Metal natural product complex Ru-procyanidins with quadruple enzymatic activity combat infections from drug-resistant bacteria

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(5), P. 2298 - 2316

Published: Jan. 26, 2024

Bacterial infection hampers wound repair by impeding the healing process. Concurrently, inflammation at site triggers production of reactive oxygen species (ROS), causing oxidative stress and damage to proteins cells. This can lead chronic wounds, posing severe risks. Therefore, eliminating bacterial reducing ROS levels are crucial for effective healing. Nanozymes, possessing enzyme-like catalytic activity, convert endogenous substances into highly toxic substances, such as ROS, combat bacteria biofilms without inducing drug resistance. However, current nanozyme model with single enzyme activity falls short meeting complex requirements antimicrobial therapy. Thus, developing nanozymes multiple enzymatic activities is essential. Herein, we engineered a novel metalloenzyme called Ru-procyanidin nanoparticles (Ru-PC NPs) diverse aid infections. Under acidic conditions, due their glutathione (GSH) depletion peroxidase (POD)-like Ru-PC NPs combined H2O2 exhibit excellent antibacterial effects. in neutral environment, NPs, catalase (CAT) decompose O2, alleviating hypoxia ensuring sufficient supply. Furthermore, possess exceptional antioxidant capacity through superior superoxide dismutase (SOD) effectively scavenging excess nitrogen (RNS) environment. maintains balance system prevents inflammation. also promote polarization macrophages from M1 M2, facilitating More importantly, show good biosafety negligible toxicity. In vivo models have confirmed efficacy inhibiting promoting The focus this work highlights quadruple its potential reduce bacteria-infected

Language: Английский

---

Neonatal bacterial sepsis

The Lancet, Journal Year: 2024, Volume and Issue: 404(10449), P. 277 - 293

Published: June 26, 2024

Language: Английский

---

Ecological Consequences of Antibiotics Pollution in Sub-Saharan Africa: Understanding Sources, Pathways, and Potential Implications

Emerging contaminants, Journal Year: 2025, Volume and Issue: unknown, P. 100475 - 100475

Published: Jan. 1, 2025

Language: Английский

---

An Overview of Antibiotic Therapy for Early- and Late-Onset Neonatal Sepsis: Current Strategies and Future Prospects

Antibiotics, Journal Year: 2024, Volume and Issue: 13(3), P. 250 - 250

Published: March 10, 2024

Neonatal sepsis is a clinical syndrome mainly associated with bacterial infection leading to severe manifestations that could be fatal sequalae. According the time of onset, neonatal categorized as early- (EOS) or late-onset (LOS). Despite blood culture being gold standard for diagnosis, it has several limitations, and early diagnosis not immediate. Consequently, most infants who start empirical antimicrobial therapy do have an underlying infection. stewardship programs partially reduced this negative trend, in neonatology, antibiotic overuse still persists, relevant problems, first which increase resistance (AMR). Starting these considerations, we performed narrative review summarize main findings future prospects regarding antibiotics use treat sepsis. Because impact on morbidity mortality EOS LOS entail, essential effective prompt treatment soon possible. The targeted peremptory pathogen detected. Although essential, should better assessed whether, when how neonates antibiotics, even those at higher risk. Considering are certainly worrying era defined “post-antibiotic era”, urgent define novel strategies development antibacterial compounds new targets mechanisms action. A strategy also perform well-designed studies develop innovative algorithms improving etiological infection, allowing more personalized LOS.

Language: Английский

---

Antibiotics damage the colonic mucus barrier in a microbiota-independent manner

Science Advances, Journal Year: 2024, Volume and Issue: 10(37)

Published: Sept. 11, 2024

Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs). IBDs are characterized by damaged mucus layer, which does not separate the intestinal epithelium from microbiota. Here, we hypothesized that antibiotics affect integrity barrier, allows bacterial penetrance and predisposes to inflammation. We found antibiotic treatment led breakdown colonic barrier penetration bacteria into layer. Using fecal microbiota transplant, RNA sequencing followed machine learning, ex vivo secretion measurements, germ-free mice, determined induce endoplasmic reticulum stress in colon inhibits microbiota-independent manner. This antibiotic-induced flaw translocation microbial antigens circulation, exacerbation ulcerations mouse model IBD. Thus, might predispose inflammation impeding production.

Language: Английский

---

Baicalin restore intestinal damage after early-life antibiotic therapy: the role of the MAPK signaling pathway

Pharmacological Research, Journal Year: 2024, Volume and Issue: 204, P. 107194 - 107194

Published: April 23, 2024

Antibiotic related intestinal injury in early life affects subsequent health and susceptibility. Here, we employed weaned piglets as a model to investigate the protective effects of baicalin against early-life antibiotic exposure-induced microbial dysbiosis. Piglets exposed lincomycin showed marked reduction body weight (p < 0.05) deterioration jejunum morphology, alongside an increase antibiotic-resistant bacteria such Staphylococcus, Dolosicoccus, Escherichia-Shigella, Raoultella. In contrast, treatment resulted weights, profiles that closely resembled those control group > 0.05), with significant norank_f_Muribaculaceae Prevotellaceae_NK3B31_group colonization compared 0.05). Further analysis through fecal transplantation into mice revealed exposure led alterations morphology composition, notably increasing harmful microbes decreasing beneficial ones norank_Muribaculaceae Akkermansia This shift was associated metabolites disruption calcium signaling pathway gene expression. Conversely, supplementation not only counteracted these but also enhanced regulated genes within MAPK (MAP3K11, MAP4K2, MAPK7, MAPK13) channel proteins (ORA13, CACNA1S, CACNA1F CACNG8), suggesting mechanism which mitigates antibiotic-induced disturbances. These findings highlight baicalin's potential plant extract-based intervention for preventing antibiotic-related offer new targets therapeutic strategies.

