One of the burning issues facing healthcare organizations is multidrug-resistant (MDR) bacteria. P. aeruginosa is an MDR opportunistic bacterium responsible for nosocomial and fatal infections in immunosuppressed individuals. According to previous studies, efflux pump activity and biofilm formation are the most common resistance mechanisms in P. aeruginosa. The aim of this study was to propose new antimicrobial peptides (AMPs) that target P. aeruginosa and can effectively address these resistance mechanisms through in silico and in vitro assessments. Since AMPs are an attractive alternative to antibiotics, in vitro experiments were carried out along with bioinformatics analyses on 19 Nef peptides (derived from the HIV-1 Nef protein) in the current study. Several servers, including Dbaasps, Antibp2, CLASSAMP2, ToxinPred, dPABBs and ProtParam were used to predict Nef peptides as AMPs. To evaluate the binding affinities, a molecular docking analysis was performed with the HADDOCK web server for all Nef peptide models against two effective proteins of P. aeruginosa (MexB and PqsR) that play a role in efflux and quorum sensing. Moreover, the antibacterial and antibiofilm activity of the Nef peptides was investigated in a resistant strain of P. aeruginosa. The results of molecular docking revealed that all Nef peptides have a significant binding affinity to the abovementioned proteins. Nef-Peptide-19 has the highest affinity to the active sites of MexB and PqsR with the HADDOCK scores of -136.1 ± 1.7 and -129.4 ± 2, respectively. According to the results of in vitro evaluation, Nef peptide 19 showed remarked activity against P. aeruginosa with minimum inhibitory and bactericidal concen-trations (MIC and MBC) of 10 µM and 20 µM, respectively. In addition, biofilm inhibitory activity was observed at a concentration of 20 µM. Finally, Nef peptide 19 is proposed as a new AMP against P. aeruginosa.

Respiratory tract infections (RTIs) have a significant impact on global health, especially among children and the elderly. The key bacterial pathogens Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Staphylococcus aureus and non-fermenting Gram Negative bacteria such as Acinetobacter baumannii and Pseudomonas aeruginosa are most commonly associated with RTIs. These bacterial pathogens have evolved a diverse array of resistance mechanisms through horizontal gene transfer, often mediated by mobile genetic elements and environmental acquisition. Treatment failures are primarily due to antimicrobial resistance and inadequate bacterial engagement, which necessitates the development of alternative treatment strategies. To overcome this, our review mainly focuses on different virulence mechanisms and their resulting pathogenicity, highlighting different therapeutic interventions to combat resistance. To prevent the antimicrobial resistance crisis, we also focused on leveraging the application of artificial intelligence and machine learning to manage RTIs. Integrative approaches combining mechanistic insights are crucial for addressing the global challenge of antimicrobial resistance in respiratory infections.

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The increasing problem of antibiotic resistance in bacteria leads to an urgent need for new antimicrobial agents. Alternative treatments for bacterial infections need to be explored to tackle this issue. Plant-based substances are emerging as promising options. Manilkara zapota L. contains compounds with antibiotic activities, and anti-inflammatory, antitumor, antipyretic, and antioxidant properties. It has medicinal properties and contains bioactive compounds, like tannins, flavonoids, and triterpenoids. This review aimed to comprehensively evaluate the existing literature on the potential medicinal and therapeutic benefits of M. zapota in bacterial infections by utilizing data from in vivo and in vitro studies. M. zapota has the potential to be a nutritional source of antimicrobial food. Numerous preclinical studies have demonstrated the antibacterial activities of M. zapota and its components. The antibacterial mechanisms of this fruit could interact with bacterial cell structures such as cell walls or membranes.

