The first case of subcutaneous mycosis caused by Muyocopron laterale in China.

Muyocopron laterale is a type of endophytic fungus that parasitizes monocotyledonous plants. Cases of humans and other mammals being infected by M. laterale are very rare around the world. We report the first case of subcutaneous mycosis caused by M. laterale in China. A kidney transplant recipient was admitted for Pneumocystis carinii pneumonia and subsequently developed left calf redness and swelling due to a M. laterale infection. The patient was treated with sulfamethoxazole and voriconazole and underwent five surgical debridements and vacuum sealing drainage (VSD) applications with the left leg. The patient was eventually cured and discharged from the hospital.

Binding characteristics of pheromone-binding protein 1 in Glyphodes pyloalis to organophosphorus insecticides: Insights from computational and experimental approaches.

Glyphodes pyloalis (Lepidoptera: Pyralidae) is one of the major pests in mulberry production in China, which has developed resistance to various insecticides. Chemoreception is one of the most crucial physiological tactics in insects, playing a pivotal role in recognizing chemical stimuli in the environment, including noxious stimuli such as insecticides. Herein, we obtained recombinant pheromone-binding protein 1 (GpylPBP1) that exhibited antennae-biased expression in G. pyloalis. Ligand-binding assays indicated that GpylPBP1 had the binding affinities to two organophosphorus insecticides, with a higher binding affinity to chlorpyrifos than to phoxim. Computational simulations showed that a mass of nonpolar amino acid residues formed the binding pocket of GpylPBP1 and contributed to the hydrophobic interactions in the bindings of GpylPBP1 to both insecticides. Furthermore, the binding affinities of three GpylPBP1 mutants (F12A, I52A, and F118A) to both insecticides were all significantly reduced compared to those of the GpylPBP1-wild type, suggesting that Phe12, Ile52, and Phe118 residues were crucial binding sites and played crucial roles in the bindings of GpylPBP1 to both insecticides. Our findings can be instrumental in elucidating the effects of insecticides on olfactory recognition in moths and facilitating the development of novel pest management strategies using PBPs as targets based on insect olfaction.

Survival analysis and nomogram for pulmonary sarcomatoid carcinoma: an SEER analysis and external validation.

OBJECTIVE: Uncommon and particularly deadly, pulmonary sarcomatoid carcinoma (PSC) is an aggressive type of lung cancer. This research aimed to create a risk categorisation and nomogram to forecast the overall survival (OS) of patients with PSC. METHODS: To develop the model, 899 patients with PSC were taken from the Surveillance, Epidemiology, and End Results database from the USA. We also used an exterior verification sample of 34 individuals with PSC from Fujian Provincial Hospital in China. The Cox regression hazards model and stepwise regression analysis were done to screen factors in developing a nomogram. The nomogram's ability to discriminate was measured employing the area under a time-dependent receiver operating characteristic curve (AUC), the concordance index (C-index) and the calibration curve. Decision curve analysis (DCA) and integrated discrimination improvement (IDI) were used to evaluate the nomogram to the tumour-node-metastasis categorisation developed by the American Joint Committee on Cancer (AJCC-TNM), eighth edition, and an additional sample confirmed the nomogram's accuracy. We further developed a risk assessment system based on nomogram scores. RESULTS: Six independent variables, age, sex, primary tumour site, pathological group, tumour-node-metastasis (TNM) clinical stage and therapeutic technique, were chosen to form the nomogram's basis. The nomogram indicated good discriminative ability with the C-index (0.763 in the training cohort and 0.746 in the external validation cohort) and time-dependent AUC. Calibration plots demonstrated high congruence between the prediction model and real-world evidence in both the validation and training cohorts. Nomogram outperformed the AJCC-TNM eighth edition classification in both DCA and IDI. Patients were classified into subgroups according to their risk ratings, and significant differences in OS were observed between them (p<0.001). CONCLUSION: We conducted a survival analysis and nomogram for PSC. This developed nomogram holds potential to serve as an efficient tool for clinicians in prognostic modelling.

