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Neutrophils play essential anti-microbial and inflammatory roles in host defense, however their activities are tightly regulated as neutrophil dysfunction often leads to detrimental inflammatory and autoimmune diseases. Here, we identified a novel PR3/CD177/GPR97/PAR2/CD16b interactome as a critical modulator of neutrophil activation. Using multiple approaches, we deorphanized GPR97, a human neutrophil-restricted adhesion G protein-coupled receptor (aGPCR), as the interacting protein and allosteric activator of CD177-associated membrane proteinase 3 (mPR3). Structural and deletion analysis of the GPR97 extracellular region disclosed two independent mPR3-binding domains. The efficient binding and activation of mPR3 by GPR97 required a macromolecular CD177/GPR97/PAR2/CD16b interactome and resulted in the transactivation of PAR2, another GPCR. GPR97-mediated PAR2 transactivation in neutrophils elicited strong inflammatory activation, triggering anti-microbial activities and endothelial dysfunction. Altogether, we identify a novel aGPCR-GPCR transactivation mechanism that directs neutrophil activation and inflammation. The PR3/CD177/GPR97/PAR2/CD16b interactome represents a potential therapeutic target for neutrophil-mediated inflammatory diseases.

Phaeohyphomycosis is a term used to describe a heterogenous group of cutaneous and systemic mycotic infections caused by melanized fungi. Many fungi have been reported as pathogens of this disease. The disease spectrum ranges from superficial cutaneous infections, deep cutaneous infections, to systemic infections with internal organ involvement. We report two cases of deep cutaneous phaeohyphomycosis on the foot clinically presenting as cellulitis with abscess formation. The pathogens were isolated from the lesion and both were identified as Neoscytalidium dimidiatum by their colony morphology, microscopic features, and sequences of internal transcribed spacers of ribosomal DNA. Both patients did not respond to the therapy with voriconazole and itraconazole, but improved after intravenous amphotericin B.

Background/purpose Superspreading events (SSEs) are pivotal in the spread of SARS-CoV-2. This study aimed to investigate an SSE of COVID-19 in a hospital and explore the transmission dynamics and heterogeneity of SSE. Methods We performed contact tracing for all close contacts in a cluster. We did nasopharyngeal or throat swabbing for SARS-CoV-2 by real-time RT-PCR. Environmental survey was performed. The epidemiological and clinical characteristics of the SSE were studied. Results Patient 1 with congestive heart failure and cellulitis, who had onset of COVID-19 two weeks after hospitalization, was the index case. Patient 1 led to 8 confirmed cases, including four health care workers (HCW). Persons tested positive for SARS-CoV-2 were HCW (n = 4), patient 1's family (n = 2), an accompanying person of an un-infected in-patient (n = 1), and an in-patient admitted before the SSE (n = 1). The attack rate among the HCW was 3.2 % (4/127). Environmental survey confirmed contamination at the bed rails, mattresses, and sink in the room patient 1 stayed, suggesting fomite transmission. The index case's sputum remained positive on illness day 35. Except one asymptomatic patient, at least three patients acquired the infection from the index case at the pre-symptomatic period. The effective reproduction number (Rt) was 0.9 (8/9). Conclusion The host factor (heart failure, longer viral shedding), transmissibility of SARS-CoV-2 (Rt, pre-symptomatic transmission), and possible multiple modes of transmission altogether contributed to the SSE. Rapid response and advance deployment of multi-level protection in hospitals could mitigate COVID-19 transmission to one generation, thereby reducing its impact on the healthcare system.

