The isolation of soil microorganisms with the ability to produce antibiotics and other bioproducts represents a key approach for harnessing microbial diversity and discovering biologically significant compounds. Filamentous fungi, which are commonly found in soil, produce substances and compounds rich in biomolecules that function as reducing and stabilizing agents in the synthesis of inorganic nanoparticles (NPs) such as gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs). These nanoparticles play a crucial role in enhancing the efficacy of antibiotics by improving drug delivery, increasing bacterial targeting, and combating resistance mechanisms.

This study investigates the efficacy of filamentous fungi isolated from soil samples in producing antimicrobial compounds, as well as their ability to synthesise AuNPs and AgNPs, with the aim of developing new next-generation antibiotics. The isolated fungi were tested for antimicrobial activity using the agar-well diffusion method against pathogenic bacterial strains. The fungi showing the most promising antimicrobial results were identified through DNA sequencing, and their capability to synthesize NPs was explored by exposing the extracellular extract to chloroauric acid or silver nitrate.

The results demonstrated promising minimum inhibitory concentration (MIC) values against pathogenic bacteria, including Escherichia coli, Staphylococcus aureus, Bacillus cereus, and Pseudomonas aeruginosa. The follow-up work involves the characterization of antimicrobial compounds and NPs, along with further optimization of their use.

This study underscores the importance of exploiting fungi isolated from soil to discover novel antimicrobials and highlights the advancement of green nanoparticle synthesis as crucial for creating next-generation antibiotics. This approach aims to minimize ecological harm while addressing antibiotic resistance.

Introduction: Streptococcus pneumoniae is an important human pathogen responsible for both localized infections and invasive pneumococcal disease (IPD). Of particular concern is the increasing resistance to penicillin, the antibiotic of choice for the treatment of pneumococcal infections. As antimicrobial susceptibility varies by geographic location and the site of infection, the treatment guidelines must be derived from the local epidemiology.

Methods: Surveillance was conducted at the Department of Clinical Microbiology, the Clinical Hospital Center Rijeka, in the period of January 2020 to December 2024. Invasive isolates were defined as strains collected from normally sterile sites (blood, pleural fluid, cerebrospinal fluid). The total number of pneumococcal isolates collected from inpatients and outpatients from Primorje-Gorski Kotar County, Croatia, was 925, of which 156 were invasive strains. All strains were tested for their antimicrobial susceptibility, with a focus on penicillin resistance.

Results: The number of invasive isolates was twice as high in the period from 2022 to 2024 than that in the previous two years. More than 50% of invasive strains were isolated from adults over 65 years of age. The resurgence of pneumococcal infections can be explained by the gradual withdrawal of anti-COVID pandemic measures. A large number of all isolates showed a reduced susceptibility to penicillin, with significant differences between invasive and non-invasive strains (28% reduced susceptibility in invasive and 49% in non-invasive strains).

Conclusions: The increasing trend of decreased susceptibility to penicillin observed in non-invasive pneumococcal strains is of great concern, as these strains, which have successfully spread in the population, are an important source of invasive infections and a reservoir of antimicrobial resistance. Rising penicillin resistance rates are affecting the treatment of IPD, especially pneumococcal meningitis. Nevertheless, parenteral penicillin is still the drug of choice for the treatment of pneumococcal pneumonia in Croatia.

The antibiotic resistance crisis has led the WHO to name several pathogens as priorities for the development of new treatments. In this context, a promising alternative approach to conventional antibiotics (ATBs) has been explored to fight multi-drug-resistant bacteria. The so-called “anti-virulence strategy” aims at diminishing bacterial pathogenicity without affecting cell growth, in order to circumvent the selection pressure issues mediated by standardantibiotherapy. Anti-virulence agents (AVAs) could find a use in biotherapy to restore the efficacy of ATBs, or in monotherapy to potentiate the immune system’s response. Among the WHO’s targets stands the opportunistic gram-negative bacterium Pseudomonas aeruginosa, the main cause of chronic and hard-to-treat lung infections in immunocompromised patients. A major virulence trait of P. aeruginosa is the development of biofilms, i.e., microcolonies embedded in a protective self-produced extracellular matrix. These complex structures provide advantageous microenvironments for pseudomonal growth, as well as shielding barriers against the immune system and ATBs. The development of biofilms is mostly coordinated by quorum sensing (QS), a bacterial communication network regulating pathogenicity according to population density. Therefore, the development of quorum sensing inhibitors (QSIs) has been considered a good strategy to eradicate P. aeruginosa infections. In the literature, several bi-aromatic hybrids have been described as potent QSIs against P. aeruginosa. By structural analogy, the AGIR laboratory highlighted a first-hit 2-indazolyl-4-quinolone with promising anti-virulence properties. More recently, the team developed a new family of aminoquinoline bi-aromatic hybrids as QSIs able to efficiently inhibit P. aeruginosa motility and biofilm formation. This presentation describes the synthesis of those new AVAs as well as their physicochemical and biological evaluation.

