Jung-Yien Chien

Invasive Trichosporonosis Caused by Trichosporon asahii and Other Unusual Trichosporon Species at a Medical Center in Taiwan

BACKGROUND During the past 2 decades, invasive trichosporonosis has emerged as an opportunistic infectious disease in immunocompromised patients. However, no case series have been reported recently. METHODS All patients with a culture that was positive for Trichosporon species from May 2000 through May 2008 at a medical center were evaluated. The identity of all Trichosporon species was confirmed by analysis of the intergenic spacer 1 region of the fungal ribosomal RNA gene. In vitro susceptibility testing was performed using the reference broth microdilution method. RESULTS Forty-three patients were found to have a culture that was positive for Trichosporon species. T. asahii was the most frequently isolated species (32 isolates; 74%), followed by T. dermatis (5; 12%), T. montevideense (2; 5%), and T. asteroides (1; 2%), T. cutaneum (1; 2%), T. faecale (1; 2%), and T. ovoides (1; 2%). Nineteen patients had invasive infections; 16 (84%) were caused by T. asahii, and 1 (5%) each was caused by T. dermatis, T. montevideense, and T. asteroides. Of the 19 episodes of invasive trichosporonosis, 14 (74%) were fungemia, 3 (16%) were pulmonary infection, and 1 (5%) each was soft-tissue infection and meningitis. Most invasive infections were associated with prior antibiotic therapy (95%), use of a central catheter (90%), malignancy (58%), and intensive care unit admission (47%). Azoles had good in vitro activity, whereas amphotericin B and echinocandins were not active against Trichosporon isolates. The 30-day all-cause mortality rate was 42% and was higher among patients with a malignancy (55%) than among those without an underlying malignancy (25%). CONCLUSIONS Invasive trichosporonosis tended to develop in patients with an underlying malignancy and to be associated with higher mortality. T. asahii and other unusual Trichosporon species may cause invasive trichosporonosis.

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.

Changes in B-type natriuretic peptide improve weaning outcome predicted by spontaneous breathing trial

LEARNING OBJECTIVESOn completion of this article, the reader should be able to:Explain the significance of B-type natriuretic peptide (BNP) elevation in critically ill patients.Describe the predictive value of BNP in decisions to remove ventilator support.Use this information in a clinical setting.The authors have disclosed that they have no financial relationships with or interests in any commercial companies pertaining to this educational activity.All faculty and staff in a position to control the content of this CME activity have disclosed that they have no financial relationship with, or financial interests in, any commercial companies pertaining to this educational activity.Lippincott CME Institute, Inc., has identified and resolved all faculty conflicts of interest regarding this educational activity.Vist the Critical Care Medicine Web Site (www.ccmjournal.org) for information on obtaining continuing medical education credit. Objective:Despite the use of spontaneous breathing trial (SBT), predicting weaning success remains a major clinical challenge. Because cardiovascular dysfunction could be a major underlying mechanism of weaning failure, we evaluated the role of the levels of B-type natriuretic peptide (BNP), a marker for cardiovascular function, in patients who passed a 2-hr SBT. Design, Setting, and Patients:Fifty-two patients recovering from acute respiratory failure were enrolled as the testing group to determine the predictive value of BNP. The predictive value of BNP was validated in a second independent cohort of 49 patients. Then, we combined both groups of patients to conduct the final analysis. Measurements and Results:In the testing group of 52 patients, 41 passed SBT and were extubated. Of these patients, 33 patients (80%) were extubated successfully (extubation success) while eight patients (20%) were reintubated within 48 hrs (extubation failure). There were no differences in the baseline BNP levels, but the extubation failure group had significantly greater increases in BNP at the end of SBT than the extubation success groups (32.7%, 25th–75th percentile = 25.7%−50.8% vs. 0.69%, −8.8%−10.72%, p < .001). The area under the receiver operating characteristic curves for the BNP change was 0.93 and an increase of BNP <20% during SBT had the best combination of sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for predicting extubation success (91%, 88%, 97%, 70%, and 91%). This threshold value of BNP change was then validated in an independent cohort. Combining BNP with SBT as extubation criteria increased the extubation success rate to 95% from 78% using SBT alone (p = .035). Conclusion:Measuring the percentage change in the BNP level during a SBT may help improve the predictive value of SBT on weaning outcome.

Pulmonary infection and colonization with nontuberculous mycobacteria, Taiwan, 2000-2012.

We analyzed samples from 13,652 patients who had respiratory cultures positive for mycobacteria in Taiwan during 2000–2012 and found that 56.9% were positive for nontuberculous mycobacteria (NTM). Whereas annual prevalence of tuberculosis decreased during the study period, prevalence of NTM disease and colonization increased, particularly among older patients and male patients.

