Expanding antibiotic, vaccine, and diagnostics development and access to tackle antimicrobial resistance

The Lancet, Год журнала: 2024, Номер 403(10443), С. 2534 - 2550

Опубликована: Май 23, 2024

Язык: Английский

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Review of Antimicrobial Properties of Titanium Dioxide Nanoparticles

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(19), С. 10519 - 10519

Опубликована: Сен. 29, 2024

There is a growing interest in the utilization of metal oxide nanoparticles as antimicrobial agents. This review will focus on titanium dioxide (TiO2 NPs), which have been demonstrated to exhibit high activity against bacteria and fungi, chemical stability, low toxicity eukaryotic cells, therefore biocompatibility. Despite extensive research conducted this field, there currently no consensus how enhance efficacy TiO2 NPs. The aim evaluate influence various factors, including particle size, shape, composition, synthesis parameters, well microbial type, antibacterial NPs fungi. Furthermore, offers comprehensive overview methodologies employed characterization exhibits weak dependence microorganism species. A tendency towards increased observed with decreasing NP size. shape composition more pronounced. most pronounced potential exhibited by amorphous doped inorganic compounds. may be specialists biology, medicine, chemistry, other related fields.

Язык: Английский

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Epidemiology of invasive Escherichia coli disease in adults in England, 2013–2017

Epidemiology and Infection, Год журнала: 2025, Номер 153

Опубликована: Янв. 1, 2025

Extraintestinal pathogenic

Язык: Английский

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Risk of Invasive Escherichia coli (E. coli) Disease After Elective Urologic Procedures Among Older Adults in the United States

Infectious Diseases and Therapy, Год журнала: 2025, Номер unknown

Опубликована: Фев. 7, 2025

Little is known about the risk of invasive E. coli disease (IED) after elective urologic procedures. We estimated IED selected procedures in patients with or without antibiotic prophylaxis, and controls no other surgical The Komodo Research Database (01/01/2021-06/30/2023) was used to identify ≥ 60 years old urological (index: first procedure date) randomly random date). Patients were classified into two cohorts based on whether not they received prophylaxis within 14 days prior index date. Entropy balancing adjusted for differences between groups patient characteristics over 6 months pre-index (baseline). rates 30 post-index assessed recorded diagnosis sepsis (ICD-10-CM: A41.51); odds ratios (OR) using weighted logistic regression. Sensitivity analyses 90 broader claims-based algorithm performed. Overall, 141,418 had 200,062 them 424,254 Within post-index, 0.48% 0.72% among respectively, vs. 0.02% those any Among procedures, > 70% events occurred days. who a higher developing than (OR = 1.50, 95% confidence interval [CI: 1.37-1.65]), while lower 0.04, CI [0.03-0.05]). Similar results obtained sensitivity analyses. Urologic associated an increased even prophylaxis. Results suggest unmet need additional preventative measures reduce burden

Язык: Английский

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Economic and Disease Burden Associated with Invasive Escherichia coli Disease in the United States

Infectious Diseases and Therapy, Год журнала: 2025, Номер unknown

Опубликована: Фев. 8, 2025

Invasive Escherichia coli disease (IED) incidence has increased over recent years among aging populations and rising antimicrobial resistance. Here, we report on a comparative, cross-sectional, retrospective analysis of US patients with IED to quantify IED-related healthcare resource utilization (HCRU), costs, impact health-related quality life (HRQoL). This study included Kaiser Permanente Northwest (KPNW) members aged ≥ 60 enrolled between July 2019 January 2020. Patients were divided into three groups: Group 1 had experienced episode (≤ 3 weeks before enrollment); 2 former (13–18 months was at risk no prior history IED. Data collected from electronic hospital records, patient survey, the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire. Mean costs adjusted according individual follow-up. Patient characteristics generally consistent across Groups (n = 289), 319), 340). Inpatient hospitalization observed in 84%, 44%, 15% 1, 3, respectively. direct per (per 30-day follow-up) $17,168, $2530, $1094 2, total year following an (Group 2) $35,034 vs. $16,163 at-risk 3. HRQoL poor for IED, mean EQ-5D-5L utility index value 0.25 worst day illness. During 12-month follow-up period, rehospitalization rates number antibiotic prescriptions ~ threefold higher who recovered those risk. These data demonstrate substantial short- long-term impacts HCRU, HRQoL. Additional research is needed further novel prevention strategies.

