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1.
Curr Zool ; 70(2): 174-181, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38726244

ABSTRACT

Theory predicts that males and females of dioecious species typically engage in an evolutionary sexual conflict over the frequency and choice of mating partner. Female sexual cannibalism, a particularly dramatic illustration of this conflict, is widespread in certain animal taxa including spiders. Nevertheless, females of some funnel weaving spiders that are generally aggressive to conspecifics enter a cataleptic state after male courtship, ensuring the males can mate without risk of attack. In this study, we demonstrated that the physical posture and duration, metabolites, and central neurotransmitters of females of Aterigena aculeata in sexual catalepsy closely resemble females in thanatosis but are distinct from those in anesthesia, indicating that the courted females feign death to eliminate the risk of potentially aggressive responses and thereby allow preferred males to mate. Unlike the taxonomically widespread thanatosis, which generally represents a deceptive visual signal that acts against the interest of the receivers, sexual catalepsy of females in the funnel weaving spiders may deliver a sexual-receptive signal to the courting males and thereby benefit both the signal senders and receivers. Therefore, sexual catalepsy in A. aculeata may not reflect a conflict but rather a confluence of interest between the sexes.

2.
Virulence ; 15(1): 2349768, 2024 12.
Article in English | MEDLINE | ID: mdl-38736039

ABSTRACT

ST11 is the most common lineage among carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in Asia. Diverse morphotypes resulting from genetic mutations are associated with significant differences in microbial characteristics among K. pneumoniae isolates. Here, we investigated the genetic determinants and critical characteristics associated with distinct morphotypes of ST11 CRKP. An ST11-KL47 CRKP isolate carrying a pLVPK-like virulence plasmid was isolated from a patient with a bloodstream infection; the isolate had the "mcsw" morphotype. Two distinct morphotypes ("ntrd" and "msdw") were derived from this strain during in vitro passage. Whole genome sequencing was used to identify mutations that cause the distinct morphotypes of ST11 CRKP. Transmission electron microscopy, antimicrobial susceptibility tests, growth assays, biofilm formation, virulence assays, membrane permeability assays, and RNA-seq analysis were used to investigate the specific characteristics associated with different morphotypes of ST11 CRKP. Compared with the parental mcsw morphotype, the ntrd morphotype resulted from mutation of genes involved in capsular polysaccharide biosynthesis (wza, wzc, and wbaP), a result validated by gene knockout experiments. This morphotype showed capsule deficiency and lower virulence potential, but higher biofilm production. By contrast, the msdw morphotype displayed competition deficiency and increased susceptibility to chlorhexidine and polymyxin B. Further analyses indicated that these characteristics were caused by interruption of the sigma factor gene rpoN by insertion mutations and deletion of the rpoN gene, which attenuated membrane integrity presumably by downregulating the phage shock protein operon. These data expand current understanding of genetic, virulence, and antimicrobial resistance characteristics associated with distinct morphotypes in ST11 CRKP.


Subject(s)
Anti-Bacterial Agents , Biofilms , Carbapenems , Klebsiella Infections , Klebsiella pneumoniae , Microbial Sensitivity Tests , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/pathogenicity , Virulence , Klebsiella Infections/microbiology , Humans , Anti-Bacterial Agents/pharmacology , Biofilms/growth & development , Carbapenems/pharmacology , Animals , Carbapenem-Resistant Enterobacteriaceae/genetics , Carbapenem-Resistant Enterobacteriaceae/drug effects , Mice , Mutation , Whole Genome Sequencing , Plasmids/genetics , Drug Resistance, Bacterial
3.
Int J Antimicrob Agents ; 63(6): 107176, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38642811

ABSTRACT

OBJECTIVES: Optimising blood culture processing is important to ensure that bloodstream infections are accurately diagnosed while minimising adverse events caused by antibiotic abuse. This study aimed to evaluate the impact of optimised blood culture processes on antibiotic use, clinical outcomes and economics in intensive care unit (ICU) patients with positive blood cultures. METHODS: From March 2020 to October 2021, this microbiology laboratory implemented a series of improvement measures, including the clinical utility of Fastidious Antimicrobial Neutralization (FAN® PLUS) bottles for the BacT/Alert Virtuo blood culture system, optimisation of bottle reception, graded reports and an upgraded laboratory information system. A total of 122 ICU patients were included in the pre-optimisation group from March 2019 to February 2020, while 179 ICU patients were included in the post-optimisation group from November 2021 to October 2022. RESULTS: Compared with the pre-optimisation group, the average reporting time of identification and antimicrobial sensitivity was reduced by 16.72 hours in the optimised group. The time from admission to targeted antibiotic therapy within 24 hours after receiving both the Gram stain report and the final report were both significantly less in the post-optimisation group compared with the pre-optimisation group. The average hospitalisation time was reduced by 6.49 days, the average antimicrobial drug cost lowered by $1720.85 and the average hospitalisation cost by $9514.17 in the post-optimisation group. CONCLUSIONS: Optimising blood culture processing was associated with a significantly increased positive detection rate, a remarkable reduction in the length of hospital stay and in hospital costs for ICU patients with bloodstream infections.

