Site Infection Research Articles

A cell atlas of the adult female Aedes aegypti midgut revealed by single-cell RNA sequencing

Aedes aegypti is a primary vector for transmitting various arboviruses, including Yellow fever, dengue and Zika virus. The mosquito midgut is the principal organ for blood meal digestion, nutrient absorption and the initial site of arbovirus infection. Although a previous study delineated midgut’s transcriptome of Ae. aegypti at the single-nucleus resolution, there still lacks an established protocol for isolating and RNA sequencing of single cells of Ae. aegypti midgut, which is required for investigating arbovirus-midgut interaction at the single-cell level. Here, we established an atlas of the midgut cells for Ae. aegypti by single-cell RNA sequencing. We annotated the cell clusters including intestinal stem cells/enteroblasts (ISC/EB), cardia cells (Cardia), enterocytes (EC, EC-like), enteroendocrine cells (EE), visceral muscle (VM), fat body cells (FBC) and hemocyte cells (HC). This study will provide a foundation for further studies of arbovirus infection in mosquito midgut at the single-cell level.

Insertion site and risk of peripheral intravenous catheter colonization and/or local infection: a post hoc analysis of the CLEAN 3 study including more than 800 catheters

AimAlthough uncommon, infections associated with peripheral intravenous catheters (PIVCs) may be responsible for severe life-threatening complications and increase healthcare costs. Few data are available on the relationship between PIVC insertion site and risk of infectious complications.MethodsWe performed a post hoc analysis of the CLEAN 3 database, a randomized 2 × 2 factorial study comparing two skin disinfection procedures (2% chlorhexidine-alcohol or 5% povidone iodine-alcohol) and two types of medical devices (innovative or standard) in 989 adults patients requiring PIVC insertion before admission to a medical ward. Insertion sites were grouped into five areas: hand, wrist, forearm, cubital fossa and upper arm. We evaluated the risk of risk of PIVC colonization (i.e., tip culture eluate in broth showing at least one microorganism in a concentration of at least 1000 Colony Forming Units per mL) and/or local infection (i.e., organisms growing from purulent discharge at PIVC insertion site with no evidence of associated bloodstream infection), and the risk of positive PIVC tip culture (i.e., PIVC-tip culture eluate in broth showing at least one microorganism regardless of its amount) using multivariate Cox models.ResultsEight hundred twenty three PIVCs with known insertion site and sent to the laboratory for quantitative culture were included. After adjustment for confounding factors, PIVC insertion at the cubital fossa or wrist was associated with increased risk of PIVC colonization and/or local infection (HR [95% CI], 1.64 [0.92—2.93] and 2.11 [1.08—4.13]) and of positive PIVC tip culture (HR [95% CI], 1.49 [1.02—2.18] and 1.59 [0.98—2.59]).ConclusionPIVC insertion at the wrist or cubital fossa should be avoided whenever possible to reduce the risk of catheter colonization and/or local infection and of positive PIVC tip culture.

Advances in the targeted theragnostics of osteomyelitis caused by Staphylococcus aureus.

Bone infections caused by Staphylococcus aureus may lead to an inflammatory condition called osteomyelitis, which results in progressive bone loss. Biofilm formation, intracellular survival, and the ability of S. aureus to evade the immune response result in recurrent and persistent infections that present significant challenges in treating osteomyelitis. Moreover, people with diabetes are prone to osteomyelitis due to their compromised immune system, and in life-threatening cases, this may lead to amputation of the affected limbs. In most cases, bone infections are localized; thus, early detection and targeted therapy may prove fruitful in treating S. aureus-related bone infections and preventing the spread of the infection. Specific S. aureus components or overexpressed tissue biomarkers in bone infections could be targeted to deliver active therapeutics, thereby reducing drug dosage and systemic toxicity. Compounds like peptides and antibodies can specifically bind to S. aureus or overexpressed disease markers and combining these with therapeutics or imaging agents can facilitate targeted delivery to the site of infection. The effectiveness of photodynamic therapy and hyperthermia therapy can be increased by the addition of targeting molecules to these therapies enabling site-specific therapy delivery. Strategies like host-directed therapy focus on modulating the host immune mechanisms or signaling pathways utilized by S. aureus for therapeutic efficacy. Targeted therapeutic strategies in conjunction with standard surgical care could be potential treatment strategies for S. aureus-associated osteomyelitis to overcome antibiotic resistance and disease recurrence. This review paper presents information about the targeting strategies and agents for the therapy and diagnostic imaging of S. aureus bone infections.

