This study aims to analyze the risk factors for the development of multidrug-resistant (MDR) and carbapenem-resistant (CR) bacteria bloodstream infection (BSI) in a patient with acute leukemia (AL) and the mortality in gram-negative bacteria (GNB) BSI. This is a retrospective study conducted at West China Hospital of Sichuan University, which included patients diagnosed with AL and concomitant GNB BSI from 2016 to 2021. A total of 206 patients with GNB BSI in AL were included. The 30-day mortality rate for all patients was 26.2%, with rates of 25.8% for those with MDR GNB BSI and 59.1% for those with CR GNB BSI. Univariate and multivariate analyses revealed that exposure to quinolones (Odds ratio (OR) = 3.111, 95% confidence interval (95%CI): 1.623-5.964, p = 0.001) within the preceding 30 days was an independent risk factor for MDR GNB BSI, while placement of urinary catheter (OR = 6.311, 95%CI: 2.478-16.073, p < 0.001) and exposure to cephalosporins (OR = 2.340, 95%CI: 1.090-5.025, p = 0.029) and carbapenems (OR = 2.558, 95%CI: 1.190-5.497, p = 0.016) within the preceding 30 days were independently associated with CR GNB BSI. Additionally, CR GNB BSI (OR = 2.960, 95% CI: 1.016-8.624, p = 0.047), relapsed/refractory AL (OR = 3.035, 95% CI: 1.265-7.354, p = 0.013), septic shock (OR = 5.108, 95% CI: 1.794-14.547, p = 0.002), platelets < 30 × 109/L before BSI (OR = 7.785, 95% CI: 2.055-29.492, p = 0.003), and inappropriate empiric antibiotic therapy (OR = 3.140, 95% CI: 1.171-8.417, p = 0.023) were independent risk factors for 30-day mortality in AL patients with GNB BSI. Prior antibiotic exposure was a significant factor in the occurrence of MDR GNB BSI and CR GNB BSI. CR GNB BSI increased the risk of mortality in AL patients with GNB BSI.

The current study evaluates the antibacterial activity of Camponotus compressus (Hymenoptera: Formicidae) body crude extracts. The increasing antibiotic resistance of bacteria has prompted the world to turn its attention towards insects in the search for new sources of antibacterial compounds. The body crude extract obtained with different solvents were tested against both Gram positive (Staphylococcus aureus, Bacillus subtilis) and Gram negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae). Standard disc diffusion method was used to perform the activity. The extracts of C. compressus were investigated for their effectiveness against all resistant pathogenic bacteria. Staphylococcus aureus was found to be the most susceptible, exhibiting a high average growth inhibition, while Bacillus subtilis showed a lower average growth inhibition zone. Our findings regarding the inhibitory effect of C. compressus extracts show the presence of a broad-spectrum antibacterial compound. This will be helpful in the search for novel natural antibiotics against robust pathogenic bacterial strains.

Colistin is a polymyxin antimicrobic mainly used to treat infection caused by multi-drug resistant Gram-negative bacteria. Mechanisms of colistin resistance are linked to the mobile colistin resistance (mcr) genes, which are transferable within mobile plasmids. Currently, there is limited research on the environmental dissemination of these genes. The behavioural and morphological characteristics of Apis mellifera L. make honey bees effective environmental bioindicators for assessing the prevalence of antimicrobial-resistant bacteria. This study aims to evaluate the colistin phenotypic and genotypic resistance in environmental Gram-negative bacteria isolated from foraging honey bees, across a network of 33 colonies distributed across the Emilia-Romagna region in Italy. Phenotypic resistances were determined through a microdilution assay using the minimum inhibitory concentration (MIC) with dilutions ranging from 0.5 μg/ml to 256 μg/ml. Strains with MIC values gather than 2 μg/ml were classified as resistant. Also, the identification of the nine mcr genes was carried out using two separate multiplex PCR assays. The study found that 68.5% of isolates were resistant and the genus with the higher resistance rates observed in Enterobacter spp. (84.5%). At least one mcr gene was found in 137 strains (53.3%). The most detected gene was mcr5 (35.3%), which was the most frequently detected gene in the seven provinces, while the least observed was mcr4 (4.8%), detected only in two provinces. These results suggested the feasibility of detecting specific colistin resistance genes in environmentally spread bacteria and understanding their distribution at the environmental level, despite their restricted clinical use. In a One-Health approach, this capability enables valuable environmental monitoring, considering the significant role of colistin in the context of public health.

