Patients with cystic fibrosis (CF) are prone to developing life-threatening lung infections with a variety of pathogens that are difficult to eradicate, such as Burkholderia cepacia complex (Bcc), Hemophilus influenzae, Mycobacterium abscessus (Mab), Pseudomonas aeruginosa, and Staphylococcus aureus. These infections still remain an important issue, despite the therapy for CF having considerably improved in recent years. Moreover, prolonged exposure to antibiotics in combination favors the development and spread of multi-resistant bacteria; thus, the development of alternative strategies is crucial to counter antimicrobial resistance. In this context, phage therapy, i.e., the use of phages, viruses that specifically infect bacteria, has become a promising strategy. In this review, we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients.

Renal vein thrombosis (RVT) is not an uncommon condition in patients occurring nephrotic syndrome. Renal cyst by bacterial infection is also rare. Only one case for RVT complicated with infected renal cyst is reported in the English literature. A 78-year-old female was admitted for fever and drowsy mentality for 4 days. Contrast-enhanced computed tomography (CECT) of the abdomen showed 3.7 cm sized irregular shaped exophytic cyst well enhanced in left kidney upper pole and the left RVT. The culture of cystic fluid revealed Klebsiella pneumoniae. Our patient was effectively treated with antibiotics for 8 weeks and anticoagulant for 12 weeks. At 12-week follow-up, CECT of the kidney showed decreased cyst and nearly disappeared RVT. The possibility of RVT in patients with renal cyst infection by bacteria warrants consideration.

Although the efficacy of treatment strategies for cancer have been improving steadily over the past decade, the adverse event profile following such treatments has also become increasingly complex. The present report described the case of a 67-year-old male patient with gastric stump carcinoma with liver invasion. The patient was treated with oxaliplatin and capecitabine (CAPEOX regimen) chemotherapy, combined with the programmed cell death protein-1 (PD-1) inhibitor tislelizumab. Following treatment, the patient suffered from chills, high fever and facial flushing, followed by shock. Relevant examination results revealed severe multiple organ damage, as well as a significant elevation in IL-6 and procalcitonin (PCT) levels. Initially, the patient was diagnosed with either immune-related adverse events (irAEs) associated with cytokine release syndrome caused by tislelizumab or severe bacterial infection. However, when tislelizumab treatment was stopped and the CAPEOX chemotherapy regimen was reapplied, similar symptoms recurred. Following screening, it was finally determined that severe hypersensitivity reaction (HSR) caused by oxaliplatin was the cause underlying these symptoms. A literature review was then performed, which found that severe oxaliplatin-related HSR is rare, rendering the present case atypical. The present case exhibited no common HSR symptoms, such as cutaneous and respiratory symptoms. However, the patient suffered from serious multiple organ damage, which was misdiagnosed as irAE when oxaliplatin chemotherapy combined with the PD-1 inhibitor was administered. In addition, this apparent severe oxaliplatin-related HSR caused a significant increase in PCT levels, which was misdiagnosed as severe bacterial infection and prevented the use of glucocorticoids. This, in turn, aggravated the damage in this patient.

Shigellosis is an enteric infection that transmits through the faecal-oral route, which can occur during sex between men who have sex with men (MSM). Between 2009 and 2014, an epidemic of sexually transmissible Shigella flexneri 3a occurred in England that subsequently declined. However, from 2019 to 2021, despite SARS-CoV-2 restrictions, S. flexneri 3a continued to re-emerge. We explored possible drivers of re-emergence by comparing host demography and pathogen genomics. Cases were primarily among 35-64 year old men in London. Genomic analyses of 502 bacterial isolates showed that the majority (58%) of re-emerging MSM strains were a clonal replacement of the original, with reduced antimicrobial resistance, conservation of plasmid col156_1, and two SNPs with 19 predicted effects. The absence of major changes in the pathogen or host demographics suggest that other factors may have driven the re-emergence of S. flexneri 3a and highlight the need for further work in the area.

BACKGROUND: Pneumonia due to typical bacterial, atypical bacterial and viral pathogens can be difficult to clinically differentiate. Host response-based diagnostics are emerging as a complementary diagnostic strategy to pathogen detection.
METHODS: We used murine models of typical bacterial, atypical bacterial and viral pneumonia to develop diagnostic signatures and understand the host\'s response to these types of infections. Mice were intranasally inoculated with Streptococcus pneumoniae, Mycoplasma pneumoniae, influenza or saline as a control. Peripheral blood gene expression analysis was performed at multiple time points. Differentially expressed genes were used to perform gene set enrichment analysis and generate diagnostic signatures. These murine-derived signatures were externally validated in silico using human gene expression data. The response to S. pneumoniae was the most rapid and robust.
RESULTS: Mice infected with M. pneumoniae had a delayed response more similar to influenza-infected animals. Diagnostic signatures for the three types of infection had 0.94-1.00 area under the receiver operator curve (auROC). Validation in five human gene expression datasets revealed auROC of 0.82-0.96.
CONCLUSIONS: This study identified discrete host responses to typical bacterial, atypical bacterial and viral aetiologies of pneumonia in mice. These signatures validated well in humans, highlighting the conserved nature of the host response to these pathogen classes.

