Clonal aggregation of fluconazole-resistant Candida tropicalis isolated from sterile body fluid specimens from patients in Hefei, China.

Candida tropicalis, a human conditionally pathogenic yeast, is distributed globally, especially in Asia-Pacific. The increasing morbidity and azole resistance of C. tropicalis have made clinical treatment difficult. The correlation between clonality and antifungal susceptibility of clinical C. tropicalis isolates has been reported. To study the putative correlation in C. tropicalis isolated from normally sterile body fluid specimens and explore the distinct clonal complex (CC) in Hefei, 256 clinical C. tropicalis isolates were collected from four teaching hospitals during 2016-2019, of which 30 were fluconazole-resistant (FR). Genetic profiles of 63 isolates, including 30 FR isolates and 33 fluconazole-susceptible (FS) isolates, were characterized using multilocus sequence typing (MLST). Phylogenetic analysis of the data was conducted using UPGMA (unweighted pair group method with arithmetic averages) and the minimum spanning tree algorithm. MLST clonal complexes (CCs) were analyzed using the goeBURST package. Among 35 differentiated diploid sequence types (DSTs), 16 DSTs and 1 genotype were identified as novel. A total of 35 DSTs were assigned to five major CCs based on goeBURST analysis. CC1 (containing DST376, 505, 507, 1221, 1222, 1223, 1226, and 1229) accounted for 86.7% (26/30) of the FR isolates. However, the genetic relationships among the FS isolates were relatively decentralized. The local FR CC1 belongs to a large fluconazole non-susceptible CC8 in global isolates, of which the putative founder genotype was DST225. The putative correlation between MLST types and antifungal susceptibility of clinical C. tropicalis isolates in Hefei showed that DSTs are closely related to FR clones.

A local prevalent FR CC1, accounted for 86.7% of the FR isolates in Hefei, China, which showed that fluconazole resistance is closely related to the genetic background, a finding of great value to local medical treatment and possible reasons for the increase in azole resistance of Candida tropicalis.

Bloodstream Infections in Patients with Rectal Colonization by Carbapenem-Resistant Enterobacteriaceae: A Prospective Cohort Study.

Purpose: Carbapenem-resistant Enterobacteriaceae (CRE) infection has become a concerning threat, especially in hospital settings; however, its phenotypic characterization, association with rectal colonization and subsequent bloodstream infections (BSI) remain to be clarified. This study aimed to investigate the incidence and risk factors of CRE infection in rectal CRE carriers and to understand the clonality of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains and their association with subsequent BSI in these patients. Patients and Methods: This was a prospectively designed cohort study. Hospitalized patients treated at our institution from April 2019 to October 2020 with intestinal CRE carriage were screened at admission and weekly thereafter until death or discharge from the hospital. Stool and blood samples were obtained for strain growth and mass spectrometry. The colonization and clinical infection isolates were analyzed by antimicrobial susceptibility testing to identify CRE. The clonality of the CRE strains and their corresponding clinical infection strains was studied by whole-genome sequencing to explore the mechanism of drug resistance and evaluate possible transmission. CRE-associated risk factors were analyzed in combination with epidemiological data. Results: Of the 1203 patients, 85 were colonized by CRE and 21 developed CRE infection, of whom 13 developed CRE bloodstream infection (BSI). Ninety-one CRE strains were isolated from the rectal specimens of the 85 patients. Tracheotomy and chemotherapy in the past three months were independent risk factors for CRE infection in intestinal CRE carriers. ST11-KL64 (92.3%, 24/26) was the most dominant capsule and multilocus sequence typing (MLST) type among clonal CRKP isolates. Single-nucleotide polymorphism clustering showed homology of representative colonization and infection CRKP strain pairs (n=13) in the same patient. One group of leading clones was endemic in surgical intensive care units (ICUs). Twenty-four CRKP strains carried ß-lactamase K. pneumonia carbapenemase 2, and 73.1% (19 strains) of CRKP carried mucoid phenotype regulator genes A2 and iucABCD. Conclusion: In summary, intestinal CRE colonization was detectable at an elevated rate among hospitalized patients and prevalent in ICU patients, with potential rapid horizontal transmission, providing evidence that CRE BSI infection in hospitalized patients might be due to their colonized strains and indicates the correlation between intestinal colonization and BSI.