Pseudomonas aeruginosa High-Risk Sequence Type 463 Co-Producing KPC-2 and AFM-1 Carbapenemases, China, 2020-2022.

We report the clonal spread and evolution of high-risk Pseudomonas aeruginosa sequence type 463 co-producing KPC-2 and AFM-1 carbapenemases isolated from hospital patients in China during 2020-2022. Those strains pose a substantial public health threat and surveillance and stricter infection-control measures are essential to prevent further infections.

Risk factors and outcomes of inpatients with carbapenem-resistant Pseudomonas aeruginosa bloodstream infections in China: a 9-year trend and multicenter cohort study.

Objective: Bacteremia caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) has high mortality, threatening the healthcare quality worldwide. Analysis is required to update the epidemiological data of CRPA bloodstream infections (BSI) and evaluate the prevalent strains in China. Moreover, it is necessary to clarify the risk factors associated with the development and mortality of CRPA bacteremia. Methods: This is a 9-year multicenter retrospective study, enrolling 137 patients with CRPA BSI and 137 carbapenem-susceptible P. aeruginosa (CSPA) BSI during January 2012 and December 2020. Antimicrobials susceptibility between the two groups were compared. Risk factors of CRPA BSI were identified by binary logistic regression for development and cox regression for mortality. The Kaplan-Meier method was used to compare time to mortality. CRPA and difficult-to-treat resistant P. aeruginosa (DTRPA) detection rate was analyzed year-by-year in ZYH. Results: A total of 7,384 P. aeruginosa clinical samples were cultured in ZYH during 9 years, and notable increase of CRPA and DTRPA detection rate in P. aeruginosa BSI was identified (from 17 to 60%; from 2.1 to 25%). Multivariate analysis revealed that prior ICU hospitalization, immunosuppressive therapy and exposure to carbapenems were independent risk factors for development of CRPA BSI. The 30-day crude mortality of 137 CRPA BSI was 39%. A total of 46 DTRPA were identified, and the 30-day mortality for patients infected by DTRPA was 50%. The 30-day crude mortality of CRPA BSI was independently associated with multiple organ failure and higher Pitt bacteremia score, whereas receipt appropriate therapy improved prognosis. Conclusion: A significant increase in the detection rate of CRPA and DTRPA in P. aeruginosa BSI was identified. Strict policies for carbapenems usage, cautious decisions regarding the usage of immunosuppressive agent and standard care for patients with prior ICU hospitalization are necessary for CRPA BSI management.

Odorant-Binding Protein 6 Contributes High Binding Affinity to Insecticides in a Parasitic Wasp Meteorus pulchricornis (Hymenoptera: Braconidae).

Meteorus pulchricornis is a preponderant parasitic wasp of various lepidopteran pests. The extensive application of broad-spectrum insecticides usually causes serious threats to the olfactory recognition of nontarget insects such as parasitoid wasps. However, the binding mechanism of odorant-binding proteins (OBPs) to insecticides in parasitoid wasps remains unknown. Herein, we find that the MpulOBP6 protein had a strong binding affinity to three insecticides (phoxim, chlorpyrifos, and chlorfenapyr). Results of computational simulations revealed that the hydrophobic interaction contributed by a mass of nonpolar amino acid residues was the primary driving force in the formation and stabilization of MpulOBP6-insecticide complexes. Among them, four residues (Met75, Val84, Phe121, and Pro122) and two residues (Val84 and Phe111) play an essential role in the binding of MpulOBP6 to phoxim and chlorfenapyr, respectively. Our findings could be instrumental to elucidate the effects of insecticide application toward the olfactory recognition of nontarget insects in the processes of agricultural production.

In vivo acquisition of blaKPC-2 with low biological cost in blaAFM-1-harboring ST463 hypervirulent Pseudomonas aeruginosa from a patient with hematologic malignancy.