The increasing demand for natural cosmetic products is indicative of a growing awareness of the potential adverse environmental and health implications associated with synthetic compounds. Synthetic preservatives, which are commonly employed in cosmetics to prevent microbial contamination, have been implicated in the occurrence of allergic reactions and contribute to environmental pollution. This has led to a growing demand for safer and more sustainable alternatives. Natural preservatives, particularly bioactive compounds derived from microorganisms, have emerged as a promising substitute due to their biodegradability and compatibility with consumer safety standards.

Of particular interest are bioactive metabolites produced by yeasts, which have gained attention for their ability to inhibit the growth of pathogenic microorganisms.

This study investigated the antimicrobial potential of peptides produced by the yeasts Saccharomyces cerevisiae and Wickerhamomyces anomalus as natural preservatives in a cosmetic emulsion formulation. Antimicrobial efficacy was evaluated using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and a 48-hour challenge test against common pathogenic microorganisms including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Candida albicans. The results showed that the 2-10 kDa peptidic fraction derived from S. cerevisiae metabolism achieved MICs as low as 450 µg/mL for E. coli and 56.25 µg/mL for S. aureus. Similarly, metabolites from W. anomalus exhibited MICs of 450 µg/mL against E. coli and 575 µg/mL against S. epidermidis. The 48-hour challenge test showed a significant reduction in microbial growth when the peptide fractions were applied, particularly against E. coli and S. aureus.

This study highlights the potential of yeast-derived bioactive metabolites as sustainable and effective alternatives to synthetic preservatives in cosmetics.

Introduction: Cefiderocol, a siderophore cephalosporin, has emerged as a key treatment for managing multidrug-resistant (MDR) infections, with its time-dependent pharmacodynamics optimized by prolonged infusion to maintain effective concentrations (fT>MIC). While current technical data sheets recommend reconstitution and use within 6 hours, due to limited stability data, recent findings suggest cefiderocol concentrations remain stable for up to 72 hours at 25°C in elastomeric pumps. Despite its potential, the application in 24-hour continuous infusions (CIs) in an outpatient parenteral antibiotic therapy (OPAT) setting remains undocumented. This case highlights the successful use of cefiderocol via 24-hour CI in an elastomeric pump, supported by therapeutic drug monitoring (TDM), achieving effective serum levels in an OPAT setting.

Methods: A 31-year-old virologically suppressed male, with a prior history of AIDS (cryptococcal meningitis) in 2023, presented with right-sided otomastoiditis caused by Klebsiella pneumoniae producing New Delhi metallo-beta-lactamase (NDM). Given the resistance profile and the need for prolonged therapy, cefiderocol was initiated at 6 g/day via a 24-hour CI using an elastomeric pump (Baxter Infusor LV 10 mL/h). TDM was performed on days 17 and 45 to assess plasma concentrations and ensure pharmacokinetic/pharmacodynamic (PK/PD) target attainment.

Results: TDM confirmed steady-state concentrations (Css 25.2–28.1 mg/L), achieving optimal PK/PD target attainment, such as 100%t>4-6 MIC (fCss/MIC 11.8–12.1). Significant clinical improvement avoided the need for planned surgery, with no adverse events reported from the venous catheter, antibiotic therapy, or elastomeric pump.

Conclusions: This approach underscores the feasibility and efficacy of cefiderocol administered by 24 h CI using elastomeric pumps, supported by real-time TDM to achieve an aggressive PK/PD target for the treatment of otomastoiditis due to NDM-producing Klebsiella pneumoniae. By minimizing hospitalization and enabling outpatient care, this strategy also significantly enhances the patient’s quality of life.

