor outcome (P = 0.069). There was no clonal spread of Acinetobacter gen. sp. 13TU or Acinetobacter gen. sp. 3 during the study period. CONCLUSIONS: Bacteraemia due to multidrug-resistant strains but not A. baumannii per se appears to be associated with poor outcome.

Comparison of Etest and broth microdilution for evaluating the susceptibility of Staphylococcus aureus and Streptococcus pneumoniae to ceftaroline and of carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa to ceftazidime/avibactam.

OBJECTIVES: Decreased susceptibility to ceftazidime/avibactam (CZA) and ceftaroline (CPT) has been reported during antimicrobial resistance surveillance and therapy. Conventional laboratories are unable to provide timely susceptibility testing for CZA and CPT because these antimicrobial agents are not incorporated in automated susceptibility testing systems. METHODS: We evaluated Etest and the Sensititre broth microdilution (BMD) method for testing CZA against carbapenem-resistant Gram-negative bacilli and CPT against important Gram-positive cocci bloodstream isolates. Genotypes of carbapenemases in Enterobacterales were also determined using the Xpert® Carba-R assay. RESULTS: Etest showed ≥90% agreement with Sensititre BMD for carbapenem-resistant Klebsiella pneumoniae (CRKP) (n = 187), carbapenem-resistant Escherichia coli (CREC) (n = 28) and Streptococcus pneumoniae (n = 35); however, the very major error rate exceeded 3%. Agreement between Etest and Sensititre BMD was <90% for carbapenem-resistant Pseudomonas aeruginosa (CRPA) (n = 81), methicillin-susceptible Staphylococcus aureus (MSSA) (n = 92) and methicillin-resistant S. aureus (MRSA) (n = 170). Both agents remained potent with a high susceptibility rate by Sensititre BMD as follows: CZA against CRKP (95.0%), CREC (89.3%) and CRPA (84.5%); and CPT against MSSA (100.0%), MRSA (95.3%) and S. pneumoniae (94.3%). CZA was active against blaKPC-carrying CRKP (98.5% susceptible), and resistance in the majority of CZA-resistant Enterobacterales isolates (6 of 10 CRKP and 2 of 3 CREC) was due to the presence of a metallo-ß-lactamase gene. CONCLUSION: Our results suggest that interpretation of susceptibility results obtained by Etest for both agents should be undertaken cautiously and remains challenging.

Clinical and molecular epidemiology of human listeriosis in Taiwan.

OBJECTIVE: To determine serogroups, multilocus sequence typing (MLST) of Listeria monocytogenes isolates and analyze clinical characteristics of these clones focusing on non-perinatal cases. METHODS: From 2000 to 2015, we analyzed 123 human listeriosis cases at a medical center in northern Taiwan using PCR serogrouping, MLST, and clinical presentations. RESULTS: The annual incidence of listeriosis increased since 2005 with a peak in 2008 (0.2 per 1000 admission) and decreased thereafter. Of the 115 non-perinatal listeriosis cases, we found a male predominance (60%) with an average age of 63.9 years old (standard deviation: 15.3 years), and almost all patients had underlying conditions including malignancies (61.7%), steroid usage (39.1%), diabetes mellitus (31.3%), renal insufficiency (27.8%), and liver cirrhosis (17.4%). Clinical presentations included bacteremia (74.8%), neurolisteriosis (20.0%), and spontaneous bacterial peritonitis (5.2%). The most frequently identified serogroup-sequence types (ST) were IIB-ST87 (30.9%), followed by IIA-ST378 (16.3%) and IIA-ST155 (14.6%). The 30-day all-cause mortality of non-perinatal listeriosis was 25.2% and was associated with age (Hazard ratio: 1.04, 95% C.I. = 1.01-1.07, p = 0.021), steroid usage (Hazard ratio: 2.54, 95% C.I. = 1.06-6.11, p = 0.038) and respiratory distress at presentation (Hazard ratio: 2.59, 95% C.I. = 1.05-6.39, p = 0.038); while no association was found with serogroups (IIA, IIB, and IVB) or three major ST types by multivariable analysis. All 8 mothers of perinatal listeriosis patients survived and three neonates died (mortality, 37.5%), and IIB-ST87 was the major type (62.5%). CONCLUSION: Predominant strains in Taiwan could cause significant morbidity and mortality. Further disease monitoring and source surveillance are warranted despite a declining trend of human listeriosis in Taiwan.

Association of weaning preparedness with extubation outcome of mechanically ventilated patients in medical intensive care units: a retrospective analysis.

BACKGROUND: Assessment of preparedness of weaning has been recommended before extubation for mechanically ventilated patients. We aimed to understand the association of a structured assessment of weaning preparedness with successful liberation. METHODS: We retrospectively investigated patients with acute respiratory failure who experienced an extubation trial at the medical intensive care units of a medical center and compared the demographic and clinical characteristics between those patients with successful and failed extubation. A composite score to assess the preparedness of weaning, the WEANSNOW score, was generated consisting of eight components, including Weaning parameters, Endotracheal tube, Arterial blood gas analysis, Nutrition, Secretions, Neuromuscular-affecting agents, Obstructive airway problems and Wakefulness. The prognostic ability of the WEANSNOW score for extubation was then analyzed. RESULTS: Of the 205 patients included, 138 (67.3%) patients had successful extubation. Compared with the failure group, the success group had a significantly shorter duration of MV before the weaning attempt (11.2 ± 11.6 vs. 31.7 ± 26.2 days, p < 0.001), more with congestive heart failure (42.0% vs. 25.4%, p = 0.020), and had different distribution of the types of acute respiratory failure (p = 0.037). The failure group also had a higher WEANSNOW score (1.22 ± 0.85 vs. 0.51 ± 0.71, p < 0.001) and worse Rapid Shallow Breathing Index (93.9 ± 63.8 vs. 56.3 ± 35.1, p < 0.001). Multivariate logistic regression analysis showed that a WEANSNOW Score = 1 or higher (OR = 2.880 (95% CI [1.291-6.426]), p = 0.010) and intubation duration >21 days (OR = 7.752 (95% CI [3.560-16.879]), p < 0.001) were independently associated with an increased probability of extubation failure. CONCLUSION: Assessing the pre-extubation status of intubated patients in a checklist-based approach using the WEANSNOW score might provide valuable insights into extubation failure in patients in a medical ICU for acute respiratory failure. Further prospective studies are warranted to elucidate the practice of assessing weaning preparedness.