Systematic Characterization of Epidemiology, Antifungal Susceptibility, Risk Factors and Outcomes of Candidaemia: A Six-Year Chinese Study.

Background: Candida bloodstream infection (BSI), the fourth most common nosocomial BSI, is an urgent global health challenge with the tremendous growth in antifungal resistance rate and mortality rate. Purpose: To establish the epidemiology, species distribution, risk factors, and 30-day mortality of candidaemia among 115 patients in this 6-year surveillance study. Materials and Methods: We retrospectively analyzed the clinical characteristics, epidemiology, antifungal susceptibility patterns, and risk factors for morbidity and mortality of 115 candidaemia cases diagnosed in one tertiary care hospital from January 2016 through December 2021. Results: Of the 115 candidaemia cases, the most prevalent species were Candida tropicalis (33.0%), followed by Candida albicans (27.8%), Candida parapsilosis complex (19.1%), and others. The overall incidence was 0.21 cases/1000 admissions. The overall crude resistance rate of Candida spp. against azoles was 20.0% (23/115), while Candida tropicalis showed a significant increase in the resistance rate to azoles (from 1/6, 16.7% in 2017 to 6/10, 60.0% in 2021). Multivariate analyses demonstrated that hematological malignancy and neutropenia were significantly associated with Candida tropicalis BSI than Candida non-tropicalis BSI. Candida albicans BSI had a significantly higher rate of previous surgery than Candida non-albicans BSI. Candida parapsilosis BSI had a significantly higher rate of receiving total parenteral nutrition (TPN). The overall 30-day mortality rate was 27.0% (31/115). The presence of high age-adjusted Charlson comorbidity index (aCCI), neutropenia, and septic shock were factors independently associated with increased 30-day mortality. Conclusion: Candida tropicalis are emerging as the predominant isolate in candidaemia. Of note, the unexpectedly increased resistance rate to azoles in Candida tropicalis BSI was observed. The aCCI scores, neutropenia, and septic shock were independently associated with 30-day mortality. Prompt, adequate antifungal treatment among high-risk patients may lead to a reduction in mortality.

Gilbert syndrome with systemic lupus erythematosus presenting with persistent unconjugated hyperbilirubinemia: A case report.

Gilbert syndrome (GS) is a hereditary unconjugated hyperbilirubinemia that results from mutations in the bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1) gene. To the best of our knowledge, there are currently no reports that focus on patients with systemic lupus erythematosus (SLE) coexisting with GS. The present study aimed to evaluate the clinical characteristics and genotype of UGT1A1 in a Chinese patient with SLE and GS. Complete medical records and laboratory data were reviewed for a patient with SLE referred to Ruijin Hospital (Shanghai, China) for treatment between March 2016 and January 2020. Genetic analysis of the UGT1A1 gene was performed by PCR amplification and Sanger sequencing. The serum total bilirubin and unconjugated bilirubin concentrations on admission were 96.2 and 86.8 µmol/l, respectively. The homozygous mutation c.1456T>G (p.Y486D) in exon 5 was detected in this patient. The patient had a good response to phenobarbital orally at a dose of 30 mg/day and a decrease in serum bilirubin was observed. Elevated unconjugated hyperbilirubinemia in SLE needs to be differentiated from other diseases, such as GS, which can be diagnosed by UGT1A1 genetic sequencing.

Evaluation of analytic and clinical performance of thrombin-antithrombin complex and D-dimer assay in prognosis of acute ischemic stroke.

