Mucoadhesive film for oral delivery of vaccines for protection of the respiratory tract.

The delivery of vaccines plays a pivotal role in influencing the strength and longevity of the immune response and controlling reactogenicity. Mucosal immunization, as compared to parenteral vaccination, could offer greater protection against respiratory infections while being less invasive. While oral vaccination has been presumed less effective and believed to target mainly the gastrointestinal tract, trans-buccal delivery using mucoadhesive films (MAF) may allow targeted delivery to the mucosa. Here we present an effective strategy for mucosal delivery of several vaccine platforms incorporated in MAF, including DNA plasmids, viral vectors, and lipid nanoparticles incorporating mRNA (mRNA/LNP). The mRNA/LNP vaccine formulation targeting SARS-CoV-2 as a proof of concept remained stable within MAF consisting of slowly releasing water-soluble polymers and an impermeable backing layer, facilitating enhanced penetration into the oral mucosa. This formulation elicited antibody and cellular responses comparable to the intramuscular injection, but also induced the production of mucosal IgAs, highlighting its efficacy, particularly for use as a booster vaccine and the potential advantage for protection against respiratory infections. The MAF vaccine preparation demonstrates significant advantages, such as efficient delivery, stability, and simple noninvasive administration with the potential to alleviate vaccine hesitancy.

Evaluation of resazurin-based rapid test to detect colistin resistance in Acinetobacter baumannii isolates.

Acinetobacter baumannii primarily causes colonization, yet it can be an opportunistic pathogen associated with hospital-acquired infections. Many countries report rapid spread of carbapenem-resistant Acinetobacter baumannii (CRAb) which limits treatment options, with colistin frequently being the last line treatment option. The aim of our study was to evaluate a recently developed rapid method, namely the Rapid ResaPolymyxin test, for detection of colistin resistance (ColR) in Acinetobacter baumannii. This test was used for rapid screening of colistin resistance in a clinical setting where there is endemicity of CRAb isolates. A total of 82 A. baumannii clinical isolates were included in the evaluation. The majority of them were resistant to carbapenems (75/82, 91.5%). A total of 37 isolates (45.1%) were resistant to colistin, all being resistant to carbapenems. None of the ColR isolates carried the plasmid-mediated mcr-1 to -5 genes. The Rapid ResaPolymyxin NP test reached a 95.1% categorical agreement with results of reference broth microdilution method, with 93.3% sensitivity and specificity, and positive and negative predictive values being respectively at 92.3% and 97.7%. The Rapid ResaPolymyxin NP test performed well on our collection of clinical and surveillance CRAb isolates from the Central Slovenia region. The test is inexpensive and easy to integrate into laboratory workflow. The main value of the test is rapid categorization of susceptibility and resistance which has important implications with respect to the treatment strategy as well as the infection control measures.

Portraying infective endocarditis: results of multinational ID-IRI study.

Infective endocarditis is a growing problem with many shifts due to ever-increasing comorbid illnesses, invasive procedures, and increase in the elderly. We performed this multinational study to depict definite infective endocarditis. Adult patients with definite endocarditis hospitalized between January 1, 2015, and October 1, 2018, were included from 41 hospitals in 13 countries. We included microbiological features, types and severity of the disease, complications, but excluded therapeutic parameters. A total of 867 patients were included. A total of 631 (72.8%) patients had native valve endocarditis (NVE), 214 (24.7%) patients had prosthetic valve endocarditis (PVE), 21 (2.4%) patients had pacemaker lead endocarditis, and 1 patient had catheter port endocarditis. Eighteen percent of NVE patients were hospital-acquired. PVE patients were classified as early-onset in 24.9%. A total of 385 (44.4%) patients had major embolic events, most frequently to the brain (n = 227, 26.3%). Blood cultures yielded pathogens in 766 (88.4%). In 101 (11.6%) patients, blood cultures were negative. Molecular testing of vegetations disclosed pathogens in 65 cases. Overall, 795 (91.7%) endocarditis patients had any identified pathogen. Leading pathogens (Staphylococcus aureus (n = 267, 33.6%), Streptococcus viridans (n = 149, 18.7%), enterococci (n = 128, 16.1%), coagulase-negative staphylococci (n = 92, 11.6%)) displayed substantial resistance profiles. A total of 132 (15.2%) patients had cardiac abscesses; 693 (79.9%) patients had left-sided endocarditis. Aortic (n = 394, 45.4%) and mitral valves (n = 369, 42.5%) were most frequently involved. Mortality was more common in PVE than NVE (NVE (n = 101, 16%), PVE (n = 49, 22.9%), p = 0.042).

Clinical appearance of Staphylococcus aureus spondylodiscitis and molecular characterization of the isolates.

Infectious spondylodiscitis is diagnosed with increasing frequency. It is most commonly caused by Staphylococcus aureus. The aim of the present study was to determine clinical differences between S. aureus and non-S. aureus spondylodiscitis and, by using spa typing, to determine whether certain clones of S. aureus predominate. During the y 2002-2006, 70 patients (45 male, 25 female) were diagnosed with spondylodiscitis and treated at the Department of Infectious Diseases, University Medical Centre Ljubljana. The age range was 13-95 y (mean age 63.4 y). Cultures were positive in 59 (85%) patients; S. aureus was isolated from blood and/or vertebral disc in 42 (60%) and other bacteria were isolated in 17 (25%). In patients with S. aureus spondylodiscitis, the infection was more likely to be haematogenous. These patients were more likely at risk for epidural abscess. Thirty S. aureus isolates from blood were typed with the spa typing molecular method. All of them were methicillin-susceptible. We identified 20 spa types. Seven spa types (t005, t015, t026, t091, t116, t449 and t474) were identified more than once, while 13 were sporadic. Among the sporadic spa types, 6 were newly identified in this study and introduced as new types into the spa server database. A heterogeneity of S. aureus isolates from spondylodiscitis was detected in this study. Thus no specific clone was identified that might be more likely to cause infection of the spine.

Primary cutaneous cryptococcosis in a renal transplant recipient: case report.

We report a kidney transplant recipient with severe skin- and soft-tissue infection mimicking necrotising fasciitis. Patient failed to respond to empirical antibiotic therapy for presumed bacterial cellulitis. Culture of aspirate from the wound and tissue samples revealed Cryptococcus neoformans. No signs of systemic cryptococcal infection were found. After antifungal treatment and surgical intervention, complete healing was achieved. Clinical and microbiological characteristics of this patient are discussed. Our case indicates that primary cutaneous cryptococcosis must be included in the differential diagnosis of severe cellulitis in solid organ transplant recipients not responding to broad-spectrum antibiotic regimens. In our case, prompt diagnosis and treatment could dramatically modify the outcome.