Neuralgia Pasca Herpes

Herpes zoster, also known as snake pox and shingles , is a skin disease caused by reactivation of latent varicella zoster virus (VVZ) infection also known as human herpesvirus-3 (HHV-3) in the dorsal root sensory ganglion after primary infection. Mrs. A, 64 years old female was consulted with complaints of burning pain in the lower right abdomen to the right waist, that happened approximately 2 month after diagnosed with herpes zoster. Based on anamneses and physical examination the patient was diagnosed by Postherpetic neuralgia. Postherpetic neuralgia is persistent chronic pain and the most common complication in herpes zoster. In the majority of patients, pain from shingles is usually felt within 2 to 4 weeks. However, patients who experience NPH will experience continuous pain at the site of infection for 3 to 9 weeks after infection. The patients was given supportive treatment accompanied by education that can be provided to relieve the symptoms caused by this disease.

In vitro assessment of newer colistin-sparing antimicrobial agents for clinical isolates of carbapenem-resistant organisms

ObjectivesCarbapenem-resistant organisms (CROs) are a significant public health threat globally, particularly in countries like India with high antibiotic resistance rates. The current study investigates the prevalence of CROs, detects resistance mechanisms using phenotypic methods and assesses the efficacy of newer antibiotics against CROs. MethodsA prospective study conducted at a tertiary care hospital in India during 2021–23. Clinical specimens were processed and bacterial identification was performed using MALDI-TOF mass spectrometry followed by antimicrobial susceptibility testing using CLSI guidelines against a plethora of newer antibiotics for CROs. Carbapenemase production was detected using phenotypic methods, and the presence of the mcr-1 gene was assessed by real-time PCR. ResultsDuring the study period, predominantly (70 %) Gram-negative bacteria were isolated; amongst which 5692 strains were carbapenem-resistant, wherein resistance to different carbapenems ranged from 34.1% to 79 %. Majority of the carbapenemase producers were metallo-β-lactamases (MBL) producers (75 %). Colistin resistance was noted in 5.4 % of selected carbapenem-resistant isolates. Among newer antibiotics, cefiderocol demonstrated the lowest resistance rates (0–14 %), while resistance to newer β-lactam/β-lactamase inhibitor combinations was very high in carbapenem-resistant isolates. Fosfomycin, minocycline and tigecycline, each showing variable efficacy depending on the site of infection. Moreover, newer β-lactam/β-lactamase inhibitor combinations offer restricted benefits due to widespread prevalence of MBL in the region. ConclusionThe escalating prevalence of CROs in India underscores the urgency for alternative treatment options beyond colistin. Hence, highlighting the critical importance of developing effective strategies to combat carbapenem resistance.

Intestinal cDC1s provide cues required for CD4+ T cell-mediated resistance to Cryptosporidium.

Cryptosporidium is an enteric pathogen and a prominent cause of diarrheal disease worldwide. Control of Cryptosporidium requires CD4+ T cells, but how protective CD4+ T cell responses are generated is poorly understood. Here, Cryptosporidium parasites that express MHCII-restricted model antigens were generated to understand the basis for CD4+ T cell priming and effector function. These studies revealed that parasite-specific CD4+ T cells are primed in the draining mesenteric lymph node but differentiate into Th1 cells in the gut to provide local parasite control. Although type 1 conventional dendritic cells (cDC1s) were dispensable for CD4+ T cell priming, they were required for CD4+ T cell gut homing and were a source of IL-12 at the site of infection that promoted local production of IFN-γ. Thus, cDC1s have distinct roles in shaping CD4+ T cell responses to an enteric infection: first, to promote gut homing from the mesLN, and second, to drive effector responses in the intestine.