4.
Int J Antimicrob Agents ; 63(5): 107152, 2024 May.
Article in English | MEDLINE | ID: mdl-38513747

ABSTRACT

INTRODUCTION: Ceftazidime-avibactam (CAZ-AVI) is a new option to treat KPC- and OXA-48 carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. However, clinical evidence is limited regarding its use in treating CRKP infections, especially in solid organ transplantation (SOT) recipients. In this study, we assessed the efficacy of CAZ-AVI in treating CRKP infections in both the general population and the SOT recipients in comparison with other antibiotic regimens. METHODS: This is a single-centre retrospective cohort study of patients admitted between January 1, 2018 and June 30, 2021 with the diagnosis of CRKP infections receiving either CAZ-AVI or other regimens ≥ 72 hours and clinical outcomes were analysed. RESULTS: Of 200 patients with CRKP infections, 67 received CAZ-AVI, 133 received other regimens, and 50 were SOT recipients. In the SOT cohort, 30 patients received CAZ-AVI, and 20 received other regimens. The overall 30-day mortality was 38% in the SOT cohort. Compared with patients receiving other regimens, CAZ-AVI therapy resulted in lower 30-day mortality (23.3% vs. 60%, P = 0.014) and 90-day mortality (35.7% vs. 86.7%, P = 0.003), higher clinical cure (93.3% vs. 40%, P < 0.001) and microbiological clearance. Similar promising results of CAZ-AVI were also shown in the whole population cohort. Moreover, clinical outcomes of SOT recipients receiving CAZ-AVI were not inferior to those without SOT. CONCLUSIONS: CAZ-AVI therapy was associated with better clinical outcomes in CRKP infections in both the general population and SOT recipients. Considering the limitations of the present study, well-conducted RCTs are still warranted to confirm these findings.


Subject(s)
Anti-Bacterial Agents , Azabicyclo Compounds , Ceftazidime , Drug Combinations , Klebsiella Infections , Klebsiella pneumoniae , Organ Transplantation , Humans , Ceftazidime/therapeutic use , Azabicyclo Compounds/therapeutic use , Male , Female , Retrospective Studies , Middle Aged , Klebsiella pneumoniae/drug effects , Klebsiella Infections/drug therapy , Klebsiella Infections/mortality , Klebsiella Infections/microbiology , Anti-Bacterial Agents/therapeutic use , Aged , Organ Transplantation/adverse effects , Carbapenem-Resistant Enterobacteriaceae/drug effects , Transplant Recipients , Adult , Carbapenems/therapeutic use , Treatment Outcome , Microbial Sensitivity Tests
5.
Emerg Microbes Infect ; 13(1): 2317915, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38356197

ABSTRACT

The escalation of antibiotic resistance and the diminishing antimicrobial pipeline have emerged as significant threats to public health. The ESKAPE pathogens - Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. - were initially identified as critical multidrug-resistant bacteria, demanding urgently effective therapies. Despite the introduction of various new antibiotics and antibiotic adjuvants, such as innovative ß-lactamase inhibitors, these organisms continue to pose substantial therapeutic challenges. People's Republic of China, as a country facing a severe bacterial resistance situation, has undergone a series of changes and findings in recent years in terms of the prevalence, transmission characteristics and resistance mechanisms of antibiotic resistant bacteria. The increasing levels of population mobility have not only shaped the unique characteristics of antibiotic resistance prevalence and transmission within People's Republic of China but have also indirectly reflected global patterns of antibiotic-resistant dissemination. What's more, as a vast nation, People's Republic of China exhibits significant variations in the levels of antibiotic resistance and the prevalence characteristics of antibiotic resistant bacteria across different provinces and regions. In this review, we examine the current epidemiology and characteristics of this important group of bacterial pathogens, delving into relevant mechanisms of resistance to recently introduced antibiotics that impact their clinical utility in China.


