Clinical manifestations and risk factors for COVID-19 and its severity in patients with hematological malignancies.

BACKGROUND: Patients with hematological malignancies (HM) were at a high risk of developing severe disease from coronavirus disease 2019 (COVID-19). We aimed to assess the clinical outcome of COVID-19 in hospitalized patients with HM. METHODS: Adult patients with HM who were hospitalized with a laboratory-confirmed COVID-19 between May, 2021 and November, 2022 were retrospectively identified. Primary outcome was respiratory failure requiring mechanical ventilation or mortality within 60 days after hospitalization. We also analyzed associated factors for de-isolation (defined as defervescence with a consecutive serial cycle threshold value > 30) within 28 days. RESULTS: Of 152 eligible patients, 22 (14.5%) developed respiratory failure or mortality in 60 days. Factors associated with developing respiratory failure that required mechanical ventilation or mortality included receipt of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) (adjusted hazards ratio [aHR], 5.10; 95% confidence interval [CI], 1.64-15.85), type 2 diabetes mellitus (aHR, 2.47; 95% CI, 1.04-5.90), lymphopenia at admission (aHR, 6.85; 95% CI, 2.45-19.15), and receiving <2 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines (aHR, 3.00; 95% CI, 1.19-7.60). Ninety-nine (65.1%) patients were de-isolated in 28 days, against which two hazardous factors were identified: receipt of B-cell depletion therapies within one year prior to COVID-19 (aHR, 0.55, 95% CI, 0.35-0.87) and lymphopenia upon admission (aHR, 0.65; 95% CI, 0.43-1.00). CONCLUSION: We found a high rate of respiratory failure and mortality among patients with HM who contracted the SARS-CoV-2. Factors associated with developing respiratory failure or mortality in 60 days included receipt of allo-HSCT, type 2 diabetes mellitus and lymphopenia upon admission. Having received ≥2 doses of vaccination conferred protection against clinical progression.

Case Report: Pericardial Actinomycosis in a 79-Year-Old Man with Poor Dental Hygiene.

Actinomycosis is an uncommon infection caused by Actinomyces species, and the diagnosis is often challenging owing to low prevalence and diverse clinical manifestations. Pericardial involvement of actinomycosis is particularly rare. Here, we present a case of a 79-year-old man who initially complained of exertional dyspnea, orthopnea, and decreased urine amount. There was no fever, chest pain, or productive cough. Physical examination was remarkable for decreased breath sounds at the left lower lung field. Poor dental hygiene and a firm, well-defined mass without discharge over the hard palate were noted. Echocardiography revealed reduced ejection fraction of the left ventricle, global hypokinesia, and thickened pericardium (> 5 mm) with a small amount of pericardial effusion. On admission, the patient underwent diagnostic thoracentesis, and the results suggested an exudate. However, bacterial and fungal cultures were all negative. There was no malignant cell by cytology. Computed tomography revealed contrast-enhanced pericardial nodular masses. Video-assisted thoracoscopic pericardial biopsy was performed. Histopathology confirmed actinomycosis with chronic abscess formation, and a tissue culture yielded Aggregatibacter actinomycetemcomitans. The symptoms resolved with administration of clindamycin for 6 months. This case highlights the challenge in the diagnosis of cardiac actinomycosis, the potential role of concomitant microorganisms as diagnostic clues, and the favorable clinical response achieved with appropriate antibiotic treatment.

CXCL9 as a Reliable Biomarker for Discriminating Anti-IFN-γ-Autoantibody-Associated Lymphadenopathy that Mimics Lymphoma.