Role and significance of virus-bacteria interactions in disease progression.

Understanding disease pathogenesis caused by bacteria/virus, from the perspective of individual pathogen has provided meaningful insights. However, as viral and bacterial counterparts might inhabit the same infection site, it becomes crucial to consider their interactions and contributions in disease onset and progression. The objective of the review is to highlight the importance of considering both viral and bacterial agents during the course of coinfection. The review provides a unique perspective on the general theme of virus-bacteria interactions, which either lead to colocalized infections that are restricted to one anatomical niche, or systemic infections that have a systemic effect on the human host. The sequence, nature, and underlying mechanisms of certain virus-bacteria interactions have been elaborated with relevant examples from literature. It also attempts to address the various applied aspects, including diagnostic and therapeutic strategies for individual infections as well as virus-bacteria coinfections. The review aims to aid researchers in comprehending the intricate interplay between virus and bacteria in disease progression, thereby enhancing understanding of current methodologies and empowering the development of novel health care strategies to tackle coinfections.

Identifying and Evaluating Occupational Hazards of Infectious Waste Landfill Workers by the JHA Method

Background: In waste management, neglecting and mismanaging harmful biological factors can result in adverse consequences for both organizations and employees. Methods: This study aimed to identify and assess the health and safety risks faced by workers at an infectious waste site using the job hazard analysis (JHA) method. This cross-sectional descriptive study was conducted in 1401 at the waste disposal center "Halgheh Dareh" in Karaj. The JHA method involved dividing the job into tasks, identifying safety and health risks associated with each task, determining the probability and severity of the risks, and finally classifying them using a matrix based on the MIL-STD-882B standard. Control measures were also presented. All calculations were performed using Excel 2010. Results: The results revealed that out of the 20 risks analyzed, 40% were classified as unacceptable risks, 25% as undesirable risks, 30% as acceptable risks but in need of revision, and 5% as minor risks. Conclusion: Through the application of the JHA method, we were able to evaluate and classify health and safety risks according to their level of severity. By implementing control measures such as the use of personal protective equipment, periodic medical examinations, administration of the Hepatitis vaccine, and adherence to safety protocols, it is possible to reduce the risks and prevent the occurrence of occupational diseases and accidents that can lead to harm.

Cefiderocol for treating severe aerobic Gram-negative bacterial infections: technology evaluation to inform a novel subscription-style payment model.

To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of cefiderocol in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform the National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England. The health benefit of cefiderocol was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients' mortality risks and health-related quality of life. The clinical effectiveness of cefiderocol relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. Patient-level costs and health outcomes of cefiderocol under various usage scenarios compared with alternative management strategies were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population values using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for cefiderocol. Among Enterobacterales isolates with the metallo-beta-lactamase resistance mechanism, the base-case network meta-analysis found that cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.32, 95% credible intervals 0.04 to 2.47), but the result was not statistically significant. The other treatments were also associated with lower susceptibility than colistin, but the results were not statistically significant. In the metallo-beta-lactamase Pseudomonas aeruginosa base-case network meta-analysis, cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.44, 95% credible intervals 0.03 to 3.94), but the result was not statistically significant. The other treatments were associated with no susceptibility. In the base case, patient-level benefit of cefiderocol was between 0.02 and 0.15 quality-adjusted life-years, depending on the site of infection, the pathogen and the usage scenario. There was a high degree of uncertainty surrounding the benefits of cefiderocol across all subgroups. There was substantial uncertainty in the number of infections that are suitable for treatment with cefiderocol, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time and rates of emergence of resistance. The population-level benefits varied substantially across the base-case scenarios, from 896 to 3559 quality-adjusted life-years over 20 years. This work has provided quantitative estimates of the value of cefiderocol within its areas of expected usage within the NHS. Given existing evidence, the estimates of the value of cefiderocol are highly uncertain. Future evaluations of antimicrobials would benefit from improvements to NHS data linkages; research to support appropriate synthesis of susceptibility studies; and application of routine data and decision modelling to assess enablement value. No registration of this study was undertaken. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Policy Research Programme (NIHR award ref: NIHR135591), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in Health Technology Assessment; Vol. 28, No. 28. See the NIHR Funding and Awards website for further award information.