Subject(s)
Bacterial Infections , Enterococcus faecium , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , Bacterial Infections/microbiology , Klebsiella pneumoniae , Drug Resistance, Multiple, Bacterial
6.
J Microbiol Immunol Infect ; 57(2): 300-308, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38350840

ABSTRACT

PURPOSES: This study determined the synergy of polymyxin B (POLB) and colistin (COL) with 16 other tested antimicrobial agents in the inhibition of multidrug-resistant Acinetobacter baumannii (MDR-AB). METHODS: We used chequerboard assays to determine synergy between the drugs against 50 clinical MDR-AB from a tertiary hospital in the Zhejiang province in 2019, classifying combinations as either antagonistic, independent, additive, or synergistic. The efficacy of hit combinations which showed highest synergistic rate were confirmed using time-kill assays. RESULTS: Both POLB and COL displayed similar bactericidal effects when used in combination with these 16 tested drugs. Antagonism was only observed for a few strains (2%) exposed to a combination of POLB and cefoperazone/sulbactam (CSL). A higher percentage of synergistic combinations with POLB and COL were observed with rifabutin (RFB; 90%/96%), rifampicin (RIF; 60%/78%) and rifapentine (RFP; 56%/76%). Time-kill assays also confirmed the synergistic effect of POLB and rifamycin class combinations. 1/2 MIC rifamycin exposure can achieve bacterial clearance when combined with 1/2 MIC POLB or COL. CONCLUSION: Nearly no antagonism was observed when combining polymyxins with other drugs by both chequerboard and time-kill assays, suggesting that polymyxins may be effective in combination therapy. The combinations of POLB/COL with RFB, RIF, and RFP displayed neat synergy, with RFB showing the greatest effect.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Humans , Colistin/pharmacology , Colistin/therapeutic use , Polymyxin B/pharmacology , Drug Synergism , Acinetobacter Infections/drug therapy , Acinetobacter Infections/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Microbial Sensitivity Tests , Drug Resistance, Multiple, Bacterial
7.
Zookeys ; 1190: 195-212, 2024.
Article in English | MEDLINE | ID: mdl-38323097

ABSTRACT

Taxonomic notes on the Talaus species from China are provided. Two new species, T.yuyang Yao & Liu, sp. nov. and T.zhangjiangkou Yao & Liu, sp. nov. are described and illustrated, and a further three species are redescribed based on their genitalic characters: T.dulongjiang Tang, Yin, Ubick & Peng, 2008, T.niger Tang, Yin, Ubick & Peng, 2008, and T.sulcus Tang & Li, 2010. The species T.xiphosus Zhu & Ono, 2007 is considered a junior synonym of T.triangulifer Simon, 1886 based on an examination of many recently collected female and male specimens from Guangxi Province, China. Diagnoses, detailed illustrations and a map of distributional records of the six treated species of Talaus in China are provided.

8.
Antibiotics (Basel) ; 13(2)2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38391551

ABSTRACT

Bloodstream infections by bacteria, especially multidrug-resistant bacteria, remain a worldwide public health concern. We evaluated the antibacterial activity of ceftobiprole and comparable drugs against different bloodstream isolates and different sequence types of methicillin-resistant Staphylococcus aureus (MRSA) in China. We found that MRSA, methicillin-susceptible Staphylococcus aureus (MSSA), and methicillin-susceptible coagulase-negative Staphylococcus (MSCNS) displayed ceftobiprole sensitivity rates of >95%, which are similar to the rates for linezolid, daptomycin, and vancomycin. Of the tested MRCNS strains, 90.4% were sensitive to ceftobiprole. The sensitivities of ST59, ST398, and ST22 MRSA to ceftobiprole were higher than that of ST239. Ceftobiprole's MIC50/90 value against Enterococcus faecalis was 0.25/2 mg/L, whereas Enterococcus faecium was completely resistant to this drug. Ceftobiprole exhibited no activity against ESBL-positive Enterobacterales, with resistance rates between 78.6% and 100%. For ESBL-negative Enterobacterales, excluding Klebsiella oxytoca, the sensitivity to ceftobiprole was comparable to that of ceftazidime, ceftriaxone, and cefepime. The MIC50/90 value of ceftobiprole against Pseudomonas aeruginosa was 2/16 mg/L, and for Acinetobacter baumannii, it was 32/>32 mg/L. Thus, ceftobiprole shows excellent antimicrobial activity against ESBL-negative Enterobacterales and Pseudomonas aeruginosa (comparable to that of ceftazidime, ceftriaxone, and cefepime); however, it is not effective against ESBL-positive Enterobacterales and Acinetobacter baumannii. These results provide important information to clinicians.