BACKGROUND: Fever in children represents one of the most common causes of medical evaluation. Infants younger than 90 days of age are at higher risk of severe and invasive bacterial infections (SBI and IBI). However, clinical signs and symptoms of viral and bacterial infections in young infants are frequently similar, and several studies have shown that the risk of SBIs remains non-negligible even in the presence of a positive point-of-care viral test. Our study aims to evaluate whether the proportion of SBIs and IBIs in febrile infants younger than 90 days during the COVID-19 pandemic was higher than that in the pre-pandemic period, and to describe the proportion of SBIs and IBIs in infants with and without SARS-CoV-2 infection.
METHODS: This was a retrospective single-center cohort study conducted at the Children\'s Hospital of the University of Padua in Italy, involving febrile young infants evaluated in the Pediatric Emergency Department (PED) and admitted to Pediatric Acute Care Unit (PACU) between March 2017 to December 2022. Infants admitted before the COVID-19 pandemic were compared to infants admitted during the pandemic period and SARS-CoV-2 positive patients to the negative ones.
RESULTS: 442 febrile infants younger than 90 days were evaluated in Padua PED and admitted to the wards. The proportion of SBIs and IBIS did not significantly change over the study periods, ranging between 10.8% and 32.6% (p = 0.117) and between 0% and 7.6%, respectively (p = 0.367). The proportion of infants with a diagnosis of SBIs and IBIs was higher in the SARS-CoV-2 negative group (30.3% and 8.2%, respectively) compared to the positive group (8.5% and 2.8%, respectively) (p < 0.0001). The most common diagnosis in both groups was UTI, mainly caused by E. coli. A similar proportion of blood and urine cultures were performed, whereas lumbar puncture was more frequently performed in SARS-CoV-2 negative infants (40.2% vs 16.9%, p = 0.001).
CONCLUSIONS: Although the risk of concomitant serious bacterial infection with SARS-CoV-2 is low, it remains non-negligible. Therefore, even in SARS-CoV-2-positive febrile infants, we suggest that the approach to screening for SBIs remains cautious.

The interferon-stimulated gene OAS1 has well-defined antiviral properties. In two recent issues of Immunity, Harioudh et al. describe a non-canonical function of OAS1 that selectively protects the translation of proteins involved in defense against viral or bacterial infections.

OBJECTIVE: Bacterial infections, particularly bacteremia, urinary tract infections (UTIs), and pus infections, remain among hospitals\' most worrying medical problems. This study aimed to explore bacterial diversity, infection dynamics, and antibiotic resistance profiles of bacterial isolates.
METHODS: We analyzed data from 1750 outpatients and 920 inpatients, of whom 1.6% and 8.47% respectively had various bacterial infections.
RESULTS: The analysis revealed that UTIs were the most prevalent at 41.01%, particularly affecting women. UTIs also showed a distinct distribution across admission departments, notably in emergency (23.07%) and pediatric (14.10%) units. The most frequently isolated microorganisms were Escherichia coli (E. coli), followed by Klebsiella ornithinolytica. Skin infections followed UTIs, accounting for 35.88% of cases, more prevalent in men, with Staphylococcus aureus (S. aureus) being the primary pathogen (57%). Gram-negative bacteria (GNB) like E. coli and Pseudomonas aeruginosa contributed significantly to skin infections (43%). Bacteremia cases constituted 11.52% of bacterial infections, predominantly affecting women (67%) and linked to GNB (78%). A comparative study of antibiotic susceptibility profiles revealed more pronounced resistance in GNB strains isolated from inpatients, particularly to antibiotics such as Amoxicillin/clavulanic acid, Tetracyclin, Gentamicin, Chloramphenicol, and Ampicillin. In contrast, strains from ambulatory patients showed greater resistance to Colistin. Gram-positive bacteria from hospitalized patients showed higher resistance to quinolones and cephalosporins, while ambulatory strains showed high resistance to aminoglycosides, macrolides, fluoroquinolones, and penicillin. Furthermore, these analyses identified the most effective antibiotics for the empirical treatment of both community-acquired and nosocomial infections. Ciprofloxacin, aztreonam, and amikacin exhibited low resistance rates among GNB, with gentamicin and chloramphenicol being particularly effective for community-acquired strains. For S. aureus, ciprofloxacin, rifampicin, and cefoxitin were especially effective, with vancomycin showing high efficacy against community-acquired isolates and fosfomycin and chloramphenicol being effective for hospital-acquired strains.
CONCLUSIONS: These results are essential for guiding antibiotic therapy and improving clinical outcomes, thus contributing to precision medicine and antimicrobial stewardship efforts.

