Assessing the Influence of Urine pH on the Efficacy of Ciprofloxacin and Fosfomycin in Immunocompetent and Immunocompromised Murine Models of and Infection in the Lower Urinary Tract.

In vitro studies have suggested that acidic pH may reduce and increase the efficacy of ciprofloxacin and fosfomycin, respectively, when used to treat and infections. We assessed the effects of acidic, neutral, and alkaline urine pH on the efficacy of optimized ciprofloxacin and fosfomycin dosages in UTI murine model of and . Immunocompetent and immunocompromised mice with adjusted urine pH were inoculated with and strains, and the efficacy was assessed based on the bacterial concentrations in tissues and fluids at 72 h, with respect to untreated controls.

Identification of host endotypes using peripheral blood transcriptomics in a prospective cohort of patients with endocarditis.

Objectives: Host responses to infection are a major determinant of outcome. However, the existence of different response profiles in patients with endocarditis has not been addressed. Our objective was to apply transcriptomics to identify endotypes in patients with infective endocarditis.

COVID-19 in patients with haematologic malignancies: Effect of RNAemia on clinical outcome in vaccinated patients.

Objectives: Patients with haematologic malignancies (HM) COVID-19 have more severe disease, with increased risk of mortality. Therefore, this study aimed to evaluate the effect of SARS-CoV-2 RNAemia and the specific humoral immune responses on the clinical outcomes of patients with HM and COVID-19.

Methods: Interferon-α/γ (IFN-α/IFN-γ) serum levels, neutralizing antibodies and RNAemia at COVID-19 diagnosis, and persistent RNAemia during the follow-up were evaluated.

Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents.

Despite the increasingly widespread clinical impact of adenovirus (HAdV) infections in healthy individuals and the associated high morbidity in immunosuppressed patients, particularly among the paediatric population, a specific treatment for this virus has yet to be developed. In this study, we report the anti-HAdV activity of sub-micromolar concentrations of four heteroleptic (C^S)-cycloaurated complexes bearing a single thiophosphinamide [, , and ] or thiophosphonamide [] chelating ligand and a dithiocarbamate moiety. In addition to their low cytotoxicity, the findings of mechanistic assays revealed that these molecules have antiviral activity by targeting stages of the viral replication cycle subsequent to DNA replication.

Antiviral activity of immunosuppressors alone and in combination against human adenovirus and cytomegalovirus.

Human adenovirus (HAdV) and cytomegalovirus (HCMV) cause high morbidity and mortality in patients undergoing solid organ transplantation (SOT) and haematopoietic stem cell transplantation (HSCT). Immunosuppressors are used universally to prevent graft-vs-host disease in HSCT and graft rejection in SOT. The long-term use of these drugs is associated with a high risk of infection, but there is also evidence of their specific interference with viral infection.

Acidic Urine pH and Clinical Outcome of Lower Urinary Tract Infection in Kidney Transplant Recipients Treated with Ciprofloxacin and Fosfomycin.

Different factors, including antimicrobial resistance, may diminish the effectiveness of antibiotic therapy, challenging the management of post-transplant urinary tract infection (UTI). The association of acidic urine pH with microbiological and clinical outcomes was evaluated after fosfomycin or ciprofloxacin therapy in 184 kidney transplant recipients (KTRs) with UTI episodes by (N = 115) and (N = 69). Initial urine pH, antimicrobial therapy, and clinical and microbiological outcomes, and one- and six-month follow-up were assessed.

In Vitro and In Vivo Virulence Study of Isolated from the Andalusian Outbreak in 2019.

In 2019, the biggest listeriosis outbreak by (Lm) in the South of Spain was reported, resulting in the death of three patients from 207 confirmed cases. One strain, belonging to clonal complex 388 (Lm CC388), has been isolated. We aimed to determine the Lm CC388 virulence in comparison with other highly virulent clones such as Lm CC1 and Lm CC4, in vitro and in vivo.

IgM-enriched immunoglobulin improves colistin efficacy in a pneumonia model by .

We evaluated the efficacy of ceftazidime or colistin in combination with polyclonal IgM-enriched immunoglobulin (IgM-IG), in an experimental pneumonia model (C57BL/6J male mice) using two multidrug-resistant strains, both ceftazidime-susceptible and one colistin-resistant. Pharmacodynamically optimised antimicrobials were administered for 72 h, and intravenous IgM-IG was given as a single dose. Bacterial tissues count and the mortality were analysed.