The diagnosis of adult-onset immunodeficiency syndrome associated with neutralizing anti-interferon γ autoantibodies (AIGA) presents substantial challenges to clinicians and pathologists due to its nonspecific clinical presentation, absence of routine laboratory tests, and resemblance to certain lymphoma types, notably nodal T follicular helper cell lymphoma, angioimmunoblastic type (nTFHL-AI). Some patients undergo lymphadenectomy for histopathological examination to rule out lymphoma, even in the absence of a preceding clinical suspicion of AIGA. This study aimed to identify reliable methods to prevent misdiagnosis of AIGA in this scenario through a retrospective case-control analysis of clinical and pathological data, along with immune gene transcriptomes using the NanoString nCounter platform, to compare AIGA and nTFHL-AI. The investigation revealed a downregulation of the C-X-C motif chemokine ligand 9 (CXCL9) gene in AIGA, prompting an exploration of its diagnostic utility. Immunohistochemistry (IHC) targeting CXCL9 was performed on lymph node specimens to assess its potential as a diagnostic biomarker. The findings exhibited a significantly lower density of CXCL9-positive cells in AIGA compared to nTFHL-AI, displaying a high diagnostic accuracy of 92.3% sensitivity and 100% specificity. Furthermore, CXCL9 IHC demonstrated its ability to differentiate AIGA from various lymphomas sharing similar characteristics. In conclusion, CXCL9 IHC emerges as a robust biomarker for differentiating AIGA from nTFHL-AI and other similar conditions. This reliable diagnostic approach holds the potential to avert misdiagnosis of AIGA as lymphoma, providing timely and accurate diagnosis.

Comparison of post-COVID-19 vaccination hypermetabolic lymphadenopathy on 18F-fluorodeoxyglucose PET/CT between virus-vector vaccine and mRNA vaccine.

PURPOSE: We compared hypermetabolic lymphadenopathy (HLN) on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) after virus-vector and mRNA vaccines for coronavirus disease 2019 (COVID-19). METHODS: This retrospective study included 573 participants who underwent FDG PET/CT after receiving a virus-vector vaccine (ChAdOx1, AstraZeneca [AZ] group) or an mRNA vaccine (mRNA-1273, Moderna [M] group) from July 2021 to October 2021. The incidence and avidity of HLN were evaluated and correlated with clinical features and vaccine type. The final analysis was conducted with 263 participants in the AZ group and 310 participants in the M group. RESULTS: The HLN incidence was significantly lower in the AZ group than in the M group (38/263 [14%] vs. 74/310 [24%], p = 0.006). The FDG avidity of HLN was comparable between the two groups. The HLN incidence in both groups was significantly higher within 4 weeks after the vaccination compared with more than 4 weeks. The HLN incidence within 4 weeks of the vaccination was significantly higher in the M group than in the AZ group (p = 0.008), whereas a difference in HLN incidence between the two groups was not observed after the same duration (p = 0.11). CONCLUSIONS: The mRNA mRNA-1273 COVID-19 vaccine was found to be associated with higher glucose hypermetabolism in regional lymph nodes within the first 4 weeks compared with the virus-vector vaccine, as indicated by the presence of HLN on FDG PET/CT. The degree of glucose hypermetabolism was comparable between the two vaccines.

Pyrazinamide related prolonged drug-induced liver injury: A case report.

RATIONALE: Drug induced liver injury (DILI) is a common side effect causing treatment discontinuation during tuberculosis (TB) treatment, and pyrazinamide (PZA) usually leads to a delayed and prolonged abnormal liver function of the 4 standard anti-tuberculosis regimens. However, a prolonged hepatitis lasting more than 4 months is rarely reported. PATIENT CONCERNS: A 78-year-old man presented with general weakness and poor appetite on his seventh week of anti-TB treatment for tuberculosis lymphadenitis. DIAGNOSIS: Drug induced liver injury, PZA-related. NAT2 slow acetylator phenotype was accidentally found during workup of DILI. INTERVENTION: A liver biopsy was performed and PZA-related DILI was suspected. All anti-TB medications were therefore discontinued. OUTCOME: After withholding all anti-TB medications for 4 months, the elevations of aminotransferases and hyperbilirubinemia completely resolved. Anti-TB therapy was switched to ethambutol and levofloxacin for 15 months without adverse events. Long-term ultrasound follow-up was performed and cervical lymphadenopathy completely resolved. CONCLUSION: Our patient presents with PZA related prolonged DILI resolved after drug discontinuation for 4 months. NAT2 slow acetylator phenotype may be related to this condition through unknown mechanisms.

Discovery and characterization of a monoclonal antibody targeting a conformational epitope of IL-6/IL-6Rα to inhibit IL-6/ IL-6Rα/gp130 hexameric signaling complex formation.

