Infectious diseases (London, England)最新文献

Background: HIV-1-associated neurocognitive disorders (HAND) in stable patients undergoing antiretroviral therapy (ART) may result from ongoing immune dysregulation and chronic inflammation. A contributing factor may result from the unstable HLA class I allele, HLA-C*07.

Objective: To assess the genetic profile of killer-cell immunoglobulin-like receptors (KIR), human leukocyte antigens (HLA), and immune activation or senescence markers and their association with HAND in stable HIV-1 patients receiving ART.

Methods: An observational cross-sectional study was carried out with 96 patients with asymptomatic or symptomatic HAND. HLA and KIR as well as immune activation/senescence biomarkers in peripheral blood cells were assessed by SSO-Luminex typing and flow cytometry, respectively.

Results: HLA-C*07 is associated with symptomatic HAND. The frequency of two copies of HLA-C*07 was higher in patients with symptomatic than with asymptomatic HAND (12.0 vs. 2.2%, ρ < 0.001). The percentage of senescent CD8⁺CD28^- T-cells was higher in patients with two copies of HLA-C*07 (ρ < 0.05). In patients with symptomatic HAND, the percentages of non-senescent CD8⁺CD28⁺ T cells were inversely proportional to the number of copies of the HLA-C*07 (ρ < 0.05).

Conclusion: Patients with symptomatic HAND showed a higher frequency of the homozygotic unstable HLA-C*07 allotype, which could be associated with neurocognitive complications. Two copies of HLA-C*07 were associated with immune senescent T lymphocyte profiles characterized by the loss of CD28 expression.

The increasing global incidence of multidrug-resistant (MDR) bacterial infections threatens public health and compromises various aspects of modern medicine. Recognising the urgency of this issue, the World Health Organisation has prioritised the development of novel antimicrobials to combat ESKAPEE pathogens. Comprising Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli, such pathogens represent a spectrum of high to critical drug resistance, accounting for a significant proportion of hospital-acquired infections worldwide. In response to the waning efficacy of antibiotics against these resilient pathogens, phage therapy (PT) has emerged as a promising therapeutic strategy. This review provides a comprehensive summary of clinical research on PT and explores the translational journey of phages from laboratory settings to clinical applications. It examines recent advancements in pre-clinical and clinical developments, highlighting the potential of phages and their proteins, alone or in combination with antibiotics. Furthermore, this review underlines the importance of establishing safe and approved routes of phage administration to patients. In conclusion, the evolving landscape of phage therapy offers a beacon of hope in the fight against MDR bacterial infections, emphasising the imperative for continued research, innovation and regulatory diligence to realise its full potential in clinical practice.

Introduction: The assessment of Volatile Organic Compounds (VOCs) in exhaled breath or sweat represents a potential non-invasive and rapid diagnostic tool for respiratory diseases.

Objective: To determine if trained dogs can reliably identify the odour associated with COVID19.

Methods: This is a monocentric prospective study carried out in the Emergency Department (ED) of a university hospital fromJulyto November 2021.Axillary sweat samples from all patients were collected bytwo trained health care professionals. The samples were collected in the form of sterile gauze swabs placed under the armpits for at least 4 h for each patient.Then, Tubes wereshiftedto the double-blind dog training centre for VOC detection by two individuals.

Results: Dogs were tested using a total of 129 axillary sweat samples; 69 of the 107 patients who tested positive for COVID-19 based on their odours had a positive PCR/Antigen test and 19 of the 22 patients who were tested negative for COVID-19 by the dogs had a negative PCR test. The sniffer dog infection detection method had a sensitivity of 95.83% and a specificity of 33.33%. The PPV was 64.49% and the NPVwas 86.36%. The measurement of the intensity of the connection between the two variables (disease/sign) was very strong (Q = 0.84). This link is statistically significant (X² = 19.13) with a probability p ≤ 0.001.

Conclusion: Overall, the use of trained detection dogs as a screening method for SARS-CoV-2 is an interesting avenue of research that warrants further exploration and validation.

Cytomegalovirus (CMV) infection, which mostly causes a subclinical infection early in life, has important clinical consequences in certain patient groups. CMV is the most common congenital infection and can cause permanent disabilities such as hearing loss and motor- and cognitive deficits in affected infants. In allogeneic haematopoietic stem cell and solid organ transplant recipients, CMV still is an important infectious complication with a risk for life-threatening disease. The previous Swedish recommendations for the management of CMV infections were updated by an expert group under the guidance of The Swedish Reference Group for Antiviral Treatment (RAV) and published at the website of RAV in August 2023 (https://www.sls.se/rav/rekommendationer/cytomegalovirus/). We here provide a translation of the updated recommendations, with minor modifications regarding diagnosis of CMV pneumonia. In the present recommendations, we discuss aspects of old and new CMV antivirals, including dosing for different age groups, and cover the management of congenital infections and CMV in immunocompromised patients. The recommendations are evidence-graded in accordance with the Oxford Centre for Evidence-Based Medicine.

Purpose: This study aimed to present real-life data on the use, effectiveness, and safety of administering Ceftolozane/Tazobactam (C/T) through elastomeric pumps (EP) in the outpatient setting.

Methods: This case series study was conducted from January 2022 to July 2023 in a large University Hospital in Rome, Italy. Patients receiving continuous infusion of C/T via EP were included up to a follow-up period of 90 days after the end of antibiotic therapy. The primary endpoint was the infection's clinical cure rate. Secondary endpoints were adverse events attributable to continuous home infusion of Ceftolozane/Tazobactam via elastomeric pumps.

