Search Results (6,503)

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) poses significant challenges in healthcare due to its multidrug resistance and high mortality rates among critically ill patients. Results: We enrolled 45 patients. Cefiderocol was administered to 40% of patients, often (38.8%) in combination with other antibiotics. Colistin was administered to 60% of patients and always in combination, mostly with ampicillin–sulbactam. The overall ECS and OCS rates were 77.8% and 66.7%, respectively. Patients treated with an initial cefiderocol-based regimen showed a higher rate of ECS compared with patients initially treated with colistin-based regimens (100% vs. 63%, p < 0.05). Patients treated with cefiderocol alone showed a higher rate of ECS compared with patients treated with cefiderocol-based regimens (100% vs. 70.6%, p < 0.05). No differences in OCS rates were recorded depending on the treatment received. Additionally, cefiderocol regimens were associated with fewer ADRs compared to colistin-based treatment. Methods: This prospective observational study enrolled patients with CRAB infections from January 2022 to August 2023. Patients were treated with cefiderocol-based or colistin-based regimens and were monitored for 28 days to assess early clinical success (ECS), overall clinical success (OCS) and adverse drug reactions (ADRs). Conclusions: This study highlights the potential advantages of cefiderocol, even used as a monotherapy, in treating CRAB, especially when early clinical and laboratory response was assessed. This research contributes to the ongoing discussion on the most effective and safe treatments for combating CRAB infections, supporting the use of cefiderocol in clinical practice. Full article

In an aquaponic system, fish and plants are cultivated together in a symbiotic environment where they mutually benefit, using significantly less water than traditional farming methods. The main aim of this study was to investigate the occurrence of antimicrobial resistance in two aquaponic systems implemented in two Chilean high schools using rainbow trout and lettuce cultures. When water samples (fish tank, biofilter, and plant raft) were analyzed over a three-month period, no resistance to oxytetracycline was detected, whereas the occurrence of resistance to florfenicol was rather small, ranging from 0.01% to 3.1% of bacterial culturable counts. Eighteen isolates were recovered from various sources as representatives of the florfenicol-resistant population, and all of them belonged to the Pseudomonas genus, showing a multi-drug-resistance phenotype and exhibiting simultaneous resistance to 7–13 antimicrobials. All isolates exhibited resistance to amoxicillin, chloramphenicol, florfenicol, and furazolidone and susceptibility to meropenem, oxytetracycline, oxolinic acid, flumequine, ciprofloxacin, and enrofloxacin. Five and two isolates carried the amphenicol-resistance-encoding genes floR and cmlA, respectively, whereas no carriage of integrons or the fexA, fexB, pexA, optrA, and cfr genes encoding for florfenicol resistance was detected. Eleven isolates carried plasmids, but only two of them were able to transfer their plasmid content by conjugation. The knowledge of the microbiome associated with aquaponic systems is still scarce, and their role as potential reservoirs of antimicrobial-resistant bacteria and related genes of these systems must be elucidated. Full article

Staphylococcus aureus, a prevalent pathogen associated with infectious and foodborne diseases, is also a significant cause of intramammary infections in dairy farms. This study aimed to determine the phenotypic and molecular characterization of S. aureus in two different stock sizes of dairy farms in Henan province (HN) and the Inner Mongolia autonomous region (IM), China, through biofilm formation, antimicrobial resistance, virulence, and molecular type of S. aureus isolates. In HN, 74 S. aureus isolates (60.7%) were recovered from 122 bulk tank milk samples, while in IM, 24 S. aureus isolates (17.4%) were detected from 161 samples soured from various origins. Notably, 25.7% (19/74) of isolates in HN and 20.8% (5/24) in IM exhibited multidrug-resistant (MDR) phenotypes. Molecular typing revealed distinct patterns: ST97 (n = 32) and spa type t189 (n = 20) predominated in HN, whereas ST50 (n = 13) and spa type t518 (n = 11) were prevalent in IM. Additionally, three isolates harbored both tsst-1 and lukF-PV genes, and two MRSA strains displayed a MDR phenotype in raw milk samples from HN. Biofilm formation was observed in 91.8% strains. Phylogenetic analysis identified two subpopulations (lineages 1 and 2). Among them, cluster 6 in lineage 2 comprised S. aureus strains from three sources within a farm, suggesting potential cross contamination during different stages in IM. Remarkably, among 19 MDR isolates in HN, ST398 MSSA strains exhibited a higher multidrug resistance compared to non-ST398 MSSA strains. This study underscores the high prevalence and diverse characteristics of S. aureus in raw milk, necessitating enhanced surveillance and control measures to mitigate associated risk. Full article