Temporal changes in cytokine/chemokine profiles and pulmonary involvement in severe acute respiratory syndrome

Objective and background:  Pathological changes in severe acute respiratory syndrome (SARS) suggest that SARS sequelae are associated with dysregulation of cytokine and chemokine production. To improve understanding of the immuno‐pathological processes involved in lung injury associated with SARS, the temporal changes in cytokine/chemokine profiles in the sera of SARS patients were compared with those of patients with community‐acquired pneumonia (CAP), according to the degree of lung involvement.

Decline in rates of acquired multidrug-resistant tuberculosis after implementation of the directly observed therapy, short course (DOTS) and DOTS-Plus programmes in Taiwan

OBJECTIVES To investigate the impact of the directly observed therapy, short course (DOTS) and DOTS-Plus strategies on changes in resistance profiles among Mycobacterium tuberculosis (MTB). METHODS We performed a retrospective analysis of resistance profiles among isolates of MTB obtained from 2160 consecutive patients with culture-confirmed pulmonary tuberculosis (TB) between 2005 and 2011 at a referral centre in southern Taiwan. RESULTS Of the 2160 patients, 70 (3.2%) had primary multidrug-resistant (MDR)-TB, 178 (8.2%) had acquired MDR-TB, 10 (0.5%) had primary extensively drug-resistant (XDR)-TB, 23 (1.1%) had acquired XDR-TB and 5 (0.2%) had totally drug-resistant (TDR)-TB. Trend analysis revealed that the rates of acquired MDR-TB were significantly lower after implementation of the DOTS and DOTS-Plus programmes (P < 0.01). There was a significant negative correlation between the coverage rates of the DOTS and DOTS-Plus programmes and the rates of acquired MDR-TB (r = -0.84, P = 0.02 and r = -0.92, P = 0.03, respectively). The rates of resistance to rifampicin, isoniazid, ofloxacin, moxifloxacin, levofloxacin and para-aminosalicylic acid also decreased significantly during the study period. However, the rates of primary MDR-TB remained stable (P = 0.11). Multivariate logistic regression analysis showed that age ranging from 45 to 64 years, positive acid-fast stain results at the initiation of treatment and treatment without DOTS were independent risk factors associated with acquired MDR-TB. In addition, previous treatment for TB (100% versus 19% for TDR-TB and non-TDR-TB, P < 0.01) and treatment without DOTS (80% versus 44% for TDR-TB and non-TDR-TB, P = 0.18) were risk factors for TDR-TB. CONCLUSIONS DOTS and DOTS-Plus are both effective at preventing the acquisition of MDR-TB in Taiwan.

Treatment outcome of patients with isoniazid mono-resistant tuberculosis

Isoniazid mono-resistance is the most common first-line drug resistance in tuberculosis (TB), but its treatment outcome remains unclear. From January 2004 to October 2011, 425 (5.1%) of 8414 patients with culture-confirmed pulmonary TB from four hospitals in Taiwan were identified as having isoniazid mono-resistant TB. Among them, 395 (92.9%) were included and followed up for 2 years after complete treatment. Although 328 (83.0%) patients were successfully treated, 67 (17.0%) had unfavourable outcomes, including death in 56 (14.2%) and treatment failure in 11 (2.8%). The treatment success rate was similar in patients with high-level and low-level isoniazid-resistant TB (82.2% versus 83.4%, p 0.785) and among those taking anti-TB treatment with and without isoniazid (83.1% versus 83.0%, p 1.000). Patients without rifampicin interruption had lower risk of unfavourable outcome (14.3% versus 37.0%, p <0.001), especially those with low-level isoniazid resistance (11.5% versus 56.5%, p <0.001). Supplementation with a new-generation fluoroquinolone improved treatment success (60.0% versus 12.5%, p 0.003). The presence of cavitary lesions was significantly associated with a higher relapse rate (4.1% versus 0.0%, p 0.006) and extended treatment of 7-9, 10-12 and >12 months had less relapse than 6-month treatment (3.2%, 0%, 3.7% and 25.0%, respectively, p 0.037). Multivariate Cox proportional hazards analysis revealed that co-morbidity with cancer (hazard ratio, 2.43) and rifampicin interruption (hazard ratio 1.91) were independent factors associated with unfavourable outcomes. Treatment throughout with rifampicin and extended treatment for cavitary disease are crucial for improving outcomes in patients with isoniazid mono-resistant TB.