9.
Emerg Microbes Infect ; 13(1): 2316809, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38323591

ABSTRACT

Previous studies have mainly focused on outpatient cases of skin and soft tissue infections (SSTIs), with limited attention to inpatient occurrences. Thus, we aimed to compare the clinical parameters of inpatients with SSTIs, performed genomic characterization, and determined the subtypes of Panton-Valentine leucocidin (PVL) bacteriophages of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from these patients. We found that PVL-positive patients had shorter hospital stays (mean, 9 vs. 24 days; p < 0.001) and abscess resolution durations (mean, 8 vs. 13 days; p < 0.01). PVL-positive MRSA-induced SSTIs were more frequently associated with abscesses [36/55 (65.5%) vs. 15/124 (12.1%), p < 0.001], with 52.7% undergoing incision and drainage; over 80% of PVL-negative patients received incision, drainage, and antibiotics. In PVL-positive patients receiving empirical antibiotics, anti-staphylococcal agents such as vancomycin and linezolid were administered less frequently (32.7%, 18/55) than in PVL-negative patients (74.2%, 92/124), indicating that patients with PVL-positive SSTIs are more likely to require surgical drainage rather than antimicrobial treatment. We also found that the ST59 lineage was predominant, regardless of PVL status (41.3%, 74/179). Additionally, we investigated the linear structure of the lukSF-PV gene, revealing that major clusters were associated with specific STs, suggesting independent acquisition of PVL by different strain types and indicating that significant diversity was observed even within PVL-positive strains detected in the same facility. Overall, our study provides comprehensive insights into the clinical, genetic, and phage-related aspects of MRSA-induced SSTIs in hospitalized patients and contributes to a more profound understanding of the epidemiology and evolution of these pathogens in the Chinese population.


Subject(s)
Community-Acquired Infections , Methicillin-Resistant Staphylococcus aureus , Soft Tissue Infections , Staphylococcal Infections , Staphylococcal Skin Infections , Humans , Inpatients , Soft Tissue Infections/epidemiology , Retrospective Studies , Leukocidins/genetics , Staphylococcal Infections/epidemiology , Staphylococcal Skin Infections/epidemiology , Exotoxins/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Abscess , Community-Acquired Infections/epidemiology
10.
Zookeys ; 1189: 287-325, 2024.
Article in English | MEDLINE | ID: mdl-38314111

ABSTRACT

Eleven leptonetid species belonging to four genera collected in Jiangxi and Fujian Provinces, China are presented. Ten new species of midget cave spiders from southern China are diagnosed, described, and illustrated: Leptoneteladawu Yao & Liu, sp. nov., L.yuanhaoi Yao & Liu, sp. nov. and L.zuojiashanensis Yao & Liu, sp. nov. from Jiangxi; Longileptonetaguadunensis Yao & Liu, sp. nov., L.huboliao Yao & Liu, sp. nov., L.jiaxiani Yao & Liu, sp. nov., L.letuensis Yao & Liu, sp. nov., L.renzhouensis Yao & Liu, sp. nov., L.tianmenensis Yao & Liu, sp. nov., and Pararanamingxuani Yao & Liu, sp. nov. from Fujian. Furthermore, Falcileptonetamonodactyla (Yin, Wang & Wang, 1984) is recorded from Jiangxi province for the first time. Distributions records are given for all investigated species.