OBJECTIVES: Klebsiella pneumoniae carbapenemase (KPC)-producing sequence type (ST) 463 Pseudomonas aeruginosa are increasingly prevalent in China. This study aims to investigate how blaKPC-2 is acquired in ST463 P. aeruginosa during antimicrobial therapy. METHODS: Two extensively drug-resistant P. aeruginosa strains, B1122 and U1121, were respectively isolated from blood and urine of a patient during carbapenem therapy. Whole-genome sequences were obtained, and minimum inhibitory concentrations (MICs) were determined. Plasmid transferability and stability were examined. Bacterial growth kinetics, biofilm formation, and virulence level was assessed. RESULTS: U1121 and B1122 were only susceptible to amikacin and intermediately susceptible to colistin. They were isogenic ST463 P. aeruginosa strains and shared the same chromosome-encoded resistance genes, including blaAFM-1. This is the first report of chromosomal integration of blaAFM-1 in P. aeruginosa mediated by ISCR29. pU1121 and pB1122, which shared almost identical backbone, were the sole plasmids in U1121 and B1122, respectively, differing by an insertion region containing two copies of blaKPC-2 genes observed on pU1121. Sequence alignment revealed that pU1121 might evolve in vivo from pB1122 via IS26-mediated continuous genetic rearrangement in response to selective challenge from carbapenem. pU1121 was not self-transmissible and could be stably maintained in the host in the absence of antibiotic. Both U1121 and B1122 were hypervirulent, and no differences on virulence were recorded between them. However, U1121 exhibited significant impaired growth in comparison with B1122. CONCLUSION: ST463 P. aeruginosa can capture blaKPC-2 through horizontal transfer of insertion sequence under antibiotic selection pressure, which does decrease the fitness but does not impair the virulence of the ancestor.

Pyogenic liver abscess-caused Klebsiella pneumoniae in a tertiary hospital in China in 2017: implication of hypervirulent carbapenem-resistant strains.

BACKGROUND: To investigate the epidemiology of Klebsiella pneumoniae (K. pneumoniae) inducing pyogenic liver abscess (PLA) in east China and the role of hypervirulent carbapenem-resistant K. pneumoniae (Hv-CRKP). METHODS: Forty-three K. pneumoniae strains were collected from 43 patients with PLA at Hangzhou, China in 2017. Antimicrobial susceptibility tests, string test, multilocus sequence typing, pulsed-field gel electrophoresis, mobile genetic elements typing, regular PCR and sequencing, and Galleria mellonella (G. mellonella) lethality test were used to elucidate the epidemiology. Clinical data were collected. RESULTS: K. pneumoniae strains with serotypes K1 and K2 accounted for 69.8%, which shared 46.5% and 23.3% respectively. K. pneumoniae strains with clonal group 23 were predominant with a rate of 34.9%. Such antimicrobials showed susceptible rates over 80.0%: cefuroxime, cefotaxime, gentamycin, ticarcillin/clavulanate, ceftazidime, cefoperazone/tazobactam, cefepime, aztreonam, imipenem, meropenem, amikacin, tobramycin, ciprofloxacin, levofloxacin, doxycycline, minocycline, tigecycline, chloramphenicol, and trimethoprim-sulfamethoxazole. PFGE dendrogram showed 29 clusters for the 43 K. pneumoniae strains. Three Hv-CRKP strains were confirmed by G. mellonella lethality test, showing a constituent ratio of 7.0% (3/43). Totally three deaths were found, presenting a rate of 7.0% (3/43). The three died patients were all infected with Hv-CRKP. CONCLUSIONS: K1 and K2 are the leading serotypes of K. pneumoniae causing PLA, which show highly divergent genetic backgrounds. Aminoglycosides, Generation 2nd to 4th cephalosporins, ß-lactamase/ß-lactamase inhibitors, carbapenems, fluoroquinolones are empirical choices. Hv-CRKP may confer an urgent challenge in the future.

Development and validation of a deep learning model to predict survival of patients with esophageal cancer.