: To evaluate analytic and clinical performance of plasma thrombin-antithrombin complex (TAT) and D-dimer assay in assessing the severity and outcome of acute ischemic stroke. The prospective study was conducted and extended from January 2018 to December 2018. A total of 236 patients admitted within 24 h after neurologic symptoms onset were recruited. The median TAT and D-dimer levels were significantly higher in the acute ischemic stroke patients than in the controls. The average TAT levels in patients with mild, moderately severe and severe stroke were 1.75 [interquartile ranges (IQR), 1.1-2.6], 3.3 (IQR, 1.8-4.5) and 13.5 (IQR, 7.2-15.3) ng/ml. The D-dimer levels of respective patient groups were 0.39 (IQR, 0.22-0.73), 0.58 (IQR, 0.39-1.25) and 3.59 (IQR, 1.73-4.74) mg/l. With the optimal cut-off TAT level (1.75 ng/ml) determined from receiver operating characteristic analysis, the Area under the curve (AUC), the sensitivity and specificity of TAT for stroke diagnosis were 0.763, 58.1 and 87.8%. The cut-off D-dimer level was 0.38 mg/l and the AUC, the sensitivity and specificity were 0.772, 60.2 and 88.9%. The Area under the receiver operating characteristic curves (AUROCs) and sensitivity in the moderate to severe stroke increased to 0.903 and 86.9% for TAT, and 0.880 and 80.3% for D-dimer, respectively. Age and high TAT level were significant independent risk factors for stroke severity. Age, high initial National Institutes of Health Stroke Scale score and high TAT level were significant independent poor prognostic factors on multivariate analysis. TAT and D-dimer were superior in separating the moderate-to-severe stroke than mild stroke. A high TAT plasma level is an independent predictor for stroke severity and poor prognosis during 1-month follow-up.

Inhibitor eradication and bleeding management of acquired hemophilia A: a single center experience in China.

Objectives: Acquired hemophilia A (AHA) is a rare disease resulting from autoantibodies against coagulation factor VIII that leads to spontaneous bleeding. This study reports the clinical characteristics and treatment outcomes of a relatively sizable cohort of patients with AHA. Methods: We retrospectively analyzed the characteristics and outcomes of 42 patients with AHA diagnosed in our center from January 2014 through December 2018. Results: The FVIII activity (FVIII: C) was significantly suppressed (median 1.5%; interquartile range [IQR]: 0.9-3.5) by FVIII inhibitor (median 8 BU/mL; IQR: 4.0-16.0). Bypassing agents, PCC or FVIIa, were used in 14 patients for bleeding control without any adverse reaction; and most patients (90.5%, 38/42) were placed on immunosuppressive regimen, corticosteroid alone or in combination with cyclophosphamide. Patients treated with corticosteroids alone had a lower median inhibitor titer (8 BU/mL) than those treated with combination corticosteroids of cyclophosphamide (16 BU/mL) (p < 0.001). 97.4% (37/38) patients achieved complete remission (CR) after immunosuppression therapy, and the median time to CR in patients treated with corticosteroids alone was shorter than those with combination corticosteroids of cyclophosphamide (median 40 days; IQR: 31-65 vs. 51 days; IQR: 38-83, p = 0.301). 10 (26.3%) patients relapsed thereafter and were placed on combined corticosteroid and cyclophosphamide treatment, which yielded second remission in 8 patients (80%). Two patients died, one from uncontrolled post-surgical retroperitoneal hemorrhage and one from sepsis complicating corticosteroid therapy. Conclusion: The corticosteroid achieves a satisfactory outcome, particularly with low inhibitors titers; and combination of cyclophosphamide will facilitate remission in sever patients with high titers of inhibitors.

Use of MALDI-TOF MS for Rapid Identification of Clinical Bacterial Strains that Are Uncommon or Difficult to Identify.

The purpose of this investigation was to evaluate the analytical and practical performance of MALDI-TOF MS for the identification of clinical uncommon or difficult-to-identify bacteria. A total of 180 clinical isolates collected from January 2014 to December 2016, were identified by MALDI-TOF MS and Vitek2 Compact using 16S rRNA gene sequence analysis as the gold method. For MALDI-TOF MS, 152(84.4%) isolates were correctly identified to the species level, 23(12.8%) isolates were identified to the genus level only, 3(1.7%) were misidentified and 2(1.1%) were unidentified. Compared to those obtained by Vitek2 Compact, 128(71.1%) isolates were correctly identified to the species level, 11(6.1%) isolates were identified to the genus level only, 11(6.1%) were misidentified and 30(16.7%) were unidentified. Vitek2 Compact and MALDI-TOF MS accurately identified 71.1%(128/180), 84.4%(152/180) of the isolates. The time required for the identification by MALDI-TOF MS, Vitek2 Compact, and 16S rRNA gene sequencing was about 10min/strain, 8~12 h/strain and 10 h/ strain. MALDI-TOF MS can be the powerful tools for fast and accurate identification of clinical uncommon or difficult-to-identify bacteria.