The functional interleukin 6 (IL-6) signaling complex is a hexameric structure composed of IL-6, IL-6Rα, and the signaling receptor gp130. There are three different modes of IL-6 signaling, classic signaling, trans-signaling, and trans-presentation, which are not functionally redundant and mediate pleiotropic effects on both physiological and pathophysiological states. Monoclonal antibodies against IL-6 or IL-6Rα have been successfully developed for clinical application. However, designing therapeutic interventions that block specific modes of IL-6 signaling in a pathologically relevant manner remains a great challenge. Here, we constructed a fusion protein Hyper-IL-6 (HyIL-6) composed of human IL-6 and IL-6Rα to develop specific blocking antibodies against the IL-6/IL-6Rα complex. We successfully screened the monoclonal antibody C14mab, which can bind to HyIL-6 with the binding constant 2.86 × 10-10 and significantly inhibit IL-6/IL-6Rα/gp130 complex formation. In vitro, C14mab effectively inhibited HyIL-6-stimulated signal transducer and activator of transcription 3 (STAT3) activation and related vascular endothelial growth factor (VEGF) induction. Moreover, C14mab efficaciously suppressed HyIL-6-induced acute phase response in vivo. Our data from hydrogen-deuterium exchange mass spectrometry demonstrate that C14mab mainly binds to site IIIa of IL-6 and blocks the final step in the interaction between gp130 and IL-6/IL-6Rα complex. Additionally, data from enzyme-linked immunosorbent assays and kinetics assays indicate that C14mab interacts simultaneously with IL-6 and IL-6Rα, while it does not interact with IL-6Rα alone. The unique features of C14mab may offer a novel alternative for IL-6 blockade and illuminate a better therapeutic intervention targeting IL-6.

Neutralizing Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in Patients With Central Nervous System and Localized Cryptococcosis: Longitudinal Follow-up and Literature Review.

BACKGROUND: Neutralizing anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (AAbs) have been increasingly recognized to predispose healthy individuals to disseminated cryptococcosis. However, studies have only considered patients with central nervous system (CNS) infection. No longitudinal study has captured the disease spectrum and clinical course. METHODS: We prospectively enrolled adults without human immunodeficiency virus infection who had disseminated or unusual cryptococcosis. We compared the demographics, clinical features, kinetics of serum cryptococcal antigen (CrAg) titers, anti-GM-CSF AAb concentrations, and treatment outcomes between patients with (case patients) and without (control patients) anti-GM-CSF AAbs. Additional reports from the literature were also reviewed. RESULTS: Twenty-three patients were enrolled, of whom 6 tested positive for anti-GM-CSF AAbs. All case patients with positive fungal cultures (5/5 [100%]) were infected with Cryptococcus gattii VGII. Among them, 3 had exclusively pulmonary involvement, and 1 had only musculoskeletal lesions. Patients with CNS cryptococcosis exhibited a higher serum concentration of anti-GM-CSF AAbs than those with extraneural cryptococcosis. Case patients had higher initial and peak levels of serum CrAg and longer duration of antigenemia compared with the control patients. All case patients who had completed antifungal therapy had favorable outcomes without recurrence. CONCLUSIONS: Testing for anti-GM-CSF AAbs should be considered for not only previously healthy patients with disseminated cryptococcosis but also those with unexplained, localized cryptococcosis. Recurrence after completion of antifungal therapy was rare despite the persistence of anti-GM-CSF AAbs.

Clinical characteristics and outcomes of non-cystic fibrosis patients with Burkholderia cepacia complex bacteremia at a medical center in Taiwan.