11.
Clin Microbiol Infect ; 30(4): 507-514, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38295990

ABSTRACT

OBJECTIVES: To study the clinical relevance, mechanisms, and evolution of polymyxin B (POLB) heteroresistance (PHR) in carbapenem-resistant Klebsiella pneumoniae (CRKP), potentially leading to a significant rise in POLB full resistant (FR) CRKP. METHODS: Total of 544 CRKP isolates from 154 patients treated with POLB were categorized into PHR and POLB non-heteroresistance (NHR) groups. We performed statistical analysis to compare clinical implications and treatment responses. We employed whole-genome sequencing, bioinformatics, and PCR to study the molecular epidemiology, mechanisms behind PHR, and its evolution into FR. RESULTS: We observed a considerable proportion (118 of 154, 76.62%) of clinically undetected PHR strains before POLB exposure, with a significant subset of them (33 of 118, 27.97%) evolving into FR after POLB treatment. We investigated the clinical implications, epidemiological characteristics, mechanisms, and evolutionary patterns of PHR strains in the context of POLB treatment. About 92.86% (39 of 42) of patients had PHR isolates before FR, highlighting the clinical importance of PHR. the ST15 exhibited a notably lower PHR rate (1 of 8, 12.5% vs. 117 of 144, 81.25%; p < 0.01). The ST11 PHR strains showing significantly higher rate of mgrB mutations by endogenous insertion sequences in their resistant subpopulation (RS) compared with other STs (78 of 106, 73.58% vs. 4 of 12, 33.33%; p < 0.01). The mgrB insertional inactivation rate was lower in FR isolates than in the RS of PHR isolates (15 of 42, 35.71% vs. 84 of 112, 75%; p < 0.01), whereas the pmrAB mutation rate was higher in FR isolates than in the RS of PHR isolates (8 of 42, 19.05% vs. 2 of 112, 1.79%; p < 0.01). The evolution from PHR to FR was influenced by subpopulation dynamics and genetic adaptability because of hypermutability. DISCUSSION: We highlight significant genetic changes as the primary driver of PHR to FR in CRKP, underscoring polymyxin complexity.


Subject(s)
Carbapenem-Resistant Enterobacteriaceae , Klebsiella Infections , Humans , Polymyxins , Polymyxin B/pharmacology , Clinical Relevance , Klebsiella pneumoniae/genetics , Retrospective Studies , Genomics , Carbapenem-Resistant Enterobacteriaceae/genetics , Carbapenems/pharmacology , Klebsiella Infections/drug therapy , Klebsiella Infections/epidemiology , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests
12.
Org Lett ; 26(3): 591-596, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38214498

ABSTRACT

In the presence of a thiyl radical species, the catalytic Markovnikov thiol-ene reaction is challenging because it prefers to proceed via a radical pathway, thereby leading to anti-Markovnikov selectivity. In this work, a rare example of thiyl radical engaged in Markovnikov thiol-ene reaction enabled by cobalt catalysis is reported. This protocol features the avoidance of unique oxidants, exclusive regioselectivity, and broad substrate scope. Scalable synthesis and late-stage modification of complex molecules demonstrate the practicability of the protocol.

13.
Sci Rep ; 14(1): 2199, 2024 01 25.
Article in English | MEDLINE | ID: mdl-38273053

ABSTRACT

Leprosy and psoriasis rarely coexist, the specific molecular mechanisms underlying their mutual exclusion have not been extensively investigated. This study aimed to reveal the underlying mechanism responsible for the mutual exclusion between psoriasis and leprosy. We obtained leprosy and psoriasis data from ArrayExpress and GEO database. Differential expression analysis was conducted separately on the leprosy and psoriasis using DEseq2. Differentially expressed genes (DEGs) with opposite expression patterns in psoriasis and leprosy were identified, which could potentially involve in their mutual exclusion. Enrichment analysis was performed on these candidate mutually exclusive genes, and a protein-protein interaction (PPI) network was constructed to identify hub genes. The expression of these hub genes was further validated in an external dataset to obtain the critical mutually exclusive genes. Additionally, immune cell infiltration in psoriasis and leprosy was analyzed using single-sample gene set enrichment analysis (ssGSEA), and the correlation between critical mutually exclusive genes and immune cells was also examined. Finally, the expression pattern of critical mutually exclusive genes was evaluated in a single-cell transcriptome dataset. We identified 1098 DEGs in the leprosy dataset and 3839 DEGs in the psoriasis dataset. 48 candidate mutually exclusive genes were identified by taking the intersection. Enrichment analysis revealed that these genes were involved in cholesterol metabolism pathways. Through PPI network analysis, we identified APOE, CYP27A1, FADS1, and SOAT1 as hub genes. APOE, CYP27A1, and SOAT1 were subsequently validated as critical mutually exclusive genes on both internal and external datasets. Analysis of immune cell infiltration indicated higher abundance of 16 immune cell types in psoriasis and leprosy compared to normal controls. The abundance of 6 immune cell types in psoriasis and leprosy positively correlated with the expression levels of APOE and CYP27A1. Single-cell data analysis demonstrated that critical mutually exclusive genes were predominantly expressed in Schwann cells and fibroblasts. This study identified APOE, CYP27A1, and SOAT1 as critical mutually exclusive genes. Cholesterol metabolism pathway illustrated the possible mechanism of the inverse association of psoriasis and leprosy. The findings of this study provide a basis for identifying mechanisms and therapeutic targets for psoriasis.