Background Effective ART is crucial for combating the HIV pandemic. Clinically, plasma viral load monitoring to achieve virological suppression is the guide for an optimal ART. The presence of low-level viraemia (LLV) below the definition level of virological failure is a risk factor for ART failure. However, there is no treatment consensus over LLV yet, mainly due to the limitation of standard HIV-RNA genotyping and the resultant insufficient understanding of LLV characteristics. Objectives To better profile drug resistance mutations (DRMs) and the associated factors in cases experiencing LLV. Methods A prospective observational study was conducted from 2017 to 2019. HIV-DNA was used as an alternative to HIV-RNA for HIV genotyping coupled with deep sequencing for ART-naive and ART-failure cases, as well as those with LLV. Results Eighty-one ART-naive, 18 ART-failure and 16 LLV cases received HIV genotyping in the study. Three-quarters (12/16) of cases experiencing LLV harboured DRMs. Cases with LLV had higher prevalence of DRMs to NNRTIs than the ART-naive group (69% versus 20%, P Conclusions HIV DRM profiles in LLV cases were significantly different to those in ART-naive and ART-failure cases. Approaches to consolidate ART compliance and early exploration of potential ART resistance may be needed for cases experiencing LLV episodes.

Candida albicans bloodstream infection (BSI) is epidemiologically important because of its increasing frequency and serious outcome. Strain typing and delineation of the species are essential for understanding the phylogenetic relationship and clinical significance. Microsatellite CAI genotyping and multilocus sequence typing (MLST) were performed on 285 C. albicans bloodstream isolates from patients in Chang Gung Memorial Hospital at Linkou (CGMHL), Taiwan from 2003 to 2011. Data regarding demographics, comorbidities, risk factors, and clinical outcomes were recorded within adult patients with C. albicans BSI. Both CAI genotyping and MLST yielded comparable discriminatory power for C. albicans characterization. Besides, the distribution of CAI repetition showed a satisfactory phylogenetic association, which could be a good alternative method in the molecular phylogenetics of C. albicans and epidemiological studies. As for the clinical scenario, clade 17 isolates with CAI alleles either possessing 29 or more repetitions were related to higher 14-day and 30-day mortality, and shorter median survival days.

Based on multiple locus sequence typing, we previously found that DST659 and DST693 were dominant genotypes of Candida albicans among the bloodstream isolates at Chang-Gung Memorial Hospital at Linkou. Biofilm-forming activity, which is critical for C. albicans virulence, probably contributed to the dominance of antifungal sensitive isolates in hospital. Both in vitro membrane weighting and in vivo zebrafish egg infection assays were used to evaluate the biofilm-forming activity of DST659 and DST693 genotypes. Medical records of the patients infected by these two genotypes were retrospectively reviewed. High biofilm-forming activity of DST659 isolates was demonstrated in vitro and further proved with the zebrafish egg infection model, which showed a positive correlation between the biofilm-forming extent on chorion and the in vitro biofilm activity. Moreover, significantly less embryos survived when infected with DST659 isolates than those with DST693 (1.25% vs. 11.43%), and the high-biofilm subset of DST659 showed a greater reduction in survival of embryos at 48 h post-infection than the low-biofilm subset (0 vs. 1.92%). Patients infected with DST659 seemed to survive slightly worse than those infected with DST693, although the difference was insignificant. It is noteworthy that DST659-infected patients were associated with a higher incidence in renal insufficiency as compared to those with DST693, the low biofilm genotype. We suggest that a strong biofilm activity of DST659 contributed to a high mortality rate in zebrafish hosts and poor renal function in patients, as well as gaining the dominance in the northern Taiwan.

To investigate the risk factors and outcomes associated with Candida parapsilosis candidemia, a retrospective study was conducted at a tertiary medical center in northern Taiwan. Patients with C. parapsilosis candidemia and corresponding controls with C. albicans candidemia were chosen and their demographics, comorbidities, risk factors, and clinical outcomes were reviewed. Antifungal susceptibility tests were performed using the Sensititre YeastOne colorimetric system. Matrix-assisted laser desorption ionization-time of flight mass spectrometry was used to classify the genomic species. Of the 270 candidemias found in 253 patients, C. albicans was the most common Candida species isolated (43.0%), followed by C. parapsilosis (22.6%), C. tropicalis (17.4%), and C. glabrata (10.0%). The 30-day mortality of C. parapsilosis candidemia was significantly lower than that of C. albicans candidemia (21.7% vs. 53.9%, P