Language: Английский

---

Antibiotic Use in Late Preterm and Full-Term Newborns

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(3), P. e243362 - e243362

Published: March 22, 2024

Importance Antibiotic treatment saves lives in newborns with early-onset sepsis (EOS), but unwarranted antibiotic use is associated resistant bacteria and adverse outcomes later life. Surveillance needed to optimize strategies. Objective To describe association the incidence mortality from EOS among late-preterm full-term newborns. Design, Setting, Participants The Sweden Neonatal Use study was a nationwide observational that included all neonates born January 1, 2012, December 31, 2020, neonatal units of levels. All hospital live births 34 weeks’ gestation during period were study. Data collected Swedish Quality Register Medical Birth Register. analyzed August 2022 May 2023. Exposure Admission for intensive care first week Main Outcomes Measures main usage intravenous antibiotics life, duration therapy, rate culture-proven EOS, EOS. Results A total 1 025 515 study; 19 286 (1.88%; 7686 girls [39.9%]; median [IQR] gestational age, 40 [38-41] weeks; birth weight, 3610 [3140-4030] g) received whom 647 (3.4%) had (IQR) without 5 (3-7) days, there 113 antibiotic-days per 1000 births. During no significant change exposure or 0.63 births, decrease 0.74 2012 0.34 2020. Mortality 1.39% (9 newborns) did not significantly over time. For each newborn initiated 29 173 dispensed. Conclusions Relevance This large found relatively low an increased risk mortality. Still, future efforts reduce are needed.

Language: Английский

---

Stop in Time: How to Reduce Unnecessary Antibiotics in Newborns with Late-Onset Sepsis in Neonatal Intensive Care

Tropical Medicine and Infectious Disease, Journal Year: 2024, Volume and Issue: 9(3), P. 63 - 63

Published: March 19, 2024

The fear of missing sepsis episodes in neonates frequently leads to indiscriminate use antibiotics, and prescription program optimization is suggested for reducing this inappropriate usage. While different authors have studied how reduce antibiotic overprescription the case early onset episodes, with approaches being available, less known about late-onset episodes. Biomarkers (such as C-reactive protein, procalcitonin, interleukin-6 8, presepsin) can play a crucial role prompt diagnosis sepsis, but their antimicrobial stewardship should be further studied, given that factors influence levels newborns subjected prolonged therapy if are expected return zero. To date, procalcitonin has best evidence performance sense, extrapolated from research on cases, more studies protocols biomarker-guided needed. Blood cultures (BCs) considered gold standard sepsis: positive BC rates neonatal workups been reported low, implying majority treated may receive unneeded drugs. New identification methods increase accuracy BCs guide de-escalation. after 36–48 h, negative baby clinically stable, antibiotics stopped. In narrative review, we provide summary current knowledge optimum approach pressure neonates.

Language: Английский

---

Antibiotic exposure for culture-negative early-onset sepsis in late-preterm and term newborns: an international study

Pediatric Research, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 17, 2024

Abstract Background Early-life antibiotic exposure is disproportionately high compared to the burden of culture-proven early-onset sepsis (CP-EOS). We assessed contribution culture-negative cases overall in first postnatal week. Methods conducted a retrospective analysis across eleven countries Europe, North America, and Australia. All late-preterm term infants born between 2014 2018 who received intravenous antibiotics during week were classified as treated for ≥5 days (CN ≥ 5d), <5 < or CP-EOS cases. Results Out 757,979 infants, 21,703 (2.9%) antibiotics. The number CN 5d, was 7996 (37%), 13,330 (61%), 375 (1.7%). incidence 10.6 (95% CI 10.3–10.8), 17.6 17.3–17.9), 0.49 0.44–0.54) per 1000 livebirths. median (IQR) administered 77 (77–78), 53 (52–53), 5 (5-5) Conclusions 5d substantially contributed exposure, 21-fold more frequent than CP-EOS. Antimicrobial stewardship programs should focus on shortening treatment Impact In study high-income countries, we report presumed 10.6/1000 livebirths with an associated This sheds light major early-life exposure. Given diagnostic uncertainty surrounding sepsis, low mortality rate, disproportionate this condition, our emphasizes importance targeting antimicrobial programs.

Language: Английский

---

National survey of sepsis proficiency in Swiss neonatal units

Intensive Care Medicine – Paediatric and Neonatal, Journal Year: 2025, Volume and Issue: 3(1)

Published: Jan. 8, 2025

Abstract Optimizing sepsis proficiency of healthcare professionals is key to improving outcomes. We aimed evaluate knowledge and management in neonatal units Switzerland. This cross-sectional survey, tailored profession, probed physician nurses’ self-assessment proficiency, definitions epidemiology, diagnostics seven nine tertiary care units. For points were given based on the accuracy answers diagnosis vignette clinical questions. Participants’ scores computed by summing expressed percent total available points. The questionnaire was completed 108/158 physicians (68.3%) 418/732 nurses (57.1%). Median 73.1% (Q1-Q3, 68.8–77.4%) 59.1% 52.3–65.9%). Physicians displayed an imbalance between self-assessment. Nurses a significant association self assessment but none with knowledge. A higher theoretical questions did not correlate decision-making (physicians: R = 0.13, 0.24). instance, while over 90% 80% recognized risk factors signs sepsis, actions prioritize, vignette, 22.2% 34.0% recognize need for antibiotics within 1 h extremely preterm newborn deterioration phlebitis around central line. identified gaps, better transduce into decision-making, potential improved Targeted simulation training could address these shortcomings.

Language: Английский

---