Objective: To compare the performance of a deep learning survival network with the tumor, node, and metastasis (TNM) staging system in survival prediction and test the reliability of individual treatment recommendations provided by the network. Methods: In this population-based cohort study, we developed and validated a deep learning survival model using consecutive cases of newly diagnosed stage I to IV esophageal cancer between January 2004 and December 2015 in a Surveillance, Epidemiology, and End Results (SEER) database. The model was externally validated in an independent cohort from Fujian Provincial Hospital. The C statistic was used to compare the performance of the deep learning survival model and TNM staging system. Two other deep learning risk prediction models were trained for treatment recommendations. A Kaplan-Meier survival curve was used to compare survival between the population that followed the recommended therapy and those who did not. Results: A total of 9069 patients were included in this study. The deep learning network showed more promising results in predicting esophageal cancer-specific survival than the TNM stage in the internal test dataset (C-index=0.753 vs. 0.638) and external validation dataset (C-index=0.687 vs. 0.643). The population who received the recommended treatments had superior survival compared to those who did not, based on the internal test dataset (hazard ratio, 0.753; 95% CI, 0.556-0.987; P=0.042) and the external validation dataset (hazard ratio, 0.633; 95% CI, 0.459-0.834; P=0.0003). Conclusion: Deep learning neural networks have potential advantages over traditional linear models in prognostic assessment and treatment recommendations. This novel analytical approach may provide reliable information on individual survival and treatment recommendations for patients with esophageal cancer.

Hemophagocytic Lymphohistiocytosis Secondary to Disseminated Histoplasmosis in HIV Seronegative Patients: A Case Report and Review of the Literature.

Hemophagocytic lymphohistiocytosis (HLH) secondary to Histoplasma capsulatum infection is a rare disorder with poor outcome. Although cases of patients with human immunodeficiency virus (HIV) infection have been well documented, little study has reported in the setting of HIV seronegative. In this study, we report a case of HLH secondary to histoplasmosis in an immunocompetent patient in China and review all cases on this situation. The objective was to summary their epidemiology, clinical characteristics, diagnostic approaches, and therapeutic response. A 46-year-old male cooker presented fever, fatigue, anorexia, and weight loss. Bone marrow examination suggest fungus organism and hemophagocytosis, and further, bone marrow culture confirmed Histoplasma capsulatum, as the etiology of HLH. The patient was successfully treated. We reviewed a total of the 13 cases (including our patient) of HLH with histoplasmosis in intact immunology patients. Twelve of the 13 patients are from endemic areas, and nine of the 12 cases are from emerging endemic areas, India and China. Three patients had sojourn history may related to the disease onset. Twelve of the 13 cases fulfilled HLH-2004 criteria. The diagnosis of Histoplasma capsulatum infection was established by histological examination (13 of 13), culture (4 of 13), molecular method (2 of 13), and antigen or serological assays (2 of 13). Amphotericin B, posaconazole, and itraconazole show favorable activity against the fungus, seven patients used specific treatment for HLH. For analysis of outcomes, two of the 13 patients died. Our present case report and literature review show that disseminated Histoplasma capsulatum infection with HLH in the immunocompetent population becomes increasingly common in emerging endemic areas and have high mortality. It is necessary for clinicians to improve the awareness of disease diagnosis due to the atypical population and disease presentation. Timely diagnosis and early use of antifungal agents will lead to favorable prognosis.

Capsule endoscopy with retention of 4 years: A case report.