Introduction The prognostic value of epidermal growth factor receptor (EGFR) mutations and the correlation between EGFR mutations and the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) histological classification remain controversial. The current study aimed to investigate the pure prognostic role of EGFR mutations in treatment-naive patients with resected stage I lung adenocarcinoma. Methods We retrospectively reviewed 373 patients with stage I pulmonary non-small-cell lung cancer who underwent complete surgical resection between January 2010 and May 2014. The tumors were classified according to IASLC/ATS/ERS criteria. EGFR mutation status was determined by established methods. Results A total of 120 patients were included for analysis; 87 had tumors with EGFR mutations and 33 had wild-type tumors. More low- and intermediate-grade tumors had EGFR mutations, and nearly half of the high-grade tumors were wild-type (75.7% versus 46.2%, p = 0.041). Patients with low-grade tumors had significantly greater median disease-free survival (DFS) (76.8 versus 13 months, p < 0.0001) and better overall survival (OS) (median OS not reached, p = 0.0003) than those with intermediate- and high-grade tumors. Tumor recurrence was 41.4% and 30.3% in mutant and wild-type patients. The 5-years survival rate was 54% and 71.2%. Multivariate analysis revealed that the new histological classification and the pathologic stage were independent predictors of both DFS and OS. EGFR mutation status had no prognostic implications. Conclusion Low grade tumors according to IASLC/ATS/ERS histological classification and the pathologic stage IA tumors of resected stage I lung adenocarcinomas independently predict better DFS and OS. EGFR mutations were frequently seen in histologically low- and intermediate-grade tumors but not a prognostic factor.

Taking antibiotics in strict adherence to physician prescriptions is crucial for maintaining the stability of the drug concentration in the blood and for achieving the best therapeutic effects. The increasing antimicrobial resistance in recent decades has led the Ministry of Health and Welfare to promote the rational use of antibiotics and the use of a computer monitoring system to control the use of antibiotics in hospitals. Although non-adherence is considered as the major factor contributing to antimicrobial resistance, patient non-adherence to antibiotic prescriptions is an issue that has been largely overlooked. This paper explores this issue due to the serious threat from antimicrobial resistance and the few studies that have investigated patient adherence to antibiotic treatments for acute infections in Taiwan.The aims of the study include: (1) describe patient's adherence to antibiotic therapy for acute infections and (2) explore the potential factors of influence on antibiotic adherence such as demographics, disease characteristics, and knowledge of antibiotic treatment.The study used a descriptive correlational design. A convenience sample of 162 patients with acute infections was recruited from outpatient infectious disease clinics in Taoyuan City. Data were collected using the study questionnaire and analyzed using the chi-square test, Mann-Whitney U test, and logistic regression.The study results showed that only 40.1% of patients followed their prescription to take antibiotics completely. The remainder earned lower scores than their prescription-adhering counterparts for knowledge regarding the effects of antibiotics (U = 2654.5, p = .046). Results of logistic regression showed that knowledge regarding the effects of antibiotics was the most significant predictor (B = .481, p = .046) of adherence to antibiotic therapies.Non-adherence to prescriptions is prevalent in short-term antibiotic treatments prescribed for acute infections. This finding reminds healthcare providers to provide proper education to the recipients of antibiotic treatments, even those treated for a very short duration for acute infections in outpatient settings. Special attention should be pay to enhancing the understanding and appreciation of patients for the therapeutic effects of antibiotics.急性感染病人抗生素服藥遵從性及其影響因素之研究服用抗生素的時間和劑量要符合醫師處方才能維持穩定的藥物血中濃度，進而發揮最佳滅菌或抑菌的效果與減少產生細菌抗藥性的機會。有鑑於抗藥性菌種問題日益嚴重，衛生服利部在醫院中積極推動抗生素使用的合理性、電腦管制抗生素的使用量等，卻忽略了門診病人在抗生素的使用上是否正確，國外研究顯示抗生素服藥不遵從是導致抗藥性菌種問題的主因之一，然而台灣關於抗生素服藥遵從性的研究少，且抗藥性菌種問題嚴重，故引發作者探討感染科門診就診之急性感染病人服用抗生素的遵從性及其影響因素之動機，以作為日後改善抗生素服藥遵從性的參考。本研究目的為(1)描述急性感染門診病人服用抗生素的遵從情形，(2)探討影響服用抗生素遵從性的因素，包括人口學、疾病特性與抗生素服藥知識。採描述性相關研究設計，以因急性感染服用抗生素之門診病人為研究對象，採方便取樣，共招募162位符合收案條件之病人參與本研究，以結構式問卷進行資料收集，以Chi-square test、Mann-Whitney U test和logistic regression進行資料分析。研究結果顯示因急性感染接受抗生素短期治療之門診病人按醫囑服用抗生素的遵從度不高，在平均5天的抗生素療程中，僅有40.1%的病人完全遵從醫囑服用抗生素。不遵從者在抗生素效果面向的知識得分較遵從者低（U = 2654.5, p = .046）。邏輯式回歸結果顯示抗生素效果面向的知識為不遵從服藥的重要預測子（B = .481, p = .046）。不同於醫護人員的預期，因急性感染接受短期抗生素治療的病人，未遵從醫囑服藥的情形是很普遍的。此一發現提醒醫護人員即便是治療因急性感染短期接受抗生素治療之門診病人，亦應加強抗生素相關衛教，特別是抗生素效果面向有關的抗生素知識，進而增加病人之服藥遵從性。