BACKGROUND: Burkholderia cepacia complex (BCC) represents a group of multidrug-resistant gram-negative bacteria that cause infections among immunocompromised hosts. Bacteremia occurs in patients who are chronically ill and is associated with substantial morbidity and mortality. The aim of this study was to investigate the clinical characteristics and outcomes of BCC bacteremic patients without cystic fibrosis. METHODS: We conducted a retrospective study at the National Taiwan University Hospital. Adults with BCC bacteremia from January 2015 to May 2019 were enrolled. The primary outcome was 14-day mortality. Multivariable logistic regression was performed for outcome analysis. RESULTS: One-hundred and ninety-five patients were analyzed and their mean age was 67 years. Over 95% of the BCC isolates were susceptible to trimethoprim/sulfomethoxazole (TMP/SXT). Levofloxacin resistance rates were high, with only 25.1% of isolates being susceptible. Pairwise comparisons were made between different definitive regimens including meropenem-monotherapy, ceftazidime-monotherapy, levofloxacin-monotherapy, TMP/SXT-monotherapy, tigecycline-monotherapy as well as combination versus monotherapy. No regimen was significantly associated with survival in our study. Multivariable logistic regression showed that the Pitt bacteremia score (adjust odds ratio [aOR],1.46; 95% confidence interval [CI],1.19-1.79; p < 0.001), underlying metastatic cancer (aOR, 2.73; 95% CI, 1.01-7.39; p = 0.047), inappropriate definitive treatment independently predicted greater 14-day mortality (aOR, 8.21; 95% CI, 2.49-27.08; p < 0.001). CONCLUSIONS: No single regimen is associated with improved mortality. After adjusting for other potential confounders, our data suggest selection of an appropriate antibiotic provide better clinical outcomes among patients with BCC bacteremia.

NK cell receptor and ligand composition influences the clearance of SARS-CoV-2.

To explore how the immune system controls clearance of SARS-CoV-2, we used a single-cell, mass cytometry-based proteomics platform to profile the immune systems of 21 patients who had recovered from SARS-CoV-2 infection without need for admission to an intensive care unit or for mechanical ventilation. We focused on receptors involved in interactions between immune cells and virus-infected cells. We found that the diversity of receptor repertoires on natural killer (NK) cells was negatively correlated with the viral clearance rate. In addition, NK subsets expressing the receptor DNAM1 were increased in patients who more rapidly recovered from infection. Ex vivo functional studies revealed that NK subpopulations with high DNAM1 expression had cytolytic activities in response to target cell stimulation. We also found that SARS-CoV-2 infection induced the expression of CD155 and nectin-4, ligands of DNAM1 and its paired coinhibitory receptor TIGIT, which counterbalanced the cytolytic activities of NK cells. Collectively, our results link the cytolytic immune responses of NK cells to the clearance of SARS-CoV-2 and show that the DNAM1 pathway modulates host-pathogen interactions during SARS-CoV-2 infection.

Lymphadenopathy Associated With Neutralizing Anti-interferon-gamma Autoantibodies Could Have Monoclonal T-cell Proliferation Indistinguishable From Malignant Lymphoma and Treatable by Antibiotics: A Clinicopathologic Study.

Early recognition of adult-onset immunodeficiency associated with neutralizing anti-interferon gamma autoantibodies (anti-IFNγ Abs) remains difficult, and misdiagnoses have been reported. Although febrile lymphadenopathy is among the most common initial manifestations of this disorder, no comprehensive clinicopathologic analysis of lymphadenopathy in patients with anti-IFNγ Abs has been reported. Here, we describe 26 lymph node biopsy specimens from 16 patients. All patients exhibited concurrent disseminated nontuberculous mycobacterial infections, and 31% received a tentative diagnosis of lymphoma at initial presentation. We found 3 distinct histomorphologic patterns: well-formed granuloma (46%), suppurative inflammation or loose histiocytic aggregates (31%), and lymphoproliferative disorder (LPD, 23%). The latter shared some of the features of malignant T-cell lymphoma, IgG4-related disease, and multicentric Castleman disease. Half of the specimens with LPD had monoclonal T cells, and 33.3% were indistinguishable from angioimmunoblastic T-cell lymphoma as per current diagnostic criteria. All lymphadenopathy with LPD features regressed with antibiotics without administration of cytotoxic chemotherapy or immunotherapy. The median follow-up time was 4.3 years. Our study highlights the substantial challenge of distinguishing between lymphoma and other benign lymphadenopathy in the setting of neutralizing anti-IFNγ Abs. Increased vigilance and multidisciplinary discussion among clinicians and pathologists are required to achieve the most appropriate diagnosis and management.