INTRODUCTION AND IMPORTANCE: Capsule endoscopy has been widely used in the diagnosis of small bowel diseases. Most CE can be smoothly excreted through the digestive tract. However, very few retention of CE may happen. CASE PRESENTATION: A 64-year-old man had been suffering from intermittent abdominal pain for 10 years. Capsule endoscopy was performed in local hospital 4 years ago. He was initially diagnosed with Crohn's disease and started on treatment. CTE and X-ray film of abdomen showed a suspected capsule endoscopy on the right side of pelvic cavity. Surgery was performed to remove the capsule. After the surgical treatment, no gastrointestinal symptoms relapsed for 9 months. CLINICAL DISCUSSION: It isn't uncommon for capsule endoscopy to be detained in Crohn's disease, because Strictures are the commonest complication of Crohn's disease. In order to prevent intestinal retention of capsule endoscopy, risk assessment should be carried out before capsule endoscopy. If detained CE isn't removed successfully by drug therapy and endoscopic therapy, surgery treatment has to be considered. CONCLUSION: In the present case, capsule endoscopy was found in the small intestine after 4 years, and the reason is worth pondering. We strongly recommend performing routine CTE, MRE and patency capsule examination before capsule endoscopy for patients suspected of stenosis. Routine abdominal X-ray film after examination is also useful for timely detection of capsule retention.

Prevalence, Risk Factors, and Prognostic Factors of Primary Malignant Bone Neoplasms with Bone Metastasis at Initial Diagnosis: A Population-Based Study.

Background: Bone metastasis (BM) has been proven to be responsible for the poor prognosis of primary malignant bone neoplasms (PMBNs). We aimed to identify the prevalence, risk factors, and prognostic factors for PMBNs patients with BM based on the Surveillance, Epidemiology, and End Results (SEER) database. Methods: 4,758 patients diagnosed with PMBNs from 2010 to 2018 were selected from the SEER database. All patients were divided into two groups: the BM group or the non-BM group. Pearson's chi-square test and Fisher's exact method were used to assess baseline characteristics, and logistic regression analysis was applied to assess risk factors. In addition, a nomogram was constructed based on the results of Cox regression analysis among 227 patients with BM. The good performance and clinical applicability of the nomogram were tested by the concordance index, operating characteristic curve, area under the curve, calibration curves, and decision curve analysis. Results: 227 (4.8%) patients had metastasis to bone at diagnosis. Primary site outside the extremities (axial: odds ratio, OR = 1.770; others: OR = 1.951), Ewing sarcoma (OR = 2.845), larger tumor size (5-8 cm: OR = 3.403; >8 cm: OR = 5.562), tumor extension beyond the periosteum (OR = 2.477), and regional lymph node metastasis (OR = 2.900) were associated with a higher risk of BM at the initial diagnosis of PMBNs. Five independent prognostic factors were found in the survival analysis: pathological type (chondrosarcoma vs. osteosarcoma: hazard ratio, HR = 0.342; Ewing sarcoma vs. osteosarcoma: HR = 0.592; and chordoma vs. osteosarcoma: HR = 0.015), marital status (HR = 2.457), pulmonary metastasis (HR = 1.934), surgery at the primary site (HR = 0.164), and chemotherapy (HR = 0.084). A nomogram based on these prognostic factors could be a good predictor of cancer-specific survival. Conclusions: We identified the prevalence, risk factors, and prognostic factors correlated with BM in PMBNs patients. The related nomogram could be a practical tool for therapeutic decision-making and individual counseling.

A novel LASSO-derived prognostic model predicting survival for non-small cell lung cancer patients with M1a diseases.