Design, synthesis and in vitro biological evaluation of a novel class of anti-adenovirus agents based on 3-amino-1,2-propanediol.

Nowadays there is not an effective drug for the treatment of infections caused by human adenovirus (HAdV) which supposes a clinical challenge, especially for paediatric and immunosuppressed patients. Here, we describe the design, synthesis and biological evaluation as anti-adenovirus agents of a new library (57 compounds) of diester, monoester and triazole derivatives based on 3-amino-1,2-propanediol skeleton. Seven compounds (17, 20, 26, 34, 44, 60 and 66) were selected based on their high anti-HAdV activity at low micromolar concentration (IC from 2.

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome.

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient's hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log copies/mL.

Discovery of a Small Molecule Inhibitor of Human Adenovirus Capable of Preventing Escape from the Endosome.

Human adenoviruses (HAdVs) display a wide range of tissue tropism and can cause an array of symptoms from mild respiratory illnesses to disseminated and life-threatening infections in immunocompromised individuals. However, no antiviral drug has been approved specifically for the treatment of HAdV infections. Herein, we report our continued efforts to optimize salicylamide derivatives and discover compound (JMX0493) as a potent inhibitor of HAdV infection.

Discovery of Novel Substituted -(4-Amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide Analogues as Potent Human Adenovirus Inhibitors.

An effective therapy for human adenovirus (HAdV) infections in immunocompromised patients and healthy individuals with community-acquired pneumonia remains an unmet medical need. We herein reported a series of novel substituted -(4-amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide analogues as potent HAdV inhibitors. Compounds , , , , , , , and exhibited increased selectivity indexes (SI > 100) compared to the lead compound niclosamide, while maintaining sub-micromolar to low micromolar potency against HAdV.

Serinol-Based Benzoic Acid Esters as New Scaffolds for the Development of Adenovirus Infection Inhibitors: Design, Synthesis, and Biological Evaluation.

Over the years, human adenovirus (HAdV) has progressively been recognized as a significant viral pathogen. Traditionally associated with self-limited respiratory, gastrointestinal, and conjunctival infections, mainly in immunocompromised patients, HAdV is currently considered to be a pathogen presenting significant morbidity and mortality in both immunosuppressed and otherwise healthy individuals. Currently available therapeutic options are limited because of their lack of effectivity and related side effects.

Exploration of piperazine-derived thioureas as antibacterial and anti-inflammatory agents. In vitro evaluation against clinical isolates of colistin-resistant Acinetobacter baumannii.

A. baumannii is one of the most important multidrug-resistant microorganisms in hospital units. It is resistant to many classes of antibiotics and the development of new therapeutic strategies is necessary.

Phenotypic changes associated with Colistin resistance due to Lipopolysaccharide loss in Acinetobacter baumannii.

Acinetobacter baumannii can acquire resistance to colistin via complete loss of lipopolysaccharide (LPS) biosynthesis due to mutations in the lpxA, lpxC and lpxD genes. However, although colistin is increasingly being used for the treatment of multidrug resistant infections, very few A. baumannii clinical isolates develop colistin resistance through loss of LPS biosynthesis.

Vaccines for Antibiotic-Resistant Bacteria: Possibility or Pipe Dream?

The increasing incidence of infections caused by antibiotic-resistant bacteria from multiple species, together with the paucity of new antibiotics in the development pipeline, indicates that vaccines could play a role in combating these infections. The development of vaccines for these infections presents unique challenges related to target population selection, vaccine administration, and antigen identification. Advances in genomic, transcriptomic, and proteomic technologies offer great potential for identifying promising antigens that are highly conserved and expressed during human infections.

Lipopolysaccharide loss produces partial colistin dependence and collateral sensitivity to azithromycin, rifampicin and vancomycin in Acinetobacter baumannii.

Treatment options for multidrug-resistant (MDR) strains of Acinetobacter baumannii that acquire resistance to colistin are limited. Acinetobacter baumannii can become highly resistant to colistin through complete loss of lipopolysaccharide (LPS) owing to mutations in the genes encoding the first three enzymes involved in lipid A biosynthesis (lpxA, lpxC and lpxD). The objective of this study was to characterise the susceptibility to 15 clinically relevant antibiotics and 6 antimicrobial peptides (AMPs) of MDR A.