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Emerging Infectious Diseases Nov 2023In February 2022, a critically ill patient colonized with a carbapenem-resistant K. pneumoniae producing KPC-3 and VIM-1 carbapenemases was hospitalized for SARS-CoV-2...
In February 2022, a critically ill patient colonized with a carbapenem-resistant K. pneumoniae producing KPC-3 and VIM-1 carbapenemases was hospitalized for SARS-CoV-2 in the intensive care unit of Policlinico Umberto I hospital in Rome, Italy. During 95 days of hospitalization, ceftazidime/avibactam, meropenem/vaborbactam, and cefiderocol were administered consecutively to treat 3 respiratory tract infections sustained by different bacterial agents. Those therapies altered the resistome of K. pneumoniae sequence type 512 colonizing or infecting the patient during the hospitalization period. In vivo evolution of the K. pneumoniae sequence type 512 resistome occurred through plasmid loss, outer membrane porin alteration, and a nonsense mutation in the cirA siderophore gene, resulting in high levels of cefiderocol resistance. Cross-selection can occur between K. pneumoniae and treatments prescribed for other infective agents. K. pneumoniae can stably colonize a patient, and antimicrobial-selective pressure can promote progressive K. pneumoniae resistome evolution, indicating a substantial public health threat.
Topics: Humans; Ceftazidime; Meropenem; Anti-Bacterial Agents; Klebsiella pneumoniae; Bacterial Proteins; beta-Lactamases; Italy; Klebsiella Infections; Microbial Sensitivity Tests; Cefiderocol
PubMed: 37877547
DOI: 10.3201/eid2911.230921 -
IScience Jul 2023The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) Omicron variant sub-lineages spread rapidly worldwide, mostly due to their immune-evasive properties....
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) Omicron variant sub-lineages spread rapidly worldwide, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for effective anti-SARS-CoV-2 agents against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production, and potential for delivery via inhalation. Here, we characterize the receptor binding domain (RBD)-specific nanobody W25 and show superior neutralization activity toward Omicron sub-lineages in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. evaluation of W25 prophylactic and therapeutic treatments across multiple SARS-CoV-2 variant infection models, together with W25 biodistribution analysis in mice, demonstrates favorable pre-clinical properties. Together, these data endorse W25 for further clinical development.
PubMed: 37361875
DOI: 10.1016/j.isci.2023.107085 -
Journal of Clinical Oncology : Official... Jun 2024JCO We report 3-year efficacy and safety results from the phase III CheckMate 649 trial. Patients with previously untreated advanced or metastatic gastroesophageal... (Randomized Controlled Trial)
Randomized Controlled Trial
First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial.
JCO We report 3-year efficacy and safety results from the phase III CheckMate 649 trial. Patients with previously untreated advanced or metastatic gastroesophageal adenocarcinoma were randomly assigned to nivolumab plus chemotherapy or chemotherapy. Primary end points were overall survival (OS) and progression-free survival (PFS) by blinded independent central review (BICR) in patients whose tumors expressed PD-L1 combined positive score (CPS) ≥5. With 36.2-month minimum follow-up, for patients with PD-L1 CPS ≥5, the OS hazard ratio (HR) for nivolumab plus chemotherapy versus chemotherapy was 0.70 (95% CI, 0.61 to 0.81); 21% versus 10% of patients were alive at 36 months, respectively; the PFS HR was 0.70 (95% CI, 0.60 to 0.81); 36-month PFS rates were 13% versus 8%, respectively. The objective response rate (ORR) per BICR was 60% (95% CI, 55 to 65) with nivolumab plus chemotherapy versus 45% (95% CI, 40 to 50) with chemotherapy; median duration of response was 9.6 months (95% CI, 8.2 to 12.4) versus 7.0 months (95% CI, 5.6 to 7.9), respectively. Nivolumab plus chemotherapy also continued to show improvement in OS, PFS, and ORR versus chemotherapy in the overall population. Adding nivolumab to chemotherapy maintained clinically meaningful long-term survival benefit versus chemotherapy alone, with an acceptable safety profile, supporting the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastroesophageal adenocarcinoma.