Comparative Evaluation of Microhardness and Solubility of Different Combinations of Antibiotic Powders Added to Glass Ionomer Cement: An In Vitro Study.

The imbalance between remineralization and demineralization leads to the formation of secondary caries. Fluoride-releasing ability has been the characteristic property of glass ionomer cement (GIC), but it is uncertain if this property alone will be sufficient for the cessation of the growth of the organisms. Therefore, a restorative material with additional bacteriostatic properties needs to be introduced. To evaluate the microhardness and solubility of the conventional GIC after adding different combinations of antibiotic powders. In this study, the three groups were conventional GIC (group I), GIC + metronidazole + ciprofloxacin (group II), and GIC + metronidazole + amoxicillin/clavulanic acid (group III). The concentration of the double antibiotic combination was maintained at 1.5% w/w. The antibiotic powders were added to the GIC and evaluated for microhardness and solubility of the specimens. The mean microhardness level of group II was the highest, which was statistically significant using analysis of variance (ANOVA) with a p-value of 0.022. The comparison of each group's solubility in different solutions was not statistically significant. Along with the conventional properties of GIC, an additional therapeutic gain can also be obtained by incorporating various combinations of antibiotics, thereby arresting the progression of caries at the site of infection itself. This new approach shall help in community health programs, where treatment of a large population needs to be done within a short span of time and arrest the progression of caries activity in deep caries. Benson TL, Sogi S, Jain M, et al. Comparative Evaluation of Microhardness and Solubility of Different Combinations of Antibiotic Powders Added to Glass Ionomer Cement: An In Vitro Study. Int J Clin Pediatr Dent 2024;17(6):619-624.

Comparison of Infection Risks Between Various Inhaled and Intranasal Corticosteroids: A Pharmacovigilance Analysis Based on the FAERS Database.

This study conducted a pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) database to compare the infection risk of inhaled or nasal Beclomethasone, Fluticasone, Budesonide, Ciclesonide, Mometasone, and Triamcinolone Acetonide. We used proportional imbalance analysis to evaluate the correlation between ICS /INCs and infection events. The data was extracted from the FAERS database from April 2015 to September 2023. Further analysis was conducted on the clinical characteristics, site of infection, and pathogenic bacteria of ICS and INCs infection adverse events (AEs). We used bubble charts to display their top 5 infection adverse events. We analyzed 21,837 reports of infection AEs related to ICS and INCs, with an average age of 62.12 years. Among them, 61.14% of infection reports were related to females. One-third of infections reported to occur in the lower respiratory tract with Fluticasone, Budesonide, Ciclesonidec, and Mometasone; over 40% of infections reported by Triamcinolone Acetonide were eye infections; the rate of oral infections caused by Beclomethasone were 7.39%. The reported rates of fungal and viral infections caused by beclomethasone were 21.15% and 19.2%, respectively. The mycobacterial infections caused by Budesonide and Ciclesonidec account for 3.29% and 2.03%, respectively. Bubble plots showed that the ICS group had more fungal infections, oral infections, pneumonia, tracheitis, etc. The INCs group had more eye symptoms, rhinitis, sinusitis, nasopharyngitis, etc. Women who use ICS and INCs are more prone to infection events. Compared to Budesonide, Fluticasone seemed to have a higher risk of pneumonia and oral candidiasis. Mometasone might lead to more upper respiratory tract infections. The risk of oral infection was higher with Beclomethasone. Beclomethasone causes more fungal and viral infections, while Ciclesonide and Budesonide are more susceptible to mycobacterial infections.