Introduction: Though antibiogram generated through disc diffusion assay is a widely used method to assist the clinician in selecting appropriate antibiotics for patient treatment, correlation of in vitro efficacy of antibiotics with their in vivo efficacy needs deeper investigations.

Methods: The model host Caenorhabditis elegans was challenged with three different antibiotic-resistant gram-negative bacterial pathogens (Pseudomonas aeruginosa, Vibrio cholerae, or Escherichia coli) in absence or presence of the MIC-­­levels of those antibiotics belonging to different classes, to whom these pathogens were shown to be sensitive in disc diffusion assay. Worm survival was quantified over a period of five days through microscopic live-dead count.

Results: While ampicillin, ciprofloxacin, and tetracycline could offer significant protection to the worm population in face of V. cholerae challenge, streptomycin and clindamycin failed to do so. Streptomycin also could not rescue worms against E. coli. As ampicillin and ciprofloxacin were effective against E. coli too, antibiotic-response of both these pathogens in worm model can be said to have some commonality. While ciprofloxacin, a fluroquinolone antibiotic effective against remaining two pathogens, could not protect the worm population from P. aeruginosa attack, another quinolone antibiotic ofloxacin could do this. Cefotaxime, a third-generation cephalosporin also failed to confer any protection on worm population challenged with P. aeruginosa. The correlation between ‘MIC’ and ‘in vivo efficacy (as per first-day endpoint)’ was stronger in case of E. coli (r: -0.97) than P. aeruginosa (r: -0.53). In case of V. cholerae (r: 0.23), antibiotics with lower MIC exhibited lesser in vivo efficacy than those with higher MIC. Correlation between ‘diameter of zone of inhibition’ and ‘in vivo efficacy (as per first-day endpoint)’ was found to be better for V. cholerae (r:0.62) than remaining two pathogens.

Conclusions: Further investigation with a broader range of antibiotics and pathogens should be conducted to check whether in vivo assays with simple model hosts can be a better predictor of clinical efficacy of antibiotics, than the conventional disc diffusion or broth dilution assays.

Imine pharmacophore groups offer the advantage of serving as the foundation for various drug representatives. Examples include furazolidone for bacterial or protozoal diarrhea, nitrofurantoin for uncomplicated urinary tract infections, and imbruvica for chronic lymphocytic leukemia and mantle cell lymphoma. Cinnamaldehyde, a major constituent of cinnamon oil, is an aromatic compound with a benzene ring and an aldehyde group attached to an unsaturated C=C bond at both ends. Studies on cinnamaldehyde have shown that it exhibits a broad range of biological activities. A novel imine compound, created using trans-cinnamaldehyde and polyamines such as tris (2-aminoethyl) amine (compound 5), was synthesized. The antibacterial activity of the compound was tested against clinical isolates (S. aureus, S. aureus ATCC 6538, S. aureus ATCC 25923, S. aureus UAMS-1, and S. aureus UAMS -929) using the two-fold microdilution method. The obtained results were compared with the results of the ampicillin and gentamicin. It was revealed that the MIC of F2-112B in the case of S. aureus (8 μg/mL) were lower than the MIC of ampicillin (16 μg/mL). The MIC value of compound F2-112B was equal (16 μg/ml) to ampicillin in the case of S. aureus ATCC 6538. According to the results, compared with other strains, compound 5 showed similar activities against UAMS-929 and ATCC 25923, and its MIC values were 64 µg/ml for each strain. The MIC value was 128 µg/ml when compound 5 was tested against the S. aureus strain UAMS-1. We also examined the potential binding mode between compound 5 and bacterially derived target proteins and carried out a protein–ligand docking simulation. The docking results for PBP2a (5M18) indicated that compound 5 successfully binds to the allosteric binding site of the protein, which aligns with the binding site of Cefepime, demonstrating a high binding affinity of -8.42 Kcal/mol.