Topics: Humans; Esophageal Neoplasms; Adenocarcinoma; Stomach Neoplasms; Nivolumab; Esophagogastric Junction; Antineoplastic Combined Chemotherapy Protocols; Male; Follow-Up Studies; Female; Aged; Middle Aged; Progression-Free Survival; Adult
PubMed: 38382001
DOI: 10.1200/JCO.23.01601 -
Journal of Yeungnam Medical Science Jul 2023Thallium poisoning is usually accidental. We present a case of a 51-year-old woman who was evaluated in June 2018 for myalgia, vertigo, asthenia, and abdominal pain....
Thallium poisoning is usually accidental. We present a case of a 51-year-old woman who was evaluated in June 2018 for myalgia, vertigo, asthenia, and abdominal pain. Physical examination revealed temporal-spatial disorientation, jaundice, and asterixis. The laboratory reported the following: bilirubin, 10.3 mg/dL; aspartate transaminase, 78 U/L; alanine transaminase, 194 U/L; albumin, 2.3 g/dL; prothrombin time, 40%; and platelet count, 60,000/mm3. Serology performed for hepatitis A, B, and C; Epstein-Barr virus; cytomegalovirus; and human immunodeficiency virus was negative, and a collagenogram was negative. Physical reevaluation revealed alopecia on the scalp, armpits, and eyebrows; macules on the face; plantar hyperkeratosis; and ulcers on the lower limbs. Tests for lead, arsenic, copper, and mercury were carried out, which were normal; however, elevated urinary thallium (540 µg/g; range, 0.4-10 µg/g) was observed. The patient was treated with ᴅ-penicillamine 1,000 mg/day and recovered her urinary thallium levels were within normal range at annual follow-up. Thallium poisoning is extremely rare and can be fatal in small doses. An adequate clinical approach can facilitate early diagnosis.
PubMed: 36537175
DOI: 10.12701/jyms.2022.00647 -
MSphere Mar 2024Members of , although typically opportunistic, can cause severe infections in immunocompromised hosts. Recent advances in genome sequencing provide an opportunity for...
UNLABELLED
Members of , although typically opportunistic, can cause severe infections in immunocompromised hosts. Recent advances in genome sequencing provide an opportunity for more precise study of this genus. In this study, we first identified and characterized a novel species named sp. nov. It has ≤88.23% average nucleotide identity (ANI) and ≤31.8% DNA-DNA hybridization (dDDH) values with all known species, which fall significantly below the species-defining thresholds. Interestingly, we found that and actually fall under the same species, evidenced by an ANI of 98.59% and a dDDH value of 90.4%. By fusing ANI with phylogeny, we have reclassified 545 genomes within this genus into 20 species, including seven unnamed taxa (provisionally titled Taxon 1-7), which can be further subdivided into 23 lineages. Pangenomic analysis identified 1,550 genus-core genes in , with coenzymes being the predominant category at 10.56%, suggesting significant intermediate metabolism activity. Resistance analysis revealed that most lineages of the genus (82.61%, 19/23) carry a high number of antibiotic-resistance genes (ARGs) and display diverse resistance profiles. Notably, the majority of ARGs are located on plasmids, underscoring the significant role of plasmids in the resistance evolution within this genus. Three species or lineages (, Taxon 3, and L12) that possess the highest number of carbapenem-resistance genes suggest their potential influence on clinical treatment. These findings underscore the need for continued surveillance and study of this genus, particularly due to their role in harboring antibiotic-resistance genes.
IMPORTANCE
The genus, known to harbor opportunistic pathogens, has been a subject of interest due to its potential to cause severe infections, particularly in vulnerable individuals. Our research offers groundbreaking insights into this genus, unveiling a novel species, sp. nov., and highlighting the need for a re-evaluation of existing classifications. Our comprehensive genomic assessment offers a detailed classification of 545 genomes into distinct species and lineages, revealing the rich biodiversity and intricate species diversity within the genus. The substantial presence of antibiotic-resistance genes in the genus underscores potential challenges for public health and clinical treatments. Our study highlights the pressing need for increased surveillance and research, enriching our understanding of antibiotic resistance in this realm.