Correlation Analysis between STING Promoter Polymorphism and Susceptibility to Infection after Chemotherapy for Multiple Myeloma

To investigate the correlation between the stimulator of interferon genes (STING ) promoter polymorphism and the susceptibility to infection after chemotherapy for multiple myeloma. A total of 102 patients who had undergone chemotherapy for multiple myeloma in our hospital from January 2016 to July 2022 were selected. Depending on the presence or absence of infection after chemotherapy, the enrolled patients were divided into infection group (53 cases) and non-infection group (49 cases). The infection sites and distribution characteristics of pathogenic bacteria of the infection group were analyzed. The genotype distribution of STING gene promoter rs587777609 was compared between the two groups, and the risk factors of infection after chemotherapy for multiple myeloma were analyzed. For infection site, digestive system, respiratory system, urinary system, skin and mucous membranes accounted for 43.40%, 26.42%, 20.75%, and 9.43%, respectively. For pathogenic bacteria, Gram-negative bacteria, Gram-positive bacteria and fungi accounted for 57.14%, 26.98%, and 15.87%, respectively. The CC genotype frequency of STING gene rs587777609 locus in the infection group was lower than that in the non-infection group, while the TT genotype frequency was higher than that in the non-infection group (P < 0.05). The proportions of patients with diabetes, chronic obstructive pulmonary disease, renal insufficiency, serum albumin level< 35 g/L, ISS stage III, mechanical ventilation, and indwelling catheter in the infection group were higher than those in the non-infection group (P < 0.05). Multivariate logistic regression analysis showed that diabetes (OR =1.992), serum albumin level< 35 g/L (OR =2.782), ISS stage III (OR =2.707), mechanical ventilation (OR =3.031), and TT genotype (OR =2.401) were risk factors of infection after chemotherapy for multiple myeloma (P < 0.05). There is a correlation between STING promoter polymorphism and the susceptibility to infection after chemotherapy for multiple myeloma, and patients with TT genotype have a higher risk of infection.

Impact of buried versus exposed flexible intramedullary nails osteosynthesis on pediatric forearm fractures

To determine the risk of re-fracture in patients with a nail buried directly into the amr or left exposed as a treatment for forearm fractures, and to investigate postoperative complications. The study included 113 pediatric patients with a forearm fracture of both diaphyses. Two groups were formed according to whether the nail was buried (Group B, n: 53) in the same arm or left exposed (Group E, n: 60). Data on the number of open reductions, the time to nail removal, the anesthesia type used for its removal, the number of re-fractures, skin infection, and nail entry site irritation were analyzed. The mean union times between the groups were not significantly different (P = 0.371). The mean time of nail removal in group B (16.02 ± 1.29 weeks) was significantly longer than that of group E (6.65 ± 0.95 weeks) (P < 0.001). Open reduction rates were similar between groups (P = 0.401). The general anesthesia rate for nail removal in group B (77.4%) was significantly higher than group E (11.7%) (P < 0.001). The re-fracture rate was higher in patients who underwent open reduction in both groups (P < 0.001). The results of this study demonstrated that, despite the increased infection rate, leaving the nail exposed did not increase the re-fracture rate, which was associated with open reduction.