The global spread of antimicrobial resistance genes (ARGs) poses a significant threat to public health. While antibiotics effectively treat bacterial infections, they can also induce gut dysbiosis, the severity of which varies depending on the specific antibiotic treatment used. However, it remains unclear how gut dysbiosis affects the mobility and dynamics of ARGs. To address this, mice were pre-treated with streptomycin, ampicillin, or sulfamethazine, and then orally inoculated with Salmonella enterica serovar Typhimurium and S. Heidelberg carrying a multi-drug resistance IncA/C plasmid. The streptomycin pre-treatment caused severe microbiome perturbation, promoting the high-density colonization of S. Heidelberg and S. Typhimurium, and enabling an IncA/C transfer from S. Heidelberg to S. Typhimurium and a commensal Escherichia coli. The ampicillin pre-treatment induced moderate microbiome perturbation, supporting only S. Heidelberg colonization and the IncA/C transfer to commensal E. coli. The sulfamethazine pre-treatment led to mild microbiome perturbation, favoring neither Salmonella spp. colonization nor a conjugative plasmid transfer. The degree of gut dysbiosis also influenced the enrichment or depletion of the ARGs associated with mobile plasmids or core commensal bacteria, respectively. These findings underscore the significance of pre-existing gut dysbiosis induced by various antibiotic treatments on ARG dissemination and may inform prudent antibiotic use practices. Full article

Tuberculosis (TB) represents a global public health threat and is a leading cause of morbidity and mortality worldwide. Effective control of TB is complicated with the emergence of multidrug resistance. Yet, there is a fundamental gap in understanding the complex and dynamic interactions between different Mycobacterium tuberculosis strains and the host. In this pilot study, we investigated the host immune response to different M. tuberculosis strains, including drug-sensitive avirulent or virulent, and rifampin-resistant or isoniazid-resistant virulent strains in human THP-1 cells. We identified major differences in the gene expression profiles in response to infection with these strains. The expression of IDO1 and IL-1β in the infected cells was stronger in all virulent M. tuberculosis strains. The most striking result was the overexpression of many interferon-stimulated genes (ISGs) in cells infected with the isoniazid-resistant strain, compared to the rifampin-resistant and the drug-sensitive strains. Our data indicate that infection with the isoniazid-resistant M. tuberculosis strain preferentially resulted in cGAS-STING/STAT1 activation, which induced a characteristic host immune response. These findings reveal complex gene signatures and a dynamic variation in the immune response to infection by different M. tuberculosis strains. Full article

Ursolic acid (UA) and oleanolic acid (OA) are hydrophobic triterpenoid isomers with demonstrated anti-mycobacterial (Mtb) and immune-regulatory properties, although their poor solubility limits clinical use. We report the development of solid lipid microparticles (SLMs) as delivery vehicles for UA and OA and evaluate their anti-Mtb efficacy in vitro and in vivo, as well as their acute toxicity. SLMs measured 0.7–0.89 µM in size, with complete in vitro release of OA and UA at 40 and 32 h, respectively. The minimum inhibitory concentration (MIC) of SLMs loaded with OA and UA was 40 µg/mL SLMs + 20 µg/mL OA + 20 µg/mL UA for drug-sensitive Mtb and 80 µg/mL SLMs + 40 µg/mL OA + 40 µg/mL UA for multidrug-resistant (MDR) Mtb. These SLMs showed an efficient reduction in Mtb burden in infected alveolar macrophages. In a murine model of late-stage progressive MDR-TB, aerosolized delivery of SLMs containing OA and UA via a metered-dose inhaler significantly reduced pulmonary bacterial loads and extended survival. In vivo, acute toxicity studies revealed no mortality or signs of toxicity. These findings demonstrate that SLMs are an optimal delivery system for terpenoids, providing potent in vitro and in vivo anti-TB activity with an excellent safety profile. Full article

The rise of antimicrobial resistance (AMR) has become a critical health challenge. This, plus the antimicrobial discovery void, had led scientists to search for an effective alternative to antimicrobials. In this context, nanomaterials, such as graphene oxide (GO), a two-dimensional (2D) carbon molecule with oxidized functional groups, have been shown to interact physically and chemically with bacteria. Moreover, the addition of polyethylene glycol (PEG) to its surface enhances GO’s biocompatibility and water solubility, making it a promising candidate for biomedical applications. This study evaluates the antimicrobial efficacy of GO and its polyethylene glycol-modified form (GO-PEG) against Staphylococcus aureus, a bacterium responsible for numerous hospital-acquired and multidrug-resistant infections. After their production, both nanomaterials were characterized using various techniques to provide insight into their morphology, stability, and functional group composition. Then, the antimicrobial activity of GO and GO-PEG was assessed using the Müeller–Hinton broth microdilution method, determining the minimum inhibitory concentration (MIC) for S. aureus among ten different concentrations of both nanomaterials (from 0.0625 to 32 mg/mL). The results demonstrate the potential of GO as an effective antimicrobial agent at 16 and 32 mg/mL, offering new strategies in the fight against AMR. Further research could establish its role in future therapeutic applications. Full article