BACKGROUND: Data have shown that vitamin B12 has immunomodulatory effects via different pathways, which could influence the pathophysiology of sepsis. The objective of this study was to investigate whether vitamin B12 levels, assessed by the measurement of holotranscobalamin (HTC), total vitamin B12 (B12), and methylmalonic acid (MMA, which accumulates in case of B12 deficiency), are associated with the development of sepsis in patients with onset of bacterial infection.
METHODS: This was a single-center, prospective observational pilot study. Adult patients who presented to the emergency department with bacterial infection confirmed by a positive microbiological culture result were included in the study and followed up for 6 days to assess whether they developed sepsis or not. The primary objective was to compare HTC concentration in patients who developed sepsis to those who did not develop sepsis. Secondary objectives were the evaluation of B12 and MMA concentrations in those two groups. Multiple logistic regression models were used, with presence of sepsis as the outcome variable, and HTC, B12, and MMA concentrations as predictor variables, separately, and adjusted for potential confounders.
RESULTS: From 2019 to 2022, 2131 patients were assessed for eligibility, of whom 100 met the inclusion criteria. One patient was excluded from the analysis due to missing data. Of the 99 patients, 29 developed sepsis. There was no evidence for an association between HTC or B12 concentration and the development of sepsis (OR 0.65, 95% CI 0.31-1.29, p = 0.232, OR 0.84, 95% CI 0.44-1.54, p = 0.584, respectively). There was an association between MMA concentration and the development of sepsis, with a positive effect, i.e. with increasing MMA, the odds for sepsis increased (OR 2.36, 95% CI 1.21-4.87, p = 0.014). This association remained significant when adjusted for confounders (OR 2.72, 95% CI 1.23-6.60, p = 0.018).
CONCLUSIONS: Our study found an association between elevated MMA concentration and the development of sepsis. We did not find an association between HTC and B12 concentrations and the development of sepsis. Further, larger studies are warranted, as it could lead to interventional trials investigating whether B12 supplementation provides a clinical benefit to patients with infection or sepsis.
BACKGROUND: The study was registered on ClinicalTrials.gov under the identifier NCT04008446 on June 17, 2019.

UNASSIGNED: Spontaneous bacterial peritonitis (SBP) represents a critical and potentially lethal condition that typically develops in individuals with liver cirrhosis. This meta-analysis aimed to assess diabetes mellitus (DM) as a risk factor for SBP in liver cirrhotic patients.
UNASSIGNED: Following PRISMA guidelines, fifteen studies were included, for a total of 76 815 patients. The risk of bias was assessed using the Newcastle-Ottawa scale (NOS). We represented the results as risk ratios (RR) with the corresponding 95% confidence intervals (CI) using RevMan software. Additionally, we pooled the hazard ratios (HR) for developing SBP in patients with DM from the included studies.
UNASSIGNED: The meta-analysis shows a significantly increased risk of SBP in cirrhotic patients with DM (HR: 1.26; 95% CI [1.05-1.51], P=.01; HR: 1.70; 95% CI [1.32-2.18], P<.001).
UNASSIGNED: The study signifies that DM is an independent risk factor for SBP, emphasizing the need for targeted preventive measures in this specific population.

Vaccination against bacteria offers its share of challenges, and important progress has been made in recent years. Conventional vaccinology has protected poultry for decades with killed and attenuated bacterial vaccines. Because of the limitations of these vaccines, and given the latest technological advances, other types of vaccines were developed using various strategies. New vaccines are also being commercialized using viral or bacterial recombinant vectors or in the form of subunit vaccines developed by a genomic approach and bioinformatics analyses. As bacteria are forever-evolving microorganisms, there is no doubt that vaccine strategies preventing bacterial diseases will also evolve and that new generations of vaccines are yet to come.
Estudio recapitulativo- Evolución de las vacunas bacterianas: de Pasteur a la genómica. La vacunación contra bacterias ha presentado una serie de desafíos y en los últimos años se han logrado avances importantes. La vacunología convencional ha brindado protección a la avicultura comercial durante décadas con vacunas bacterianas muertas y atenuadas. Debido a las limitaciones de estas vacunas y considerando los últimos avances tecnológicos, se han desarrollado otros tipos de vacunas utilizando diversas estrategias. También se están comercializando nuevas vacunas utilizando vectores recombinantes virales o bacterianos o en forma de vacunas subunitarias desarrolladas mediante un enfoque genómico y por análisis bioinformáticos. Como las bacterias son microorganismos en constante evolución, no hay duda de que las estrategias de vacunación que previenen las enfermedades bacterianas también evolucionarán y que aún están por llegar nuevas generaciones de vacunas.