This study addresses the need for enhanced antimicrobial properties of electrospun membranes, either through surface modifications or the incorporation of antimicrobial agents, which are crucial for improved clinical outcomes. In this context, chitosan-a biopolymer lauded for its biocompatibility and extracellular matrix-mimicking properties-emerges as an excellent candidate for tissue regeneration. However, fabricating chitosan nanofibers via electrospinning often challenges the preservation of their structural integrity. This research innovatively develops a chitosan/polycaprolactone (CH/PCL) composite nanofibrous membrane by employing a layer-by-layer electrospinning technique, enhanced with silver nanoparticles (AgNPs) synthesized through a wet chemical process. The antibacterial efficacy, adhesive properties, and cytotoxicity of electrospun chitosan membranes were evaluated, while also analyzing their hydrophilicity and nanofibrous structure using SEM. The resulting CH/PCL-AgNPs composite membranes retain a porous framework, achieve balanced hydrophilicity, display commendable biocompatibility, and exert broad-spectrum antibacterial activity against both Gram-negative and Gram-positive bacteria, with their efficacy correlating to the AgNP concentration. Furthermore, our data suggest that the antimicrobial efficiency of these membranes is influenced by the timed release of silver ions during the incubation period. Membranes incorporated starting with AgNPs at a concentration of 50 µg/mL effectively suppressed the growth of both microorganisms during the early stages up to 8 h of incubation. These insights underscore the potential of the developed electrospun composite membranes, with their superior antibacterial qualities, to serve as innovative solutions in the field of tissue engineering.

Antimicrobial resistance (AMR) is an increasingly concerning phenomenon that requires urgent attention because it poses a threat to human and animal health. Bacteria undergo continuous evolution, acquiring novel resistance mechanisms in addition to their intrinsic ones. Multidrug-resistant and extensively drug-resistant bacterial strains are rapidly emerging, and it is expected that bacterial AMR will claim the lives of 10 million people annually by 2050. Consequently, the urgent need for the development of new therapeutic agents with new modes of action is evident. The antibacterial prodrug approach, a strategy that includes drug repurposing and derivatization, integration of nanotechnology, and exploration of natural products, is highlighted in this review. Thus, this publication aims at compiling the most pertinent research in the field, spanning from 2021 to 2023, offering the reader a comprehensive insight into the AMR phenomenon and new strategies to overcome it.

The issue of bacterial infections in COVID-19 patients has received increasing attention. Scant data are available on the impact of bacterial superinfection and antibiotic administration on the outcome of hospitalized COVID-19 patients. We conducted a literature review from 1 January 2022 to 31 March 2024 to assess the current burden of bacterial infection and the evidence for antibiotic use in hospitalized COVID-19 patients. Published articles providing data on antibiotic use in COVID-19 patients were identified through computerized literature searches with the search terms [(antibiotic) AND (COVID-19)] or [(antibiotic treatment) AND (COVID-19)]. PubMed and SCOPUS databases were searched from 1 January 2022 to 31 March 2024. No attempt was made to obtain information about unpublished studies. English language restriction was applied. The quality of the included studies was evaluated by the tool recommended by the Joanna Briggs Institute. Both quantitative and qualitative information were summarized by means of textual descriptions. Five hundred fifty-one studies were identified, and twenty-nine studies were included in this systematic review. Of the 29 included studies, 18 studies were on the prevalence of bacterial infection and antibiotic use in hospitalized COVID-19 patients; 4 studies reported on the efficacy of early antibiotic use in COVID-19; 4 studies were on the use of sepsis biomarkers to improve antibiotic use; 3 studies were on the efficacy of antimicrobial stewardship programs and predictive models among COVID-19-hospitalized patients. The quality of included studies was high in 35% and medium in 62%. High rates of hospital-acquired infections were reported among COVID-19 patients, ranging between 7.5 and 37.7%. A high antibiotic resistance rate was reported among COVID-19 patients developing hospital-acquired infections, with a high in-hospital mortality rate. The studies evaluating multi-faceted antimicrobial stewardship interventions reported efficacy in decreasing antibiotic consumption and lower in-hospital mortality.