Chronic wounds are susceptible to bacterial infections and at high risk of developing antibiotic-resistant bacterial infections. Silver is an antimicrobial by targeting almost all types of bacteria in chronic wounds to reduce the bacterial load in the infected area and further facilitate the healing process. This study focused on exploring whether silver-based dressings were superior to non-silver dressings in the treatment of chronic wounds. PubMed, Web of Science and Embase were comprehensively searched from inception to March 2024 for randomized clinical trials and observational studies. The endpoints in terms of wound healing rate, complete healing time, reduction on wound surface area and wound infection rate were analysed using Review Manager 5.4 software. A total of 15 studies involving 5046 patients were eventually included. The results showed that compared with patients provided with non-silver dressings, patients provided with silver-based dressings had higher wound healing rate (OR: 1.43, 95% CI: 1.10-1.85, p = 0.008), shorter complete healing time (MD: -0.96, 95% CI: -1.08 ~ -0.85, p < 0.00001) and lower wound infection rate (OR: 0.56, 95% CI: 0.40-0.79, p = 0.001); no significant difference in the reduction on wound surface area (MD: 12.41, 95% CI: -19.59-44.40, p = 0.45) was found. These findings suggested that the silver-based dressings were able to enhance chronic wound healing rate, shorten the complete healing time and reduce wound infection rate, but had no significant improvement in the reduction on wound surface area. Large-scale and rigorous studies are required to confirm the beneficial effects of silver-based dressings on chronic wound healing.

To maintain a clean and hygienic environment in the intensive care unit (ICU) is crucial for ensuring patient safety, preventing infections, and reducing healthcare-associated complications. With the increasing prevalence of infections and the emergence of viral and bacterial resistance to standard antiseptics, there is a pressing need for innovative antiseptic solutions. Nanotechnology is increasingly being employed in medicine, particularly focusing on mitigating the activities of various pathogens, including those associated with hospital-acquired infections. This paper explores the current impact of nanotechnology, with a particular focus on bacterial infections and SARS-CoV-2, which significantly strain healthcare systems, and then discusses how nanotechnology can enhance existing treatment methodologies. We highlight the effectiveness of the nanotechnology-based bactericide Bio-Kil in reducing bacterial counts in an ICU. The aim is to educate healthcare professionals on the existing role and prospects of nanotechnology in addressing prevalent infectious diseases.

Brain abscesses in ruminants often arise from primary infection foci, leading to an unfavorable prognosis for affected animals. This highlights the need for comprehensive studies on brain abscesses across different ruminant species. We retrospectively investigated medical records of epidemiological, clinical, neuroimaging, anatomopathological, and bacteriological findings in six ruminants (three goats, two cows, and one sheep) diagnosed with brain abscesses. All animals studied were female. Apathy (50%), compulsive walking (33%), decreased facial sensitivity (33%), head pressing (33%), seizures (33%), semicomatous mental status (33%), strabismus (33%), unilateral blindness (33%), and circling (33%) represented the most common neurologic signs. Leukocytosis and neutrophilia were the main findings in the hematological evaluation. Cerebrospinal fluid (CSF) analysis revealed predominant hyperproteinorrachia and pleocytosis. In three cases, computed tomography or magnetic resonance imaging were used, enabling the identification of typical abscess lesions, which were subsequently confirmed during postmortem examination. Microbiological culture of the abscess samples and/or CSF revealed bacterial coinfections in most cases. Advanced imaging examinations, combined with CSF analysis, can aid in diagnosis, although confirmation typically relies on postmortem evaluation and isolation of the causative agent. This study contributes to clinicopathological aspects, neuroimages, and bacteriological diagnosis of brain abscesses in domestic ruminants.

Skin damage is one of the most prevalent human injuries, which affects the health of human beings. However, skin damage is often accompanied by bacterial infection and wound microenvironment changes, causing damage to normal cells and inhibiting wound healing. Herein, we designed a thermal-responsive antibacterial hydrogel (GAG hydrogel) loaded with catalase (CAT)-like Au@Pt@MgSiO3 nanoparticles (APM NPs) and gentamicin (GM) to promote wound healing. The GAG hydrogel was used in a photothermal therapy (PTT)/antibiotic combination to kill bacteria, reduce the use of antibiotics, improve the wound microenvironment, promote cell proliferation, and accelerate wound healing. Under near-infrared laser irradiation, APM NPs in the hydrogel generated local hyperthermia to kill bacteria. Meanwhile, the generated heat led to a change in the hydrogel\'s morphology, enabling it to release GM and APM NPs to prevent the overuse of antibiotics. Subsequently, the CAT-like ability of the APM NPs decreased the oxidative stress caused by hydrogen peroxide (H2O2), thus remodeling the wound microenvironment. Then, the weakly acidic microenvironment of the wound caused the decomposition of the APM NPs and the release of magnesium ions (Mg2+), promoting the growth and migration of cells for wound healing. Therefore, the studied thermal-responsive antibacterial (GAG) hydrogel has potential in the field of wound healing.

SARS-CoV-2 infection was shown to induce proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma levels in sepsis. Here, we investigate the association between serum PCSK9 levels and disease severity. PCSK9 was measured in serum of 55 controls, 40 patients with moderate and 60 patients with severe COVID-19 disease. Serum PCSK9 was elevated in moderate COVID-19 compared to controls and further increased in severe cases. PCSK9 levels were not associated with C-reactive protein, bacterial superinfections, interventions, or survival in patients with severe COVID-19. PCSK9 regulates circulating cholesterol levels, and 15 cholesteryl ester (CE) species and free cholesterol (FC) were quantified by direct flow injection analysis using a high-resolution hybrid quadrupole-Orbitrap mass spectrometer. Most CE species with shorter fatty acid chains were decreased in severe compared to moderate COVID-19, and none of the CE species were correlated with PCSK9 in patients with severe COVID-19. Levels of all CE species negatively correlated with C-reactive protein in severe COVID-19 patients. Notably, FC was induced in severe compared to moderate COVID-19. The FC/CE ratio correlated positively with inflammatory markers and was associated with non-survival. The current study suggests that the imbalance between CE and FC levels is associated with disease severity and mortality in patients with COVID-19.