INTRODUCTION: The current American Joint Committee on Cancer (AJCC) M1a staging of non-small cell lung cancer (NSCLC) encompasses a wide disease spectrum, showing diverse prognosis. METHODS: Patients who diagnosed in an earlier period formed the training cohort, and those who diagnosed thereafter formed the validation cohort. Kaplan-Meier analysis was performed for the training cohort by dividing the M1a stage into three subgroups: (I) malignant pleural effusion (MPE) or malignant pericardial effusion (MPCE); (II) separate tumor nodules in contralateral lung (STCL); and (III) pleural tumor nodules on the ipsilateral lung (PTIL). Gender, age, histologic, N stage, grade, surgery for primary site, lymphadenectomy, M1a groups, and chemotherapy were selected as independent prognostic factors using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. And a nomogram was constructed using Cox hazard regression analysis. Accuracy and clinical practicability were separately tested by Harrell's concordance index, the receiver operating characteristic (ROC) curve, calibration plots, residual plot, the integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). RESULTS: The concordance index (0.661 for the training cohort and 0.688 for the validation cohort) and the area under the ROC curve (training cohort: 0.709 for 1-year and 0.727 for 2-year OS prediction; validation cohort: 0.737 for 1-year and 0.734 for 2-year OS prediction) indicated satisfactory discriminative ability of the nomogram. Calibration curve and DCA presented great prognostic accuracy, and clinical applicability. Its prognostic accuracy preceded the AJCC staging with evaluated NRI (1-year: 0.327; 2-year: 0.302) and IDI (1-year: 0.138; 2-year: 0.130). CONCLUSION: Our study established a nomogram for the prediction of 1- and 2-year OS in patients with NSCLC diagnosed with stage M1a, facilitating healthcare workers to accurately evaluate the individual survival of M1a NSCLC patients. The accuracy and clinical applicability of this nomogram were validated.

Bloodstream Infections Caused by Klebsiella pneumoniae Carbapenemase-Producing P. aeruginosa Sequence Type 463, Associated With High Mortality Rates in China: A Retrospective Cohort Study.

Objectives: Recently, KPC-producing P. aeruginosa has rapidly emerged and expanded in East China. Here we described the clinical impact and characteristics of bloodstream infections (BSIs) from the dominant KPC-producing CRPA belonging to Sequence Type (ST) 463. Methods: Retrospective cohort study was performed with CRPA BSI cases from 2019 to 2020 in a hospital in East China. Clinical characteristics, risk factors, and all-course mortality were evaluated. All CRPA isolates had whole-genome sequencing, antimicrobial susceptibility testing, and serum resistance assay. Representative isolates were tested for virulence in a Galleria mellonella infection model. Results: Among the 50 CRPA BSI cases, ST463 predominated (48.0%). In multivariate analysis, we found three independent risk factors for fatal outcome: KPC carriage (OR 4.8; CI95% 1.0-23.7; P = 0.05), Pitt bacteremia score (OR 1.3; CI95% 1.0-1.6; P = 0.02), and underlying hematological disease (OR 8.5; CI95% 1.6-46.4; P = 0.01). The baseline clinical variables were not statistically different across STs, however the 28-day mortality was significantly higher in ST463 cases than that in non-ST463 cases (66.7% vs 33.3%, P = 0.03). ExoU and exoS virulence genes coexisted in all ST463 isolates, and the carbapenem resistant gene blaKPC were produced in almost all ST463 isolates, significantly higher than in the non-ST463 group(95.8% vs 7.7%, P<0.001). ST463 CRPA isolates also showed higher resistance rates to antipseudomonal cephalosporins, monobactam, and fluoroquinolones. And ST463 CRPA was confirmed hypervirulence in the larvae model. The genome of one ST463 CRPA strain showed that the blaKPC-2 gene was the sole resistance gene located on a 41,104bp plasmid pZYPA01, carried on a 7-kb composite transposon-like element flanked by two IS26 elements (IS26-Tn3-tnpA-ISKpn27-blaKPC-2-ISKpn6-IS26). Plasmid from various species presented core blaKPC-2 was franked by mobile genetic element ISKpn27 and ISKpn6. Conclusions: In the ST463 CRPA BSI cohort, the mortality rates were higher than those in the non-ST463 CRPA BSI. The ST463 CRPA clone coharboring the blaKPC and exoU/exoS genes emerged and spread in East China, which might develop to a new threat in the clinic. Our results suggest that the surveillance of the new high-risk clone, ST463 CRPA, should be strengthened in China, even worldwide in the future.

Identification of chemosensory genes by antennal transcriptome analysis and expression profiles of odorant-binding proteins in parasitoid wasp Aulacocentrum confusum.