Background: Multidrug-resistant Acinetobacter baumannii (CRAB) infections are a serious problem in critical care. This study aims to develop an early prognostic score for immune paralysis, using practical and cost-effective parameters, to predict ICU mortality in patients with CRAB infections being treated with Cefiderocol. Methods: We carried out an observational pilot study on consecutive patients hospitalized in the ICU with ensuing septic Acinetobacter baumannii infections treated with Cefiderocol monotherapy or Cefiderocol including combinations. We investigated the predictive power of lymphocyte counts, lymphocyte subpopulations, serum cholinesterase levels, and reactivation of herpes viruses. Results: Overall, 36 of 39 patients entered in our analysis: 20 survivors and 16 deceased. A total of 12 patients developed bacteremia, 19 patients had HAP/VAP, and 5 patients had a soft tissue infection. Univariate analyses of factors associated with unfavorable outcome revealed a significant association for age (OR: 1.5, CI: 1.11–2.02), SAPS II (OR: 1.05, CI: 1.01–1.1), SOFA score (OR: 1.37, CI: 1.06–1.76), lymphocytopenia (OR: 32.5, CI: 3.45–306.4), viral reactivation (OR: 9.75, CI: 1.72–55.4), and cholinesterase drop <1600 U/L (OR: 39.7, CI: 5.8–271.6). At variance, monotherapy or associations with Cefiderocol were not associated. In the final multivariable model, the only independent predictors of death were age (OR: 1.42, CI: 0.98–2.05), lymphocytopenia (OR: 18.2, CI: 0.87–371), and cholinesterase drop to below 1600 U/L (OR: 9.7, CI: 0.77–123.7). Conclusions: Age, lymphocytopenia, and serum cholinesterase drops, which were nearly significantly associated with an unfavorable outcome, may help pinpoint patients with acute immune paralysis during sepsis. Knowledge of such an immune state may in turn directly influence patients’ care. Full article

Infectious diseases continue to cause global morbidity and mortality. The rise of drug-resistant pathogens is a major challenge to modern medicine. Plant-based antimicrobials may solve this issue; hence, this review discussed in detail plant-sourced antimicrobial drugs as an alternative toward bacterial, fungal, and viral pathogens. Plant-derived chemicals from various sources such as marine, medicinal, and non-medicinal sources have diverse antimicrobial properties. Complex chemical profiles from these sources allow these molecules to interact with several targets in the microbial pathogens. Due to their multi-component composition, these compounds are more effective and less likely to acquire resistance than single-target antibiotics. Medicinal herbs have long been used for their antimicrobial properties; however, non-medicinal plants have also been identified for their antimicrobial properties. Other interesting new pathways for the identification of antimicrobials include marine plants, which contain a wide variety of metabolites that are both distinct and varied. We have conducted a thorough literature search for the medicinal, non-medicinal, and marine plant-derived molecules with antimicrobial roles from databases which include Scopus, PubMed, Google Scholar, and Web of Science. The review also discussed the synergistic potential of combining these plant-derived compounds with traditional antimicrobial drugs to attenuate the microbial pathogenesis. Based on the existing research and advancements, the review article emphasizes the importance of continuing research into plant-based antimicrobials from these many sources and integrating them with existing therapies to combat the rising threat of drug-resistant infections. Full article

Polymyxin antibiotics B and colistin are considered drugs of last resort for the treatment of multi-drug and carbapenem-resistant Gram-negative bacteria. With the emergence and dissemination of multi-drug resistance, monitoring the use and resistance to polymyxins imparted by mobilised colistin resistance genes (mcr) is becoming increasingly important. The Aeromonas genus is widely disseminated throughout the environment and serves as a reservoir of mcr–3, posing a significant risk for the spread of resistance to polymyxins. Recent phylogenetic studies and the identification of insertion elements associated with mcr–3 support the notion that Aeromonas spp. may be the evolutionary origin of the resistance gene. Furthermore, mcr–3-related genes have been shown to impart resistance in naïve E. coli and can increase the polymyxin MIC by up to 64-fold (with an MIC of 64 mg/L) in members of Aeromonas spp. This review will describe the genetic background of the mcr gene, the epidemiology of mcr-positive isolates, and the relationship between intrinsic and transferable mcr resistance genes, focusing on mcr–3 and mcr–3-related genes. Full article