Subject(s)
Arthrogryposis , Leprosy , Psoriasis , Humans , Leprosy/genetics , Psoriasis/genetics , Cholesterol , Apolipoproteins E , Computational Biology
14.
BMC Genomics ; 25(1): 2, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38166565

ABSTRACT

BACKGROUND: The infection of carbapenem-resistant organisms was a huge threat to human health due to their global spread. Dealing with a carbapenem-resistant Serratia marcescens (CRSM) infection poses a significant challenge in clinical settings. This study aims to provide insights into strategies for controlling CRSM infection by exploring the transformation mechanism of carbapenem-resistance. METHODS: We used whole genome sequencing (WGS) to investigate the mechanism of carbapenem resistance in 14 S. marcescens isolates in vivo. The expression level of related genes and the minimum inhibitory concentration of meropenem (MICMEM) were also evaluated to confirm the mechanism of carbapenem resistance. RESULTS: Seven groups of S. marcescens, each consisting of two strains, were collected from a hospital and displayed a shift in MICMEM from low to high levels. Homology analysis revealed that the isolates in five groups were significantly different from the remaining two. WGS and experimental evidence indicated that four groups of strains developed carbapenem resistance by acquiring the blaKPC (obtaining group), while two groups (persisting group) increased the expression level of the blaKPC. In contrast, isolates in the last group (missing group) did not carry the blaKPC. All strains possessed multiple ß-lactamase genes, including blaCTX-M-14, blaSRT-1, and blaSRT-2. However, only in the missing group, the carbapenem-resistant strain lost an outer membrane protein-encoding gene, leading to increased blaCTX-M-14 expression compared to the carbapenem-susceptible strain. CONCLUSION: The study findings suggest that S. marcescens strains developed diverse carbapenem resistance in vivo through the evolution of drug resistance, rather than through clone replacement. We hypothesize that carbapenem resistance in S. marcescens was due to certain clonal types with a distinct mechanism.


Subject(s)
Carbapenems , Serratia marcescens , Humans , Carbapenems/pharmacology , Meropenem/pharmacology , beta-Lactamases/genetics , beta-Lactamases/metabolism , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology
15.
Gynecol Oncol ; 180: 35-43, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38041901

ABSTRACT

OBJECTIVE: To define molecular features of ovarian cancer (OC) with germline pathogenic variants (PVs) in non-BRCA homologous recombination (HR) genes and analyze survival compared to BRCA1/2 and wildtype (WT) OC. METHODS: We included patients with OC undergoing tumor-normal sequencing (MSK-IMPACT) from 07/01/2015-12/31/2020, including germline assessment of BRCA1/2 and other HR genes ATM, BARD1, BRIP1, FANCA, FANCC, NBN, PALB2, RAD50, RAD51B, RAD51C, and RAD51D. Biallelic inactivation was assessed within tumors. Progression-free (PFS) and overall survival (OS) were calculated from pathologic diagnosis using the Kaplan-Meier method with left truncation. Whole-exome sequencing (WES) was performed in a subset. RESULTS: Of 882 patients with OC, 56 (6.3%) had germline PVs in non-BRCA HR genes; 95 (11%) had BRCA1-associated OC (58 germline, 37 somatic); and 59 (6.7%) had BRCA2-associated OC (40 germline, 19 somatic). High rates of biallelic alterations were observed among germline PVs in BRIP1 (11/13), PALB2 (3/4), RAD51B (3/4), RAD51C (3/4), and RAD51D (8/10). In cases with WES (27/35), there was higher tumor mutational burden (TMB; median 2.5 [1.1-6.0] vs. 1.2 mut/Mb [0.6-2.6]) and enrichment of HR-deficient (HRD) mutational signatures in tumors associated with germline PALB2 and RAD51B/C/D compared with BRIP1 PVs (p < 0.01). Other features of HRD, including telomeric-allelic imbalance (TAI) and large-scale state transitions (LSTs), were similar. Although there was heterogeneity in PFS/OS by gene group, only BRCA1/2-associated OC had improved survival compared to WT OC (p < 0.01). CONCLUSIONS: OCs associated with germline PVs in non-BRCA HR genes represent a heterogenous group, with PALB2 and RAD51B/C/D associated with an HRD phenotype.