Antimicrobial resistance poses a critical challenge to global public health, complicating the treatment of common and life-threatening infections caused by bacteria, viruses, fungi, and parasites. This issue is particularly severe in developing regions, where factors such as the inappropriate use of antibiotics and inequalities in healthcare access contribute to the rise of multidrug-resistant strains. Unfortunately, Colombia is no exception to this growing problem. Nationally, hospital-associated infections caused by Klebsiella pneumoniae and Pseudomonas aeruginosa have become increasingly frequent, with resistance to broad-spectrum antimicrobials such as carbapenems being on the rise. Additionally, a descriptive analysis of bacterial isolates from intensive care units (ICUs) across twenty hospitals in twelve Colombian cities from 2019 to 2021 revealed a significant increase in the prevalence of multidrug-resistant microorganisms. In the most recent report (2019) on laboratory surveillance of antimicrobial resistance in healthcare-associated infections (HAIs) by the National Institute of Health (INS) of Colombia, the department of Magdalena exceeded national resistance rates for Escherichia coli, K. pneumoniae, P. aeruginosa (resistant to at least one carbapenem), and Staphylococcus aureus (oxacillin-resistant). However, no updated epidemiological data on antibacterial resistance in this region are currently available. This study presents an epidemiological analysis of the resistance profiles of pathogenic bacterial strains in the department of Magdalena, Colombia, during 2023–2024. A retrospective descriptive study was conducted using data from the Julio Méndez Barreneche University Hospital (HUJMB) in Santa Marta D.T.C.H. The findings allow us to identify the most prevalent Gram-positive and Gram-negative bacterial strains in the region and explore potential risk factors.

Antibiotic resistance in bears, while not as widely studied as in humans or livestock, has received increasing attention in recent years. This phenomenon primarily arises from human activities introducing antibiotic-resistant bacteria into wild ecosystems, where animals such as bears can be exposed. Due to habitat destruction and a lack of available food, it is very common for bears to rummage through landfills, where they might ingest bacteria that have developed resistance from exposure to antibiotics that are used in human medicine or agriculture. Another source of contamination is when water systems are contaminated, through which these bacteria can spread into natural habitats. The objective of this review is to describe the presence of antibiotic-resistant bacteria in bear species, their sources and their possible impact on the population. Concerning the available data, it is possible to observe that existing studies have focused on Sloth bears (Melursus ursinus), black bears (Ursus americanus), giant panda (Ailuropoda melanoleuca), polar bear (Ursus maritimus) and brown bear (Ursus arctos). The most observed species of bacteria were Escherichia coli. While the direct impact of antibiotic resistance on bear populations is still unclear, the presence of resistant bacteria in wild bears is concerning. It could make them more susceptible to infections that are difficult to treat, potentially affecting their overall health and survival. Antibiotic resistance in bears is an emerging area of study that highlights the far-reaching consequences of antibiotic overuse in humans and livestock. It illustrates how environmental contamination can spread resistance even to remote wildlife populations, underscoring the need for responsible antibiotic use and better waste management to limit this global problem.

Introduction: Bloodstream infection (BSI) is critical medical emergency associated with a high mortality rate. Rapid and accurate identification of the infectious agent and antimicrobial susceptibility is critical to initiating the appropriate, targeted therapy and improving patient outcomes. The aim of this study was to evaluate the performance of a Molecular Mouse System (MMS) for the rapid identification of Gram-negative bacteria (GNB) and their resistance genes directly from a positive blood culture (BC). Methods: A total of 80 positive BC samples from different clinical departments with microscopically detected GNB were analyzed using rapid molecular multiplex assays. Results: Compared to the routine culture methods, the MMS achieved a sensitivity and specificity of 98% for GNB detection. Only 2 out of 80 GNB (Pseudomonas putida and Acinetobacter calcoaceticus) were not identified by the MMS, as they were off-panel bacteria, while Enterobacter aerogenes was identified at the genus level (Enterobacteriaceae). However, in 2 out of 80 BC samples, the MMS revealed GNB that were not identified using culture-based methods but were later confirmed using the FILMARRAY^TM multiplex PCR panel. In one polymicrobial sample, the MMS detected multidrug-resistant Stenotrophomonas maltophilia, which was not detected by the routine culture. The type of extended-spectrum beta-lactamase resistance gene (ESẞL) detected using the MMS was mostly CTX-M-1/9 (n=19/20), alone or in combination with SHV-type β-lactamase or/and with one of the three different types of carbapenemase resistance genes (OXA-48, KPC, NDM). Furthermore, the MMS identified the resistance gene for the carbapenemase OXA-23 in an Acinetobacter baumannii-positive BC sample. Conclusion: These results suggest that the MMS is considered an effective and beneficial diagnostic method for faster therapeutic decision-making in patients with BSIs.