Seagulls are synanthropic wild birds that can contaminate, through their droppings, beaches, urban and peri-urban environments. This concern is more serious when seagulls eliminate antimicrobial-resistant pathogenic bacteria. This study analyzed the fecal samples from 137 yellow-legged seagulls (Larus michahellis) from Central Italy. A total of 218 Escherichia coli strains were isolated and analyzed for phenotypic and genotypic antimicrobial resistance and to identify the virulence genes characterizing different pathotypes. The disk diffusion method on all isolates found relevant resistance rates to ampicillin (38.99%), tetracycline (23.85%), and enrofloxacin (21.10%). On the basis of all results obtained with this test, 62 (28.44%) isolates were classified as multidrug-resistant (MDR) and 6 (2.75%) as extensive drug-resistant (XDR). Molecular analyses conducted on the strains phenotypically resistant to carbapenems, cephalosporins, and penicillins found 9/37 (24.32%) strains positive for bla_OXA-48, 52/103 (50.49%) for bla_TEM, 12/103 (11.65%) for bla_CMY2, 3/103 (2.91%) for bla_CTX, and 1/103 (0.97%,) for bla_SHV. PCR to detect virulence genes characterizing different pathotypes found that 40 (18.35%) isolates had the astA gene, indicative of the enteroaggregative (EAEC) pathotype, 2 (0.92%) had cnf1, 2 (0.92%) had cnf2, and 1 (0.46%) had cdt-IV. All five (2.29%) strains were reportable as necrotoxigenic (NTEC), while 4 (1.83%) had both eaeA and escV, reportable as enteropathogenic (EPEC). Measures to limit seagulls’ access where humans and other animals reside are pivotal to reduce the risk of infection with antimicrobial-resistant and pathogenetic E. coli strains. Full article

Triple-negative breast cancer (TNBC) is associated with a generally poor prognosis due to its highly aggressive and metastatic nature, lack of targetable receptors, as well as the frequent development of resistance to chemotherapy. We previously reported that AU1, a small molecule developed as an inhibitor of BPTF (bromodomain PHD finger-containing transcription factor), was capable of sensitizing preclinical models of TNBC to chemotherapy in part via the promotion of autophagy. In studies reported here, we identify an additional property of this compound, specifically that sensitization is associated with the inhibition of the P-glycoprotein (P-gp) efflux pump. In silico molecular docking studies indicate that AU1 binds to active regions of the efflux pump in a manner consistent with the inhibition of the pump function. This work identifies a novel chemical structure that can influence multidrug efflux, an established mechanism of drug resistance in TNBC, that has not yet been successfully addressed by clinical efforts. Full article

Trichophyton indotineae is an emerging pathogen causing recalcitrant skin infections and exhibiting multiple resistances to azoles and allylamines. Squalene epoxidase erg1^Ala448Thr mutants often show association with azole resistance. RT-PCR gene expression analysis helps to elucidate the connection between ergosterol biosynthesis regulation and efflux control through the activation of multidrug resistance (MDR) and major facilitator superfamily (MFS1) transporters as well as heat shock proteins (HSP). Several T. indotineae isolates demonstrated a heat-dependent increase of Erg11B transcripts combined with downregulation of Erg1, suggesting a protective role for Erg11B. They also showed persistent upregulation of MFS1. The addition of fluconazole or voriconazole induced the expression of Erg11A, MDR3 and, to a lesser extent, Erg11B and Erg1. The azole-resistant erg1^Ala448Thr mutant UKJ 476/21 exhibited exceptionally high transcript levels of sterol 14-αdemethylase Erg11B, combined with the inability of HSP60 and HSP90 to respond to increasing growth temperatures. Itraconazole demonstrated similar effects in a few T. indotineae isolates, but terbinafine did not enhance Erg1 transcription at all. Overexpression of Erg11B may explain the multiple azole resistance phenotype, whereas Erg11B point mutations are not associated with resistance to azoles used for medical treatment. Full article

Major efforts have been made to reduce the use of colistin in livestock since the discovery of the plasmid-borne mobile colistin resistance (mcr) gene in E. coli a decade ago, to curb the burden of its potential transmission to other bacterial species, spread between animals, humans and the environment. This study explored the longitudinal prevalence and characteristics of colistin-resistant and extended-spectrum beta-lactamase-producing (ESBL) E. coli via in vivo fecal and ex vivo carcass swabs from two batches of conventional indoor and organic outdoor Wallon meat sheep from birth to slaughter in 2020 and 2021. Antimicrobial susceptibility testing via broth microdilution revealed that n = 16/109 (15%) E. coli isolates from conventional meat lamb fecal samples had a reduced colistin sensitivity (MIC = 0.5 μg/mL) and thereof, n = 9/109 (8%) were multi-drug-resistant E. coli, while no resistant isolates were recovered from their carcasses. Sequencing revealed causative pmrB genes, indicating that the reduced sensitivity to colistin was not plasmid-borne. While the sample size was small (n = 32), no colistin-resistant and ESBL-producing E. coli were isolated from the organic meat sheep and their carcasses, potentially due to the different husbandry conditions. Prudent and judicious antimicrobial use and strict slaughter hygiene remain imperative for effective risk management to protect consumers in a sustainable One Health approach. Full article