Salivary dysbiosis in Sjögren's syndrome and a commensal-mediated immunomodulatory effect of salivary gland epithelial cells.

Salivary gland epithelial cells (SGECs) have been implicated in the pathogenesis of Sjögren's syndrome due to aberrant antigen-presentation function. This study examined the hypothesis that oral dysbiosis modulates the antigen-presentation function of SGECs, which regulates CD4 T cell proliferation in primary Sjögren's syndrome (pSS). Saliva samples from 8 pSS patients and 16 healthy subjects were analyzed for bacterial 16S ribosomal DNA. As a result, 39 differentially abundant taxa were identified. Among them, the phylum Proteobacteria comprised 21 taxa, and this phylum was mostly enriched in the healthy controls. The proteobacterium Haemophilus parainfluenzae was enriched in the healthy controls, with the greatest effect size at the species level. Treatment of A253 cells in vitro with H. parainfluenzae upregulated PD-L1 expression, and H. parainfluenzae-pretreated A253 cells suppressed CD4 T cell proliferation. The suppression was partially reversed by PD-L1 blockade. Among low-grade xerostomia patients, salivary abundance of H. parainfluenzae decreased in pSS patients compared to that in non-pSS sicca patients. Our findings suggest that H. parainfluenzae may be an immunomodulatory commensal bacterium in pSS.

Factors associated with treatment duration and recurrence rate of complicated mastitis.

BACKGROUND: The incidence of mastitis has increased, and this disease can lead to long antibiotic courses and complications. Here, we aimed to identify the factors associated with antibiotic duration and recurrence of complicated mastitis. MATERIALS AND METHODS: This retrospective cohort study was conducted in a tertiary hospital in Taiwan. All hospitalized patients diagnosed with mastitis (ICD-9 code 611.0) from Jan. 1, 2012, to Dec. 31, 2016, were enrolled. Patient characteristics and clinical data were obtained from the medical charts. Recurrence was defined as mastitis within the first year after the discontinuation of antibiotics for at least 7 days. RESULTS: In total, 214 females with a median age of 37 years old (IQR 33-45) were enrolled. A total of 148 patients (69.2%) underwent debridement, and 122 (57.0%) underwent biopsy. Histopathological examinations revealed granulation tissue in 44.6% (62/139) of the patients. Positive cultures were obtained in 65.9% (141/214) of the patients. Coagulase-negative staphylococci (64/141, 45.4%) was the most common pathogen, followed by Corynebacterium species (42/141, 29.8%). The median hospitalization length and antibiotic course were 7 (IQR 4-13) and 37 days (IQR 22-77), respectively. Three patients died of breast cancer during treatment. The recurrence rate was 18.5% (39/211). Younger age, corynebacterial infection, and pregnancy were associated with longer treatment durations (P < 0.001, 0.003, <0.001). Corynebacterial infection was associated with a 2.16-fold (95% CI: 1.11-4.20) increase in recurrence after adjusting for age. CONCLUSION: Corynebacterial infection is associated with longer treatment courses and an increased recurrence rate of complicated mastitis. Therefore, specific treatments should be considered.

Implementation of human factors engineering approach to improve environmental cleaning and disinfection in a medical center.

Background: Inadequate hospital cleaning may contribute to cross-transmission of pathogens. It is important to implement effective cleaning for the safe hospital environment. We conducted a three-phase study using human factors engineering (HFE) approach to enhance environmental cleanliness. Methods: This study was conducted using a prospective interventional trial, and 28 (33.3%) of 84 wards in a medical center were sampled. The three-phases included pre-intervention analysis (Phase 1), implementing interventions by HFE principles (Phase 2), and programmatic analysis (Phase 3). The evaluations of terminal cleaning and disinfection were performed using the fluorescent marker, the adenosine triphosphate bioluminescence assay, and the aerobic colony count method simultaneously in all phases. Effective terminal cleaning and disinfection was qualified with the aggregate outcome of the same 10 high-touch surfaces per room. A score for each high-touch surface was recorded, with 0 denoting a fail and 10 denoting a pass by the benchmark of the evaluation method, and the total terminal cleaning and disinfection score (TCD score) was a score out of 100. Results: In each phase, 840 high-touch surfaces were collected from 84 rooms after terminal cleaning and disinfection. After the interventions, the TCD score by the three evaluation methods all showed significant improved. The carriage incidence of multidrug-resistant organism (MDRO) decreased significantly from 4.1 per 1000 patient-days to 3.6 per 1000 patient-days (P = .03). Conclusion: The HFE approach can improve the thoroughness and the effectiveness of terminal cleaning and disinfection, and resulted in a reduction of patient carriage of MDRO at hospitals. Larger studies are necessary to establish whether such efforts of cleanliness can reduce the incidence of healthcare-associated infection.