Rapid high-throughput method for investigating physiological regulation of neutrophil extracellular trap formation

BackgroundNeutrophils, the most abundant white blood cells in humans, play pivotal roles in innate immunity, rapidly migrating to sites of infection and inflammation to phagocytose, neutralize, and eliminate invading pathogens. Neutrophil extracellular trap (NET) formation is increasingly recognized as an essential rapid innate immune response, but when dysregulated, it contributes to pathogenesis of sepsis and immunothrombotic disease. ObjectivesCurrent NETosis models are limited, routinely employing nonphysiological triggers that can bypass natural NET regulatory pathways. Models utilizing isolated neutrophils and immortalized cell lines do not reflect the complex biology underlying neutrophil activation and NETosis that occurs in whole blood. To our knowledge, we report the first human ex vivo model utilizing naturally occurring molecules to induce NETosis in whole blood. This approach could be used for drug screening and, importantly, inadvertent activators of NETosis. MethodsHere we describe a novel, high-throughput ex vivo whole blood–induced NETosis model using combinatorial pooling of native NETosis-inducing factors in a more biologically relevant Synthetic-Sepsis model. ResultsWe found different combinations of factors evoked distinct neutrophil responses in the rate of NET generation and/or magnitude of NETosis. Despite interdonor variability, similar sets of proinflammatory molecules induced consistent responses across donors. We found that at least 3 biological triggers were necessary to induce NETosis in our system including either tumor necrosis factor-α or lymphotoxin-α. ConclusionThese findings emphasize the importance of investigating neutrophil physiology in a biologically relevant context to enable a better understanding of disease pathology, risk factors, and therapeutic targets, potentially providing novel strategies for disease intervention and treatment.

Clinical classification, staging and treatment strategy of radionecrosis of the nasopharynx and skull base

Objective:To establish a staging system for guiding clinical treatment and prognostic risk assessment by retrospectively analyzing the cases with radionecrosis of the nasopharynx and skull base （RNSB） after radiotherapy for nasopharyngeal carcinoma. Methods:A total of 86 cases of RNSB from January 2019 to December 2022 visited Department of Otorhinolaryngology Head and Neck, the People's Hospital of Guangxi Zhuang Autonomous Region. Seventeen patients gave up the treatment, and 69 patients who underwent treatment were included for analysis. By analyzing the results of electronic nasopharyngolaryngoscopy combined with magnetic resonance （MR）, CT, and other imaging examinations, a staging system for RNSB was proposed. The relationship between the staging system and the surgical effectiveness and clinical prognosis was further analyzed. Results:According to the severity and extent of destruction of soft tissue, bone, and the adjacent neurovascular structures, the RNSB was categorized into closed type （n=5） and open type （n=64）, of which the open type was subdivided into five types: type Ⅰ（n=4）, type Ⅱ（n=6）, type Ⅲ（n=39, of which 21 cases were type Ⅲa and 18 cases were type Ⅲb）, type Ⅳ（n=12）, and type Ⅴ（n=8）. The clinical stage of RNSB were classified based on nasopharyngolaryngoscopy and imaging examinations, receiving the second course of radiotherapy or not, the involvement of the infection site, the extent of bone destruction, the degree of internal carotid artery involvement, and the degree of brain tissue necrosis: stageⅠ（1-2 scores）, 11 cases at stageⅡ（3-4 scores）, 24 cases at stage Ⅲ（5-6 scores）, and 30 cases at stage Ⅳ（ ≥ 7 scores or more）. Twenty-two patients chose conservative treatment （2 patients at stage Ⅰ, 3 patients at stage Ⅱ, 7 patients at stage Ⅲ, and 10 patients at stage Ⅳ）. Forty-seven patients chose nasal endoscopic surgical treatment （2 patients at stage Ⅰ, 8 patients at stage Ⅱ, 17 patients at stage Ⅲ, and 20 patients at stage Ⅳ）, of which 16 cases had received free mucosal flap and/or stented septum mucosal flap repair. Patients at stages Ⅰ, Ⅱ, and Ⅲ achieved satisfactory efficacy after surgical treatment. In addition, higher clinical stage was found to correlate with the worse prognosis and higher incidence of perioperative complications, which included failure of healing because of surgical site infection, cerebrospinal fluid nasal leakage, progressive osteonecrosis, nasopharyngeal hemorrhage, and death. Conclusion:The staging system proposed in our study can be used for early detection of RNSB during regular follow-up, and is also valuable for clinical treatment guidance and prognosis assessment.