Background/Purpose Serratia marcescens is a rare pathogen of central nervous system infections. This study was to investigate the epidemiology, prognostic factors, and treatment outcomes of S. marcescens meningitis. Methods This retrospective analysis included 33 patients with culture-proven S. marcescens meningitis hospitalized between January 2000 and June 2011. Results Of the 33 patients enrolled, only one did not receive neurosurgery before the onset of S. marcescens meningitis. Patients with S. marcescens meningitis had higher ratios of brain solid tumors (54.5%) and neurosurgery (97.0%) with a mortality rate of 15.2%. The mean interval between the first neurosurgical procedure and the diagnosis of meningitis was 17.1 days (range, 4–51 days). Only one third-generation cephalosporin-resistant S. marcescens isolate was recovered from the patients' cerebrospinal fluid (CSF) specimens. Compared with the favorable outcome group ( n = 20), the unfavorable outcome group ( n = 13) had a higher percentage of brain solid tumors, more intensive care unit stays, and higher Sequential Organ Failure Assessment score, CSF lactate and serum C-reactive protein concentrations at diagnosis of meningitis. Under the multiple regression analysis, CSF lactate concentration ≥2-fold the upper limit of normal (ULN) was independently associated with unfavorable outcomes (odds ratio, 7.20; 95% confidence interval, 1.08–47.96; p = 0.041). Conclusion S. marcescens meningitis is highly associated with neurosurgical procedures for brain solid tumors. CSF lactate concentration ≥2x ULN may predict an unfavorable outcome. Its mortality is not high and empiric treatment with parenteral third-generation cephalosporins may have a satisfactory clinical response.

Background The treatment options for pneumonia involving multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (MDR Acb) complex are limited, and the optimal treatment has not been established. Methods To compare the efficacy of tigecycline-based with sulbactam (or ampicillin/sulbactam)-based therapy for pneumonia involving MDR Acb complex, we conducted a retrospective study comparing 84 tigecycline-treated adult patients during the period August 2007 to March 2010 with 84 sulbactam or ampicillin/sulbactam-treated adult patients during the period September 2004 to July 2007. Both groups had the matched Acute Physiology and Chronic Health Evaluation (APACHE) II score and received treatment for at least 7 days. Results The mean APACHE II score was 20.1 for both groups. More patients in sulbactam group had ventilator use (89.3 % versus 69.0 %), bilateral pneumonia (79.8 % versus 60.7 %) and combination therapy (84.5 % versus 53.6 %), particularly with carbapenems (71.4 % versus 6.0 %), while more patients in tigecycline group had delayed treatment (41.7 % versus 26.2 %) (P