Язык: Английский

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Safety, Reactogenicity, Immunogenicity, and Dose Selection of 10-Valent Extraintestinal Pathogenic Escherichia coli Bioconjugate Vaccine (VAC52416) in Adults Aged 60–85 Years in a Randomized, Multicenter, Interventional, First-in-Human, Phase 1/2a Study

Open Forum Infectious Diseases, Год журнала: 2023, Номер 10(8)

Опубликована: Авг. 1, 2023

ExPEC10V is a bioconjugate vaccine containing O-antigen polysaccharides of 10 extraintestinal pathogenic Escherichia coli (ExPEC) serotypes. This phase 1/2a study (NCT03819049) assessed the safety, reactogenicity, and immunogenicity (VAC52416) to prevent invasive E disease in elderly adults.The observer-blind, active-controlled design included 28-day screening, vaccination, 181-day follow-up, 1-year follow-up. Participants (60-85 years age) were randomized low dose (antigen range, 4-8 µg), medium (4-16 or high (8-16 µg); 4-valent ExPEC (ExPEC4V); 13-valent pneumococcal conjugate (PCV13). The incidence adverse events (AEs; solicited, day 15; unsolicited, 30; serious AEs, 181) (electrochemiluminescent-based assay [ECL] multiplex opsonophagocytic [MOPA]) assessed. Optimal was determined from safety data through 30 an selection algorithm based on 15 ECL MOPA results.A total 416 participants (median age, 64.0 years; 54.8% female). incidences solicited local systemic AEs were, respectively, 44.2% 39.4% for low-dose, 52.9% 46.1% medium-dose, 57.7% 45.2% high-dose ExPEC10V, 74.1% 48.1% PCV13. Five not related, reported. revealed robust antibody response year 1. Opsonophagocytic killing activity detected against all but serotype O8; this lack O8 linked sensitivity. Based totality data, considered optimal.ExPEC10V well tolerated immunogenic adults O8.

Язык: Английский

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Clinical presentation and antimicrobial resistance of invasive Escherichia coli disease in hospitalized older adults: a prospective multinational observational study

Infection, Год журнала: 2024, Номер 52(3), С. 1073 - 1085

Опубликована: Янв. 25, 2024

Abstract Background Clinical data characterizing invasive Escherichia coli disease (IED) are limited. We assessed the clinical presentation of IED and antimicrobial resistance (AMR) patterns causative E. isolates in older adults. Methods EXPECT-2 (NCT04117113) was a prospective, observational, multinational, hospital-based study conducted patients with aged ≥ 60 years. determined by microbiological confirmation from blood; or urine an otherwise sterile body site presence requisite criteria systemic inflammatory response syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), quick SOFA (qSOFA). The primary outcomes were AMR rates to clinically relevant antibiotics. Complications in-hospital mortality through 28 days following diagnosis. Results Of 240 enrolled patients, 80.4% had bacteremic 19.6% non-bacteremic IED. One-half infections (50.4%) community-acquired. most common source infection urinary tract (62.9%). 65.8% fulfilled 2 SIRS criteria, 60.4% total score 2. Investigator-diagnosed sepsis septic shock reported 72.1% 10.0% respectively. complication kidney dysfunction (12.9%). overall 4.6%. 299 tested, were: 30.4% for trimethoprim-sulfamethoxazole, 24.1% ciprofloxacin, 22.1% levofloxacin, 16.4% ceftriaxone, 5.7% cefepime, 4.3% ceftazidime. Conclusions profile identified cases characterized high sepsis. associated identification can be optimized using combination (SIRS, SOFA, qSOFA) culture results.