Subject(s)
BRCA1 Protein , Ovarian Neoplasms , Humans , Female , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Ovarian Neoplasms/pathology , Germ-Line Mutation , Homologous Recombination , Phenotype , Germ Cells/pathology , Genetic Predisposition to Disease
16.
Ann Clin Microbiol Antimicrob ; 22(1): 107, 2023 Dec 10.
Article in English | MEDLINE | ID: mdl-38072972

ABSTRACT

OBJECTIVE: To evaluate effect of inoculum size of extended-spectrum ß-Lactamase (ESBL)-producing-, AmpC-producing-, and KPC-producing Escherichia coli and Klebsiella pneumoniae on the in vitro antibacterial effects of imipenem/relebactam (IMR) and ceftazidime/avibactam (CZA). METHODS: We compared the impact of inoculum size on IMR and CZA of sixteen clinical isolates and three standard isolates through antimicrobial susceptibility tests, time-kill assays and in vitro PK/PD studies. RESULTS: When inoculum size increased from 105 to 107 CFU/mL, an inoculum effect was observed for 26.3% (5/19) and 52.6% (10/19) of IMR and CZA, respectively; time-kill assays revealed that the concentration of CZA increased from ≥ 4 × MIC to 16 × MIC to reach 99.9% killing rate against K. pneumoniae ATCC-BAA 1705 (KPC-2-, OXA-9- and SHV-182-producing) and 60,700 (SHV-27- and DHA-1-producing). While for IMR, a concentration from 1 × MIC to 4 × MIC killed 99.9% of the four strains. When the inoculum size increased to 109 CFU/mL, neither IMR nor CZA showed a detectable antibacterial effect, even at a high concentration. An in vitro PK/PD study revealed a clear bactericidal effect when IMR administered as 1.25 g q6h when inoculum size increased. CONCLUSION: An inoculum effect on CZA was observed more frequent than that on IMR. Among the ß-lactamase-producing strains, the inoculum effect was most common for SHV-producing and KPC-producing strains.


Subject(s)
Ceftazidime , Klebsiella pneumoniae , Humans , Ceftazidime/pharmacology , Escherichia coli , Bacterial Proteins/genetics , Anti-Bacterial Agents/pharmacology , beta-Lactamases/genetics , Drug Combinations , Imipenem/pharmacology , Microbial Sensitivity Tests
17.
Antimicrob Resist Infect Control ; 12(1): 127, 2023 11 16.
Article in English | MEDLINE | ID: mdl-37974231

ABSTRACT

Antimicrobial resistance (AMR) is a serious, worldwide public health crisis. Surveillance of antimicrobial use forms part of an essential strategy to contain AMR. We aimed to conduct a national point prevalence survey (PPS) on antimicrobial use, and to compare this data with similar international surveillance programs to provide a reference for future AMR strategy development in China. Twenty general hospitals encompassing 10,881 beds and 10,209 inpatients around the country participated the survey using a standardized protocol, at 8am of someday from October 10th to November 31st, 2019. Of the patients, 37.00% (3777/10209) received antimicrobial agents, 31.30% (1630/5208) had surgical operations, and 76.63% (1249/1630) received prophylactic antibiotic. The prevalence of antimicrobial use in medical, surgical, and intensive care units (ICU) patients was 38.84% (1712/4408), 32.07% (1670/5208), and 66.61% (395/593), respectively. Of prescriptions, 5.79% (356/6151) were made in the absence of indication. The intensity of antimicrobial use was 61.25 DDDs/100 patient days, while the intensity of use in internal medicine, surgery, and ICU were 67.79, 45.81, 124.45 DDDs/100 patient days, respectively. Only 11.62% (715/6151) of prescriptions had a reason described in the patient record. Furthermore, 8.44% (210/2487), 14.19% (424/2989), and 12% (81/675) of the prescriptions in internal medicine, surgery, and ICU had a recorded indication, respectively. The review and stop date recorded for antimicrobial therapy was 43.73% (1976/4518). Of the patients, 38.07% (1438/3777) received combination therapy. The classes of antimicrobials prescribed were limited, and the proportion of prescriptions encompassed by the top 20 antimicrobial agents was 75.06% (4617/6151). The prevalence of antimicrobial use in China is close to that of Sweden, the UK, and Canada, but lower than that in India, and higher than that in Switzerland. The data described in this report indicate that the quality of antimicrobial prescriptions requires improvement in China. Further, hospitals should implement professional interventions to improve the rational use of antimicrobials.