In Vitro Lethality of Fenbendazole to the Eyeworm Oxyspirura petrowi.

Oxyspirura petrowi is a heteroxenous nematode that infects the harderian gland and other ocular tissues in birds. High-intensity infections often cause damage to the infected tissues. Due to the nature of the infection sites, treatment of O. petrowi in these hosts can be difficult. Fenbendazole (FBZ) is a common anthelmintic used to treat birds for helminth infections; however, little information exists as to the efficacy of the drug on O. petrowi infections. The present study aims to estimate lethal concentrations of FBZ to O. petrowi. Adult O. petrowi were maintained in vitro and exposed to doses of 5, 50, 100, and 200 µM concentrations of FBZ and included both negative and vehicle controls. Exposure lasted 7.5 days and lethality was determined for each treatment. Negative and vehicle controls did not differ, and both had 75% survival at the end of the treatment period. The percentage survivorship in ascending order of concentration, corrected for the controls, was 66.67%, 44.44%, 33.33%, and 0%. LC10, LC50, and LC90 estimates were 7.5 ± 0.26, 49.1 ± 1.69, and 163.2 ± 5.63 µM, respectively. In the context of known pharmacokinetics of FBZ in birds, a single oral dose of FBZ can achieve exposure levels that are lethal to O. petrowi, but the drug does not stay in the system long enough. Thus, treatment of O. petrowi infections will require multiple oral doses over several days.

Frequency, characteristics, and outcome of adult patients with multiple consecutive health care-associated infections undergoing extracorporeal membrane oxygenation: A retrospective analysis

Data on multiple consecutive health care-associated infections (HAIs) in patients undergoing extracorporeal membrane oxygenation (ECMO) are limited. We aim to identify the characteristics and outcomes of multiple, consecutive HAIs. This retrospective study included adult patients who underwent ECMO in a single cardiac ICU in China from May 2015 to December 2022. The incidence, clinical characteristics, risk factors, and impact on in-hospital mortality among patients with non-HAI, single HAI, and multiple HAIs were analyzed. Pathogens and infection sites for each new episode were compared. Of 192 patients, 92 (47.92%) developed 141 separate infections, with 41 (21.35%) experiencing multiple infections during a single ECMO period. Respiratory tract infections (RTIs) constituted the majority (75.89%), and gram-negative bacteria were the predominant pathogens (71.63%). RTIs decreased from 86.9% in the first infection to 14.3% in the third (P<.001), while bloodstream infections increased from 10.9% to 57.1% (P<.001). The proportion of gram-positive bacteria increased from 9.8% to 42.9% (P=.032). Prolonged ECMO duration was the only independent risk factor for multiple consecutive HAIs (odds ratio (OR)=1.220,P<.001). Multiple consecutive HAIs during ECMO were frequent, with distinct microbiological changes between initial and subsequent HAIs.

Diagnostic and Prognostic Ability of Pancreatic Stone Protein: A Scoping Review.

Pancreatic stone protein (PSP) is an acute-phase reactant mainly produced in response to stress. Its diagnostic and prognostic accuracy for several types of infection has been studied in several clinical settings. The aim of the current review was to assess all studies examining a possible connection of pancreatic stone protein levels with the severity and possible complications of patients diagnosed with infection. We performed a systematic search in PubMed, Scopus, the Cochrane Library and Clinicaltrials.gov to identify original clinical studies assessing the role of pancreatic stone protein in the diagnosis and prognosis of infectious diseases. We identified 22 eligible studies. Ten of them provided diagnostic aspects, ten studies provided prognostic aspects, and another two studies provided both diagnostic and prognostic information. The majority of the studies were performed in an intensive care unit (ICU) setting, five studies were on patients who visited the emergency department (ED), and three studies were on burn-injury patients. According to the literature, pancreatic stone protein has been utilized in patients with different sites of infection, including pneumonia, soft tissue infections, intra-abdominal infections, urinary tract infections, and sepsis. In conclusion, PSP appears to be a useful point-of-care biomarker for the ED and ICU due to its ability to recognize bacterial infections and sepsis early. Further studies are required to examine PSP's kinetics and utility in specific populations and conditions.