Mutations in gyrA and gyrB among Fluoroquinolone- and Multidrug-Resistant Mycobacterium tuberculosis Isolates

ABSTRACT In order to correlate the mutations inside the entire gyrA and gyrB genes with the level of resistance to ofloxacin (OFX) and moxifloxacin (MFX) in isolates of multidrug-resistant Mycobacterium tuberculosis (MDR-TB), a total of 111 isolates were categorized into OFX-susceptible (MIC, ≤2 μg/ml) and low-level (MIC, 4 to 8 μg/ml) and high-level (MIC, ≥16 μg/ml) OFX-resistant isolates and MFX-susceptible (MIC, ≤0.5 μg/ml) and low-level (MIC, 1 to 2 μg/ml) and high-level (MIC, ≥4 μg/ml) MFX-resistant isolates. Resistance-associated mutations inside the gyrA gene were found in 30.2% of OFX-susceptible and 72.5% and 72.2% of low-level and high-level OFX-resistant isolates and in 28.6% of MFX-susceptible and 58.1% and 83.9% of low-level and high-level MFX-resistant isolates. Compared with OFX-susceptible isolates, low-level and high-level OFX-resistant isolates had a significantly higher prevalence of mutations at gyrA codons 88 to 94 (17.0%, 65.0%, and 72.2%, respectively; P < 0.001) and a higher prevalence of the gyrB G512R mutation (0.0%, 2.5%, and 16.7%, respectively; P = 0.006). Similarly, compared with MFX-susceptible isolates, low-level and high-level MFX-resistant isolates had a significantly higher prevalence of mutations at gyrA codons 88 to 94 (14.3%, 51.6%, and 80.6%, respectively; P < 0.001) as well as a higher prevalence of the gyrB G512R mutation (0.0%, 0.0%, and 12.9%, respectively; P = 0.011). D94G and D94N mutations in gyrA and the G512R mutation in gyrB were correlated with high-level MFX resistance, while the D94A mutation was associated with low-level MFX resistance. The prevalence of mutations at gyrA codons 88 to 94 and the gyrB G512R mutation were higher among fluoroquinolone (FQ)-susceptible East Asian (Beijing) and Indo-Oceanic strains than they were among Euro-American strains, implying that molecular techniques to detect FQ resistance may be less specific in areas with a high prevalence of East Asian (Beijing) and Indo-Oceanic strains.

The evolution of drug-resistant microorganisms in patients with prolonged mechanical ventilation.

BACKGROUND Patients requiring prolonged mechanical ventilation (PMV) tend to become reservoirs of antimicrobial resistance. We assessed antimicrobial-resistant microorganisms in the respiratory tracts of patients receiving PMV. METHODS Over a 6-month period, the microorganisms from tracheal aspirates of PMV patients with lower airway infection were analyzed. RESULTS Antimicrobial use was greatest during the acute critical stage of respiratory failure. Antimicrobial resistance in Pseudomonas aeruginosa and Klebsiella pneumoniae peaked during the fourth to 15th weeks of PMV. Methicillin-resistant Staphylococcus aureus (MRSA) developed rapidly during the first 3 weeks of PMV. The acquisition of multidrug-resistant P aeruginosa and MRSA were significantly correlated with previous exposure to ceftazidime (odds ratio [OR] = 121.3 and 72.5; P = .01 and .01, respectively). The rise of multidrug-resistant Acinetobacter baumannii was significantly correlated with previous exposure to piperacillin/tazobactam (OR = 26.81; P = .02) and imipenem (OR = 16.91; P = .03). Using univariate and multivariate logistic regression models, the lower respiratory tract infections with multidrug-resistant microorganisms were independently associated with increased 6-month mortality (OR = 3.41; P < .01). CONCLUSION In patients receiving PMV, lower respiratory tract infection with multidrug-resistant microorganisms is common and is associated with higher mortality.

Safety of rifabutin replacing rifampicin in the treatment of tuberculosis: a single-centre retrospective cohort study

OBJECTIVES The safety of rifabutin replacing rifampicin among adults having rifampicin-related adverse reactions (ARs) during the treatment of tuberculosis remains unknown. METHODS From June 2006 to June 2010, a total of 2868 newly treated tuberculosis patients without HIV infection in a referral hospital were screened in this retrospective cohort study. RESULTS Among the screened patients, a total of 221 (8%) patients who received rifabutin replacing rifampicin were included. Of these patients, 158 (72%) tolerated rifabutin during treatment, but 47 (21%) and 16 (7%) experienced mild and severe rifabutin-related ARs (including neutropenia, severe hepatitis and uveitis), respectively, and needed to discontinue rifabutin. Those having previous rifampicin-related arthralgia, dermatological events and cholestasis had a higher AR recurrence rate (60%, 23% and 9%, respectively) than others (5% for hepatitis and gastrointestinal intolerance and 0% for flu-like syndrome, neutropenia and others; P < 0.01). Multivariate logistic regression analysis showed that females (OR 3.35; 95% CI 1.06-10.56; P = 0.04) and patients with hepatitis virus B (HBV) or hepatitis C virus (HCV) coinfection (OR 3.72; 95% CI 1.19-11.67; P = 0.02) were at a higher risk of rifabutin-related severe ARs. No development of new drug resistance and no relapse of tuberculosis were found during 2 years of follow-up. CONCLUSIONS Rifabutin replacing rifampicin was well tolerated in most adults who had rifampicin-related ARs. Females and those with HCV or HBV coinfection were more prone to rifabutin-related severe ARs and required more cautious monitoring.