The endoparasitoid wasp, Aulacocentrum confusum (Hymenoptera: Braconidae), is a preponderant natural enemy of the larvae of Glyphodes pyloalis Walker (Lepidoptera: Pyralidae), which is a destructive pest of mulberry trees. We first constructed the antennal transcriptome database of A. confusum. In total, we obtained 48,262,304 clean reads from the dataset and assembled 24,324 unigenes. A total of 12,690 (52.17%) unigenes indicated significant similarity (E-value < 10-5) compared to known protein sequences of other species from the NCBI non-redundant protein database. Gene ontology (GO) and cluster of orthologous groups (COG) analyses were used to determine the functional categories of these genes. A total of 84 putative chemosensory genes were identified from the antennal transcriptome of A. confusum, including 11 putative odorant-binding protein (OBP) genes, six chemosensory protein (CSP) genes, 44 olfactory receptor (OR) genes (including one olfactory co-receptor, Orco), 19 ionotropic receptor (IR) genes, and four sensory neuron membrane protein (SNMP) genes. Results of qPCR assays indicated that among of 11 AconOBPs, nine AconOBP genes were significantly expressed in the antennae of A. confusum adults. AconOBP8 was significantly expressed in the abdomen and AconOBP10 was highly expressed in the thorax. These findings can build a basis for further study on the processes of chemosensory perception in A. confusum at the molecular level.

Comparative genomic analyses of IncpA1763-KPC plasmids.

Multi-replicon plasmids harboring the IncpA1763-KPC replicon together with other replicons are being increasingly reported among Enterobacteriaceae species. However, plasmids with single IncpA1763-KPC replicons are poorly studied as a different incompatibility (Inc) group, despite their rise in appearance in some strains. IncpA1763-KPC plasmids, pA1763-KPC, and p427113-2, from two clinical Klebsiella pneumoniae isolates were fully sequenced by high-throughput genome sequencing. Linear structural comparisons of IncpA1763-KPC backbone region were made between these two plasmids and six arbitrarily selected representative IncpA1763-KPC plasmids sequenced previously. A further detailed genomic comparison was carried out between plasmids pA1763-KPC, p427113-2, and pFB2.2, which show high homology across the backbone sequence to one another. Among all sequenced IncpA1763-KPC plasmids considered in this study, plasmids pA1763-KPC and p427113-2 showed the most complete IncpA1763-KPC backbones. These were composed of the IncpA1763-KPC replicon (repAIncpA1763-KPC and its iterons), the 5.6-kb IncpA1763-KPC -type maintenance region, the 27.7-kb IncFIIK -type maintenance region, and the 36.6-kb IncFIIK -type conjugal transfer regions. Compared with pA1763-KPC or p427113-2, the backbone regions of the other analyzed IncpA1763-KPC plasmids had gradually undergone different deletions or truncations, but shared small and core IncpA1763-KPC backbones including the IncpA1763-KPC replicon, IncpA1763-KPC -type maintenance region, and residual IncFIIK -type maintenance region. Accessory modules integrated into IncpA1763-KPC backbones included the multidrug-resistant module blaKPC-2 region in pA1763-KPC, the metal-resistance modules ars region together with ncr region in pFB2.2 and sil in pKPN-9a0d, the ISKpn14-to-IS26 region in p427113-2, and other non-resistance region in the respective plasmids. This detailed comparative genomics analysis of IncpA1763-KPC plasmids provides a deep insight into their diversification and evolution.

Secondary Bacterial Infections in Critical Ill Patients With Coronavirus Disease 2019.

Secondary bacterial infections occurred in 13.9% (5 of 36) of critical ill patients with coronavirus disease 2019. All 5 patients had been admitted to intensive care unit and received mechanical ventilation before developing bacterial infection. Active surveillance of culture should be performed for critically ill patients. Prevention of nosocomial infection should to be taken seriously.

Different screening frequencies of carbapenem-resistant Enterobacteriaceae in patients undergoing hematopoietic stem cell transplantation: which one is better?