Inappropriate use of antibiotic enhances antibiotic resistance dissemination in ESBL-EC: Role of ydcz in outer membrane vesicles biogenesis and protein transport

Extended-spectrumβ-lactam producing Escherichia coli (ESBL-EC) readily colonizes live poultry and serves as a major source of contamination in retail chicken meat, posing significant threats to public health. This study aims to investigate the impact of inappropriate antibiotic use on the dissemination and exacerbation of antibiotic resistance in ESBL-EC and explore the underlying molecular mechanisms. Through experimental analysis, we propose a hypothesis that inappropriate antibiotic use may exacerbate resistance by affecting vesicle formation and protein secretion. Experimental results demonstrate that under the influence of amoxicillin, the concentration of proteins secreted in outer membrane vehicles (OMVs) by ESBL-EC significantly increases, along with a significant upregulation in the expression of the CTX-M-55-type Extended-spectrum beta-lactamase (CTX-M-55). Proteomic analysis and differential gene knockout experiments identified the key protein YdcZ, associated with OMVs formation and protein transportation in ESBL-EC under amoxicillin treatment. Further investigations reveal direct interactions between YdcZ and other proteins (YdiH and BssR). Upon ydcz gene knockout, a significant decrease in protein concentration within OMVs is observed, accompanied by a noticeable reduction in protection against sensitive bacteria. These findings suggest a critical role of YdcZ in regulating the process of protein transportation to OMVs in ESBL-EC under the influence of amoxicillin. In summary, our research uncovers the significant role of inappropriate antibiotic use in promoting the secretion of OMVs by ESBL-EC, aiding the survival of antibiotic-sensitive bacteria in the vicinity of infection sites. These findings provide new insights into the mechanisms underlying antibiotic-induced bacterial resistance dissemination and offer novel avenues for exploring prevention and control strategies against bacterial resistance propagation.

Low-grade inflammation in the post-COVID period as a strategic goal of treatment and rehabilitation

As of the beginning of 2023, there are more than 660 million convalescents of a new coronavirus infection in the world, however, even despite successful treatment of the acute period of the disease, such patients have a high risk of developing long-term complications in the post-COVID period, primarily cardiovascular events. One factor that seriously increases the risk of these complications is the state of lowgrade systemic inflammation (LGSI). LGSI is not a clinical diagnosis, it is characterized by a level of C-reactive protein in peripheral blood in the range of 3–10 mg/l and is most often detected during routine examination of patients, who in most cases have no clinical symptoms. In this regard, the condition of LGSI most often remains unnoticed and unreasonably ignored, despite quite extensive literature data on the effect of LGSI on the pathogenesis of many cardiovascular diseases. The development of drug therapy for LGSI is complicated by the multifactorial etiology of this condition. The causes of LGSI can be both genetic factors, which are practically impossible to correct, and conditions that are amenable to drug and non-drug treatment, such as, for example, increased intestinal permeability to pro-inflammatory agents, including lipopolysaccharide of gram-negative flora, the presence of a chronic untreated infection site and endocrine pathology (obesity and type 2 diabetes). This review presents the main information to date on the state of LGSI in patients who had a new coronavirus infection, including the results of our own observations of patients who have undergone a course of rehabilitation measures, as well as the most significant, in our opinion, factors predisposing to the development of LGSI in such patients.