Chlorhexidine Bathing to Prevent Central Line-Associated Bloodstream Infections in Hematology Units: A Prospective, Controlled Cohort Study.

BACKGROUND: Chlorhexidine (CHG) bathing decreases the incidence of bloodstream infections in intensive care units, but its effect has been understudied in patients with hematological malignancies in noncritical care units. METHODS: Adults with hematological malignancies hospitalized for cytotoxic chemotherapy in noncritical care units were offered daily 2% CHG bathing. We compared outcomes of patients who chose CHG bathing (CHG group) with outcomes of those who did not choose CHG bathing (usual-care group). The primary outcome was gram-positive cocci-related, skin flora-related, or central line-associated bloodstream infection. The negative control outcome was gut-origin bacteremia. RESULTS: The CHG group (n = 485) had a crude incidence rate of the primary outcome that was 60% lower than the rate for the usual-care group (n = 408; 3.4 vs 8.4 per 1000 patient-days, P = .02) but had a similar crude incidence rate of the negative control outcome (4.5 vs 3.2 per 1000 patient-days; P = .10). In multivariable analyses, CHG bathing was associated with a 60% decrease in the primary outcome (adjusted hazard ratio [HR], 0.4; P < .001). In contrast, CHG bathing had no effect on the negative control outcome (adjusted HR, 1.1; P = .781). CHG bathing was well tolerated by participants in the CHG group. CONCLUSIONS: CHG bathing could be a highly effective approach for preventing gram-positive cocci-related, skin flora-related, or central line-associated bacteremia in patients with hematological malignancies who are hospitalized for cytotoxic chemotherapy in noncritical care units.

Comparative efficacy of doripenem versus meropenem for hospital-acquired and ventilator-associated pneumonia.

BACKGROUND: Doripenem shows good in vitro activity against common nosocomial pathogens, such as extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii. However, the use of doripenem for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) remains controversial. The aim of this study was to compare the efficacy and safety between doripenem and meropenem for patients with HAP or VAP. METHODS: Adult patients diagnosed with HAP and VAP at National Taiwan University Hospital, who received doripenem or meropenem for more than 48 h between January 2015 and November 2017, were retrospectively reviewed. All-cause mortality on the 30th day was used as the primary outcome measurements. RESULTS: Fifty-seven patients with doripenem and 252 patients with meropenem were analyzed. Compared to the meropenem group, the doripenem group was younger and had a higher Sequential Organ Failure Assessment (SOFA) score. Multivariable Cox regression analysis revealed that presence of solid organ malignancies (adjusted hazard ratio [AHR], 1.82; 95% CI, 1.04-3.19, p = 0.003) and SOFA score (AHR, 1.10; 95% CI, 1.03-1.17, p = 0.003) were independent factors associated with mortality. There was no survival difference of 30-day mortality between patients receiving doripenem and meropenem for HAP or VAP (log-rank p = 0.113). However, a poorer outcome was observed among patients with hematological disease in the doripenem group (log-rank p = 0.012). CONCLUSION: Our results demonstrate that doripenem has similar efficacy as meropenem in HAP or VAP patients. With an aim to enhance antibiotic diversity, doripenem could be an alternative choice for patients with HAP or VAP, except for those with hematological malignancies.

Community-acquired Legionnaires' disease at a medical center in northern Taiwan.