The rise of multi-drug-resistant (MDR) pathogenic bacteria presents a grave challenge to global public health, with antimicrobial resistance ranking as the third leading cause of mortality worldwide. Understanding the mechanisms underlying antibiotic resistance is crucial for developing effective treatments. Efflux pumps, particularly those of the resistance-nodulation-cell division (RND) superfamily, play a significant role in expelling molecules from bacterial cells, contributing to the emergence of multi-drug resistance. These are transmembrane transporters naturally produced by Gram-negative bacteria. This review provides comprehensive insights into the modulation of RND efflux pump expression in bacterial pathogens by numerous and common molecules (bile, biocides, pharmaceuticals, additives, plant extracts, etc.). The interplay between these molecules and efflux pump regulators underscores the complexity of antibiotic resistance mechanisms. The clinical implications of efflux pump induction by non-antibiotic compounds highlight the challenges posed to public health and the urgent need for further investigation. By addressing antibiotic resistance from multiple angles, we can mitigate its impact and preserve the efficacy of antimicrobial therapies.

Leucine residues are commonly found in the hydrophobic face of antimicrobial peptides (AMPs) and are crucial for membrane permeabilization, leading to the cell death of invading pathogens. Melittin, which contains four leucine residues, demonstrates broad-spectrum antimicrobial properties but also significant cytotoxicity against mammalian cells. To enhance the cell selectivity of melittin, this study synthesized five analogs by replacing leucine with its structural isomer, 6-aminohexanoic acid. Among these analogs, Mel-LX3 exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria. Importantly, Mel-LX3 displayed significantly reduced hemolytic and cytotoxic effects compared to melittin. Mechanistic studies, including membrane depolarization, SYTOX green uptake, FACScan analysis, and inner/outer membrane permeation assays, demonstrated that Mel-LX3 effectively permeabilized bacterial membranes similar to melittin. Notably, Mel-LX3 showed robust antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MDRPA). Furthermore, Mel-LX3 effectively inhibited biofilm formation and eradicated existing biofilms of MDRPA. With its improved selective antimicrobial and antibiofilm activities, Mel-LX3 emerges as a promising candidate for the development of novel antimicrobial agents. We propose that the substitution of leucine with 6-aminohexanoic acid in AMPs represents a significant strategy for combating resistant bacteria.

I. paraguariensis St. Hil. is a south American species of agronomic interest with studies supporting its medicinal properties. As the investigation of active ingredients with antimicrobial effect from medicinal plants is a suitable approach to the current antibacterial resistance problem, the aim of the present study was to determine the antibacterial activity of yerba mate ethanolic extracts against carbapenemase-producing gram-negative bacteria (reference strains and clinical isolates). Extracts showed antibacterial activity against Klebsiella pneumoniae ATCC® BAA-2342™ (KPC producing), Providencia rettgeri (NDM producing), Pseudomonas aeruginosa (MBL producing) and P. aeruginosa (VIM producing) at the concentrations tested. The Minimal-Inhibitory-Concentration and Minimal-Bactericidal-Concentration values ranged between 1 and 32 mg.ml-1 for the reference strains, and between 0.125 and 1 mg.ml-1 for the clinical isolates. The MBC/MIC index characterized the extracts as bactericidal. The combinations of commercial antibiotics and extracts showed a synergistic action on the reference strains studied. The lethal concentration 50 obtained using the Artemia salina toxicity assay were higher than 1 mg.ml-1 for all the extracts, indicating a low toxicity. The in vitro activity and low toxicity suggest that ethanolic I. paraguariensis leaf extracts constitute an outstanding source for new antibacterial compounds, and further studies should be carried out to understand their mechanism of action.

Extensively drug-resistant Pseudomonas aeruginosa infections are emerging as a significant threat associated with adverse patient outcomes. Due to this organism\'s inherent properties of developing antibiotic resistance, we sought to investigate alternative strategies such as identifying \"high value\" antigens for immunotherapy-based purposes. Through extensive database mining, we discovered that numerous Gram-negative bacterial (GNB) genomes, many of which are known multidrug-resistant (MDR) pathogens, including P. aeruginosa, horizontally acquired the evolutionarily conserved gene encoding Zonula occludens toxin (Zot) with a substantial degree of homology. The toxin\'s genomic footprint among so many different GNB stresses its evolutionary importance. By employing in silico techniques such as proteomic-based phylogenetic tracing, in conjunction with comparative structural modeling, we discovered a highly conserved intermembrane associated stretch of 70 amino acids shared among all the GNB strains analyzed. The characterization of our newly identified antigen reveals it to be a \"high value\" vaccine candidate specific for P. aeruginosa. This newly identified antigen harbors multiple non-overlapping B- and T-cell epitopes exhibiting very high binding affinities and can adopt identical tertiary structures among the least genetically homologous P. aeruginosa strains. Taken together, using proteomic-driven reverse vaccinology techniques, we identified multiple \"high value\" vaccine candidates capable of eliciting a polarized immune response against all the P. aeruginosa genetic variants tested.