Topics: Humans; Providencia; Plasmids; Anti-Bacterial Agents; Genomics; DNA
PubMed: 38412041
DOI: 10.1128/msphere.00731-23 -
Arquivos Brasileiros de Cardiologia 2024
PubMed: 38477765
DOI: 10.36660/abc.20230834 -
Healthcare (Basel, Switzerland) Oct 2023Adolescents have a greater risk of acquiring sexually transmitted infections (STIs), which is a serious public health problem. Education is an effective strategy to...
Adolescents have a greater risk of acquiring sexually transmitted infections (STIs), which is a serious public health problem. Education is an effective strategy to improve adolescent sexual health outcomes. However, Spanish adolescents have a lack of sex education. The aim of this study was to explore the perceptions and opinions of a sample of adolescents regarding sexually transmitted infections (STIs). Photovoice is a research method that uses the search for images of everyday events with the intention of bringing about social change. An exploratory, descriptive design was used with a qualitative approach based on the Photovoice methodology. The sample consisted of 26 high school and baccalaureate students of Almería (Spain) selected through a convenience sample. The age of the participants ranged from 14 to 17 years, with a mean age of 15.31 years. Two main categories were extracted from the data analysis: 'Towards a culture of preventing STIs and promoting healthy sexual practices' and 'Adolescents' needs from their perspective'. In conclusion, numerous changes take place at the biopsychosocial level during adolescence that imply a need to explore their sexuality in depth. A lack of knowledge and a carefree attitude during sexual initiation can increase the risk of developing STIs. The study's adolescents stated that they do not have adequate sex education to acquire sufficient knowledge about sexuality and sexual health, and therefore, request that the traditional format be modified in order to achieve better results.
PubMed: 37893831
DOI: 10.3390/healthcare11202757 -
Heliyon Jul 2023Achieving sustainability and resilience depends on the conciliation of environmental, social, and economic issues integrated into a long-term perspective to ensure...
Achieving sustainability and resilience depends on the conciliation of environmental, social, and economic issues integrated into a long-term perspective to ensure communities flourish. Many nations are transitioning toward both objectives, while at the same time addressing structural concerns that have not allowed them to look after the environment in the past. Chile is one of these nations dealing with such challenges within a particular administrative context, an increasing environmental awareness, and a set of unique and complex geophysical boundaries that impose a plethora of hazards for cities, ecosystems, and human health. This paper presents recent accomplishments and gaps, mostly from an environmental perspective, on issues related to air pollution, the urban water cycle, and soil contamination, in the path being followed by Chile toward urban sustainability and resilience. The focus is on the bonds between cities and their geophysical context, as well as the relationships between environmental issues, the built environment, and public health. The description and diagnosis are illustrated using two cities as case studies, Temuco and Copiapó, whose socioeconomic, geographical, and environmental attributes differ considerably. Particulate matter pollution produced by the residential sector, drinking water availability, wastewater treatment, stormwater management, and soil contamination from the mining industry are discussed for these cities. Overall, the case studies highlight how tackling these issues requires coordinated actions in multiple areas, including regulatory, information, and financial incentive measures. Finally, the policy analysis discusses frameworks and opportunities for Chilean cities, which may be of interest when conceiving transitional paths toward sustainability and resilience for other cities elsewhere.
PubMed: 37519708
DOI: 10.1016/j.heliyon.2023.e18191 -
Infection Dec 2023Antimicrobial resistance is a pressing issue in Ukraine, with healthcare-associated infections caused by multidrug-resistant organisms being a major concern. A recent...
Multidrug-resistant isolates from Ukrainian patients in a German health facility: a genomic surveillance study focusing on antimicrobial resistance and bacterial relatedness.
PURPOSE
Antimicrobial resistance is a pressing issue in Ukraine, with healthcare-associated infections caused by multidrug-resistant organisms being a major concern. A recent prospective multicenter study revealed a staggering rate of 48.4% antimicrobial resistance to carbapenems among Enterobacterales causing a healthcare-associated infection. We conducted a systematic survey to investigate the incidence rate and incidence density of carbapenemase-producing Gram-negative bacteria (CPGN) among refugees and war-wounded Ukrainians in connection with the German health system.