BACKGROUND/PURPOSE: Legionella pneumophila had been recognized as an important pathogen for community-acquired pneumonia. We aimed to investigate clinical features and outcomes of patients with Legionnaires' disease at a tertiary medical center in northern Taiwan. METHODS: From June 2012 to February 2017, a retrospective review of adult community-acquired. Legionnaires' disease at a medical center was conducted. All Legionella infections were confirmed by positive urinary Legionella antigen assay, sera indirect immunofluorescence assay, or sputum culture for Legionella. Literature review of Legionnaires' disease from Medline and PubMED websites was performed. RESULTS: A total of 32 cases of Legionnaires' disease were identified. Their mean age was 64.3 years, with male predominance (27 cases, 84.3%). The underlying diseases were varied and most were attributed to chronic disorders, such as diabetes mellitus (31%) and cigarette smoking (40.6%). The most common symptoms were cough (68%) and fever (59.3%). More than half of patients (18, 56.2%) with Legionnaires' disease could initially present with extrapulmonary manifestations. Sixteen (50%) patients had delay in initiation of appropriate antibiotic therapy. Patients without adequately initiation of appropriate antibiotic therapy had higher proportion (11 of 16, 68.7%) of intensive care unit admission than patients with adequate initiation (5 of 16, 31.2%). Our results inferred that a delay in treatment might result in worsening of disease severity and the need for more intensive management. Overall mortality rate was 21.8%. Development of vasopressor requirement is an independent risk factor associated with mortality. CONCLUSION: Legionnaires' disease in Taiwan frequently present with extrapulmonary manifestations. Patients with hemodynamic instability that need vasopressor therapy associated with mortality.

Effectiveness of echinocandins versus fluconazole for treatment of persistent candidemia: A time-dependent analysis.

OBJECTIVES: Echinocandins are fungicidal and more active than fluconazole against Candida biofilms. This is known to be an important mechanism for Candida persistence. However, there is limited evidence of effectiveness of echinocandins for treating persistent candidemia. METHODS: We prospectively observed adult patients with persistent candidemia from March 2011 to February 2016. This was defined as the isolation of the same Candida species for ≥ 5 days from blood cultures. We used a time-dependent analysis to evaluate the impact of definitive therapy on mycological eradication and overall survival at 30 days from the index date (the date of collecting the second positive blood culture). RESULTS: We screened 1162 episodes of candidemia. Of 196 non-duplicate patients enrolled, 64 received echinocandins and 132 received fluconazole as their first definitive therapy after the index date. The rates of mycological eradication and overall survival were 67.3% and 55.6%, respectively. The factors associated with mycological eradication included receipt of an echinocandin as the definitive therapy, adequate source control, and not receiving parenteral hyperalimentation. The factors related to overall survival were APACHE II, not receiving corticosteroids, and receiving cardiovascular or abdominal surgery. CONCLUSIONS: Echinocandins were more effective than fluconazole in achieving mycological eradication in patients with persistent candidemia.

Prevalence and characteristics of pks genotoxin gene cluster-positive clinical Klebsiella pneumoniae isolates in Taiwan.

The pks gene cluster encodes enzymes responsible for the synthesis of colibactin, a genotoxin that has been shown to induce DNA damage and contribute to increased virulence. The present study investigated the prevalence of pks in clinical K. pneumoniae isolates from a national surveillance program in Taiwan, and identified microbiological and molecular factors associated with pks-carriage. The pks gene cluster was detected in 67 (16.7%) of 400 isolates from various specimen types. Multivariate analysis revealed that isolates of K1, K2, K20, and K62 capsular types (p < 0.001), and those more susceptible to antimicrobial agents (p = 0.001) were independent factors strongly associated with pks-carriage. Phylogenetic studies on the sequence type (ST) and pulsed-field gel electrophoresis patterns indicated that the pks-positive isolates belong to a clonal group of ST23 in K1, a locally expanding ST65 clone in K2, a ST268-related K20 group, and a highly clonal ST36:K62 group. Carriage of rmpA, iutC, and ybtA, the genes associated with hypervirulence, was significantly higher in the pks-positive isolates than the pks-negative isolates (95.5% vs. 13.2%, p < 0.001). Further studies to determine the presence of hypervirulent pks-bearing bacterial populations in the flora of community residents and their association with different disease entities may be warranted.