Results: Seven patients received C/T continuously infused via EP and were included in the final analysis. Three patients suffered from prosthetic joint infection (n = 3/7; 43%), two patients from osteomyelitis (n = 2/7; 29%), one patient from otomastoiditis (n = 1/7; 15%) and one from pneumonia (n = 1/7; 15%). All infection were sustained by P. aeruginosa. Five strains had MDR-type susceptibility profiles (n = 5/7; 71%) and two of these were DTR (n = 2/7; 29%). The infection cure rate reached 86% (n = 6/7). Two patients reported a complication related to the vascular catheter for drug infusion (n = 2/7; 29%).

Conclusions: Continuous infusion of Ceftolozane/Tazobactam by elastomeric pumps has been shown to be safe and effective in practice representing a viable option of intravenous treatment in outpatient setting for infection sustained by P. aeruginosa especially for multidrug-resistant strains.

Background: Systematic treatment with intravenous acyclovir is usually given when varicella zoster virus (VZV) DNA is isolated in cerebrospinal fluid (CSF), indicating central nervous system (CNS) involvement. Our study aimed to describe therapeutic management and acute kidney injury (AKI) occurrence during acyclovir treatment of VZV infection with CNS involvement.

Methods: Multicentre, retrospective study including all patients from 2010 to 2022 with VZV DNA in CSF. Patient management and outcomes were compared according to clinical presentation and indications for intravenous acyclovir: i) definite (encephalitis, myelitis or stroke, peripheral nervous system (PNS) with ≥ 2 roots, herpes zoster ≥ 3 dermatomes, immunosuppression), ii) questionable (1 or 2 dermatomes) or iii) no indication (other situations).

Results: 154 patients were included (median age 66 (interquartile range 43-77), 87 (56%) males); 60 (39%) had encephalitis, myelitis or stroke, 35 (23%) had PNS involvement, 37 (24%) had isolated meningitis, 14 (9%) had isolated cutaneous presentation, and 8 (5%) had other presentations. Overall, 128 (83%) received intravenous acyclovir for more than 72 h. AKI occurred in 57 (37%) patients. Finally, 42 (27%) and 25 (16%) patients had respectively no or a questionable indication for intravenous acyclovir, while 29 (69%) and 23 (92%) of them received it for more than 72 h, with AKI in 13 (35%) and 13 (52%) patients, respectively. In-hospital mortality was 12% (n = 18), and no deaths were reported in isolated meningitis.

Conclusions: Intravenous acyclovir is widely prescribed when VZV DNA is isolated in CSF, regardless of the clinical presentation, with a high rate of AKI. Further studies are needed to better define the value of intravenous acyclovir in isolated VZV meningitis.

Public health systems reported low mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in East Asia, in low-income countries, and for children during the first year of the SARS-CoV-2 pandemic. These reports led commentators to suggest that cross-reactive immunity from prior exposure to other pathogens reduced fatality risk. Resolution of initial infection waves also contributed to speculation that herd immunity prevented further waves prior to vaccination. Serology instead implied that immunity was too limited to achieve herd immunity and that there was little impact from cross-reactive protection. Paediatric deaths exceeded those from influenza, with higher age-specific fatality risk in lower-income nations and similar fatality risk in East Asia compared with demographically similar regions. Neither pre-outbreak exposure to related pathogens nor immunity induced by initial infection waves are necessarily a reliable response to future pathogen outbreaks. Preparedness for future pathogen outbreaks should instead focus on strategies such as voluntary behavioural changes, nonpharmaceutical interventions, and vaccination.

Background: There is a critical need for a rapid and sensitive pathogen detection method for septic patients. This study aimed to investigate the diagnostic efficacy of Digital droplet polymerase chain reaction (ddPCR) in identifying pathogens among suspected septic patients.

Methods: We conducted a prospective pilot diagnostic study to clinically validate the multiplex ddPCR panel in diagnosing suspected septic patients. A total of 100 sepsis episodes of 89 patients were included in the study.

Results: In comparison to blood culture, the ddPCR panel exhibited an overall sensitivity of 75.0% and a specificity of 69.7%, ddPCR yielded an additional detection rate of 17.0% for sepsis cases overall, with a turnaround time of 2.5 h. The sensitivity of ddPCR in the empirical antibiotic treatment and the non-empirical antibiotic treatment group were 78.6% versus 80.0% (p > 0.05). Antimicrobial resistance genes were identified in a total of 13 samples. Whenever ddPCR detected the genes beta-lactamase-Klebsiella pneumoniae carbapenemase (blaKPC) or beta-lactamase-New Delhi metallo (blaNDM), these findings corresponded to the cultivation of carbapenem-resistant gram-negative bacteria. Dynamic ddPCR monitoring revealed a consistent alignment between the quantitative ddPCR results and the trends observed in C-reactive protein and procalcitonin levels.

Conclusions: Compared to blood culture, ddPCR exhibited higher sensitivity for pathogen diagnosis in suspected septic patients, and it provided pathogen and drug resistance information in a shorter time. The quantitative results of ddPCR generally aligned with the trends seen in C-reactive protein and procalcitonin levels, indicating that ddPCR can serve as a dynamic monitoring tool for pathogen load in septic patients.