Subject(s)
Anti-Infective Agents , Hospitals, General , Anti-Infective Agents/therapeutic use , Surveys and Questionnaires , China
18.
Microbiol Spectr ; 11(6): e0160223, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-37815354

ABSTRACT

IMPORTANCE: Elizabethkingia meningoseptica is an emerging infectious agent associated with life-threatening infections in immunocompromised individuals. However, there are limited data available on the genomic features of E. meningoseptica. This study aims to characterize the geographical distribution, phylogenetic evolution, pathogenesis, and transmission of this bacterium. A systematic analysis of the E. meningoseptica genome revealed that a common ancestor of this bacterium existed 90 years ago. The evolutionary history showed no significant relationship with the sample source, origin, or region, despite the presence of genetic diversity. Whole genome sequencing data also demonstrated that E. meningoseptica bacteria possess inherent resistance and pathogenicity, enabling them to spread within the same hospital and even across borders. This study highlights the potential for E. meningoseptica to cause severe nosocomial outbreaks and horizontal transmission between countries worldwide. The available evidence is crucial for the development of evidence-based public health policies to prevent global outbreaks caused by emerging pathogens.


Subject(s)
Chryseobacterium , Flavobacteriaceae Infections , Humans , Flavobacteriaceae Infections/epidemiology , Flavobacteriaceae Infections/microbiology , Phylogeny , Genomics , Disease Outbreaks , Probability , Anti-Bacterial Agents/therapeutic use
19.
Front Immunol ; 14: 1244534, 2023.
Article in English | MEDLINE | ID: mdl-37781359

ABSTRACT

Background: Posttransplant lymphoproliferative disorders (PTLDs) are uncommon but serious complications in patients following solid organ transplantation. Primary Epstein-Barr virus (EBV) infection is a risk factor for the development of PTLD, especially early-onset PTLD, in EBV-negative recipients. To date, however, there are no specific guidelines on the threshold of EBV-DNA load for therapeutic intervention, the source for measurement (e.g., blood, bronchoalveolar fluid), or the use of antiviral agents as prophylaxis for early PTLD prevention in EBV-mismatched patients. Methods: The present study describes a 56-year-old male lung transplant recipient diagnosed with EBV-associated PTLD. Results: This patient had a history of invasive fungal disease and Mucor and Aspergillus fumigatus infections in the early post-transplant period, necessitating antifungal therapy throughout the course of the disease. The patient was EBV-positive 15 days after transplantation, with lung CT showing multiple bilateral nodules of varying sizes beginning 98 days after transplantation. A lung biopsy showed PTLD, and next-generation sequencing (NGS) revealed EBV. This patient, however, did not receive any antiviral therapy for early PTLD prevention or any PTLD-related treatment. He died 204 days after lung transplantation. Conclusion: The present study describes a lung transplant recipient who developed EBV-associated PTLD, a non-negligible disease, after solid organ transplantation. Monitoring EBV-DNA load is important, as a sudden increase may be a sensitive indicator of PTLD. An earlier diagnosis may increase the likelihood of successful treatment.


Subject(s)
Epstein-Barr Virus Infections , Lung Transplantation , Lymphoproliferative Disorders , Male , Humans , Middle Aged , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/drug therapy , Herpesvirus 4, Human/genetics , Transplant Recipients , Lung Transplantation/adverse effects , Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/drug therapy , Lymphoproliferative Disorders/etiology , Lung/diagnostic imaging , DNA/therapeutic use
20.
Insects ; 14(10)2023 Sep 25.
Article in English | MEDLINE | ID: mdl-37887793

ABSTRACT

Beet webworms, Loxostege sticticalis L. (Lepidoptera: Pyralidae), are one of the most destructive pest insects in northern China, and their populations outbreak periodically. Developing an indicator that defines the ending and beginning of the occurrence period cycle is urgent for the population forecast and theoretical study. The sex ratio can be a primary pathway through which species regulate population size. We measured the maximum mating potential of both females and males and the population net reproductive rate under different sex ratios (e.g., 3:1, 2:1, 1:1, 1:2, 1:3). The maximum mating frequency of males was 2.91 times that of females. The progeny contribution per mating decreased with increased mating times in males. The variation in population net reproductive rate affected by the sex ratio fits the parabolic curve analysis and peaked at 1.82 for females vs. males. Our results illustrate the quantitative connection phenomenon shown by the historical data: population outbreaks occur at a sex ratio of two or more and collapse at a sex rate lower than one. Simultaneously, the sex ratio may be utilized as a definite indicator for the beginning and end of the future occurrence cycle in the beet webworm.

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