METHODS
From the onset of the war until November 2022, seven Ukrainian patients were admitted to our hospital. Upon admission, screening samples and samples from the focus of suspected infection were taken from all seven patients. The incidence rate and the incidence density of CPGN were calculated as a result of the microbiological findings. We sequenced all CPGN using Illumina technology.
RESULTS
The incidence rate of CPGN at our hospital was 0.06 for 2021 and 0.18 for 2022. All seven Ukrainian patients were infected or colonized with at least one CPGN, including K. pneumoniae (14/25), P. aeruginosa (6/25), A. baumannii (1/25), Providencia stutartii (1/25), C. freundii (1/25), and E. coli (2/25). Genomic surveillance revealed that (i) most frequently detected carbapenemases among all sequenced isolates were bla (17/25) and bla (6/25), (ii) most commonly observed plasmid replicons among the K. pneumoniae isolates recovered from Ukrainian patients were Col(pHAD28) (12/14), IncHI1B(pNDM-MAR) (9/14), IncFIB(pNDM-Mar) (12/14), and (iii) clonal relation between the pathogens of the Ukrainian isolates, but not for the isolates from our hospital surveillance system.
CONCLUSION
The rising prevalence of community-acquired colonization and infection with CPGN is having a direct effect on the infection prevention measures, such as higher number of isolations, reprocessing of patient rooms, additional microbiological testing and overall organization within hospitals.
Topics: Humans; Anti-Bacterial Agents; Escherichia coli; Drug Resistance, Bacterial; Microbial Sensitivity Tests; beta-Lactamases; Bacterial Proteins; Klebsiella pneumoniae; Cross Infection; Genomics
PubMed: 37338782
DOI: 10.1007/s15010-023-02061-4 -
Antibiotics (Basel, Switzerland) Jun 2023Mobile colistin resistance () genes (-1 to -10) are plasmid-encoded genes that threaten the clinical utility of colistin (COL), one of the highest-priority critically... (Review)
Review
Mobile Colistin Resistance () Gene-Containing Organisms in Poultry Sector in Low- and Middle-Income Countries: Epidemiology, Characteristics, and One Health Control Strategies.
Mobile colistin resistance () genes (-1 to -10) are plasmid-encoded genes that threaten the clinical utility of colistin (COL), one of the highest-priority critically important antibiotics (HP-CIAs) used to treat infections caused by multidrug-resistant and extensively drug-resistant bacteria in humans and animals. For more than six decades, COL has been used largely unregulated in the poultry sector in low- and middle-income countries (LMICs), and this has led to the development/spread of gene-containing bacteria (MGCB). The prevalence rates of -positive organisms from the poultry sector in LMICs between January 1970 and May 2023 range between 0.51% and 58.8%. Through horizontal gene transfer, conjugative plasmids possessing insertion sequences (ISs) (especially IS), transposons (predominantly Tn), and integrons have enhanced the spread of -1, -2, -3, -4, -5, -7, -8, -9, and -10 in the poultry sector in LMICs. These genes are harboured by , , , , , , , , , , , , and species, belonging to diverse clones. The -1, -3, and -10 genes have also been integrated into the chromosomes of these bacteria and are mobilizable by ISs and integrative conjugative elements. These bacteria often coexpress with virulence genes and other genes conferring resistance to HP-CIAs, such as extended-spectrum cephalosporins, carbapenems, fosfomycin, fluoroquinolone, and tigecycline. The transmission routes and dynamics of MGCB from the poultry sector in LMICs within the One Health triad include contact with poultry birds, feed/drinking water, manure, poultry farmers and their farm workwear, farming equipment, the consumption and sale of contaminated poultry meat/egg and associated products, etc. The use of pre/probiotics and other non-antimicrobial alternatives in the raising of birds, the judicious use of non-critically important antibiotics for therapy, the banning of nontherapeutic COL use, improved vaccination, biosecurity, hand hygiene and sanitization, the development of rapid diagnostic test kits, and the intensified surveillance of genes, among others, could effectively control the spread of MGCB from the poultry sector in LMICs.
PubMed: 37508213
DOI: 10.3390/antibiotics12071117