Язык: Английский

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A randomized phase 1/2a trial of ExPEC10V vaccine in adults with a history of UTI

npj Vaccines, Год журнала: 2024, Номер 9(1)

Опубликована: Июнь 14, 2024

Abstract The safety, reactogenicity, and immunogenicity of 3 doses ExPEC10V (VAC52416), a vaccine candidate to prevent invasive Escherichia coli disease, were assessed in phase 1/2a study (NCT03819049). In Cohort 1, was well tolerated; the high dose selected as optimal further characterized 2. 2 comprised maximum 28-day screening, vaccination (Day 1), double-blind 181-day follow-up, open-label long-term follow-up until Year 1. Healthy participants (≥60 years) with history urinary tract infection (UTI) within 5 years randomized receive or placebo. primary endpoint evaluated safety reactogenicity (solicited local systemic AEs [until Day 15]; unsolicited 30], SAEs 181], [Day 30]) via multiplex electrochemiluminescent (ECL) opsonophagocytic assay (MOPA). 416 (ExPEC10V, n = 278; placebo, 138) included (mean age [SD], 68.8 [6.52] years; female, 79.6%; White, 96.1%). incidence solicited higher (local, 50.0% [ 139]; systemic, 139]) than placebo (15.9% 22]; 38.4% 53]); rates comparable 28.4% 79]; 26.1% 36]). No vaccine-related deaths reported. elicited robust antibody-mediated immunogenic response across all serotypes ECL 30 geometric mean fold increase, 2.33–8.18) demonstrated functional killing activity measured 1.81–9.68). exhibited an acceptable profile vaccine-induced UTI. Clinical trial registration details: https://clinicaltrials.gov/study/NCT03819049 .

Язык: Английский

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A microbiological and genomic perspective of globally collected Escherichia coli from adults hospitalized with invasive E. coli disease

Journal of Antimicrobial Chemotherapy, Год журнала: 2024, Номер 79(9), С. 2142 - 2151

Опубликована: Июль 13, 2024

Escherichia coli can cause infections in the urinary tract and normally sterile body sites leading to invasive E. disease (IED), including bacteraemia sepsis, with older populations at increased risk. We aimed estimate theoretical coverage rate by ExPEC4V 9V vaccine candidates. In addition, we better understanding diversity of isolates, their genetic phenotypic antimicrobial resistance (AMR), sequence types (STs), O-serotypes bacterial population structure.

Язык: Английский

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E. Coli cytotoxic necrotizing factor-1 promotes colorectal carcinogenesis by causing oxidative stress, DNA damage and intestinal permeability alteration

Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)

Опубликована: Янв. 29, 2025

Abstract Background Bacterial toxins are emerging as promising hallmarks of colorectal cancer (CRC) pathogenesis. In particular, Cytotoxic Necrotizing Factor 1 (CNF1) from E. coli deserves special consideration due to the significantly higher prevalence this toxin gene in CRC patients with respect healthy subjects, and numerous tumor-promoting effects that have been ascribed vitro. Despite evidence, a definitive causal link between CNF1 was missing. Here we investigated whether plays an active role onset by analyzing pro-carcinogenic key specifically induced vitro vivo. Methods Viability assays, confocal microscopy γH2AX 53BP1 molecules cytogenetic analysis were carried out assess CNF1-induced genotoxicity on non-neoplastic intestinal epithelial cells. Caco-2 monolayers 3D spheroids used evaluate permeability alterations CNF1, either presence or absence inflammation. vivo, inflammatory bowel disease (IBD) model exploited carcinogenic potential CNF1. Immunohistochemistry immunofluorescence stainings formalin-fixed paraffin-embedded (FFPE) colon tissue well fecal microbiota composition 16 S rRNA sequencing. Results induces release reactive oxidizing species chromosomal instability addition, modifies directly altering tight junctions’ distribution 2D monolayers, hindering differentiation irregular arrangement these junctions. repeated intrarectal administration formation dysplastic aberrant crypt foci (ACF), produces adenomas IBD model. These accompanied increased neutrophilic infiltration colonic tissue, mixed pro-inflammatory anti-inflammatory cytokine milieu, pro-tumoral modulation microbiota. Conclusions Taken together, our results support hypothesis carcinogenesis. Altogether, findings not only add new knowledge contribution bacterial CRC, but also pave way implementation current screening programs preventive strategies.

Язык: Английский

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