BACKGROUND: A consensus has been reached that carbapenem-resistant Enterobacteriaceae (CRE) screening in immunosuppressed individuals can reduce the incidence of CRE bloodstream infection (BSI). METHODS: We retrospectively studied the clinical data of 395 consecutive HSCT patients from September 2017 to April 2019. From September 2017 to June 2018 (period 1), 200 patients received single CRE screening before transplantation. From July 2018 to April 2019 (period 2), 195 patients received continuous weekly CRE screening after admission. For patients colonized with CRE, targeted managements were received: (1) contact precautions and (2) preemptive CRE-targeted treatment if necessary. RESULTS: During period 1, 3 patients with CRE colonization were detected (1.5%). The CRE BSI rate was 2.0% (4 patients), and the related 30-day mortality was 50.0% (2 out of 4 patients). During period 2, 21 patients with CRE colonization were detected, and the detection rate was significantly higher than that in period 1 (P < 0.001). Of the 21 colonized patients, 4 (19.0%) patients were identified as positive for CRE at the first screening, 5 (23.8%) were identified at the second screening, and the remaining 12 (57.1%) were identified at the third or later screening. The CRE BSI rate decreased to 0.5% (1/195), and there were no CRE-related death. Fifteen colonized patients developed neutropenic fever. Thirteen colonizers were preemptively treated with tigecycline within 24 h of fever onset, and they achieved rapid temperature control. One colonizer received tigecycline later than 48 h after fever onset and ultimately survived due to the addition of polymyxin. The other received tigecycline later than 72 h after fever onset and died of septic shock. CONCLUSION: The increase in screening frequency contributed to the detection of patients with CRE colonization. Targeted managements for these colonized patients may contribute to reducing the incidence and mortality of CRE BSI, therefore improving the prognosis of patients.

Asymmetric Synthesis and Application of Chiral Spirosilabiindanes.

Reported here is the development of a class of chiral spirosilabiindane scaffolds by Rh-catalyzed asymmetric double hydrosilation, for the first time. Enantiopure SPSiOL (spirosilabiindane diol), a new type of chiral building block for the preparation of various chiral ligands and catalysts, was readily prepared on greater than 10 gram scale using this protocol. The potential of this new spirosilabiindane scaffold in asymmetric catalysis was preliminarily demonstrated by development of the corresponding monodentate phosphoramidite ligands (SPSiPhos), which were used in both a Rh-catalyzed hydrogenation and a Pd-catalyzed intramolecular carboamination.

Endogenous endophthalmitis caused by a multidrug-resistant hypervirulent Klebsiella pneumoniae strain belonging to a novel single locus variant of ST23: first case report in China.

BACKGROUND: Endogenous endophthalmitis caused by hypervirulent Klebsiella pneumoniae (HVKP) is an emerging infectious disease commonly with a devastating visual outcome. Most HVKP strains display a wild-type susceptibility profile to antibiotics. However, reports of antimicrobial-resistant HVKP have increased over time, which poses a serious therapeutic dilemma. CASE PRESENTATION: A 25-year-old man with a liver abscess and poorly controlled diabetes mellitus was admitted for endophthalmitis due to K. pneumoniae. The isolate displayed hypermucoviscosity as determined by a positive string test and exhibited resistance to ceftazidime, piperacillin-tazobactam and amikacin. Whole genome sequencing (WGS) analysis demonstrated the isolate to be a K1-serotype strain and belong to a novel single locus variant of ST23, ST2922. In addition to the virulence genes linked to HVKP, rmpA, magA, iucABCDiutA (aerobactin), ybtAPSTUX (yersiniabactin) and iroBDN (salmochelin), it was found to harbor extended-spectrum ß-lactamase (ESBL) gene (blaCTX-M-14), AmpC ß-lactamase gene (blaDHA), and 16S rRNA methylase gene (armA). CONCLUSIONS: This is the first known case of endogenous endophthalmitis caused by a multidrug-resistant HVKP strain ever reported in China. Early diagnosis and treatment with intravenous and intravitreal injection of carbapenem were essential for a favorable visual outcome.