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Veterinary Medicine and Science Jul 2024Salmonellosis is one of the most common food-borne diseases in industrialised and developing countries. In recent year, an increase in antimicrobial resistance among...
BACKGROUND
Salmonellosis is one of the most common food-borne diseases in industrialised and developing countries. In recent year, an increase in antimicrobial resistance among different Salmonella serotypes has been observed.
OBJECTIVE
A cross-sectional study was conducted to assess the prevalence and antimicrobial susceptibility of Salmonella isolated from local chicken eggs in four selected towns in Ethiopia.
METHODS
A total of 115 eggs were examined to detect Salmonella by using standard microbiological methods. The susceptibilities of the isolates to nine antimicrobials were tested by the Kirby-Bauer disk diffusion method.
RESULT
The study revealed that of the 115 eggs examined, 22 (19.1%) were positive for Salmonella of which 14 (12.2%) and 8 (7%) of the isolates were from shells and contents, respectively. The occurrence of Salmonella in egg shells and content and between different altitudes did not differ significantly (p > 0.05). Most isolates were resistant to more than three antimicrobials with a high resistance to kanamycin, ampicillin, nalidixic acid, cotrimoxazole, oxytetracycline and chloramphenicol.
CONCLUSION
The results indicate the potential importance of local chicken eggs as source of multiple antimicrobial-resistant salmonellae and the need for proper cooking before consumption. Further studies are required to describe the epidemiology of Salmonella in various agroclimatic zones of Ethiopia.
Topics: Animals; Ethiopia; Chickens; Salmonella; Prevalence; Cross-Sectional Studies; Anti-Bacterial Agents; Poultry Diseases; Eggs; Drug Resistance, Bacterial; Salmonella Infections, Animal; Food Microbiology
PubMed: 38946179
DOI: 10.1002/vms3.1529 -
Experimental & Molecular Medicine Jul 2024The development of chemoresistance is a major challenge in the treatment of several types of cancers in clinical settings. Stemness and chemoresistance are the chief... (Review)
Review
The development of chemoresistance is a major challenge in the treatment of several types of cancers in clinical settings. Stemness and chemoresistance are the chief causes of poor clinical outcomes. In this context, we hypothesized that understanding the signaling pathways responsible for chemoresistance in cancers is crucial for the development of novel targeted therapies to overcome drug resistance. Among the aberrantly activated pathways, the PI3K-Akt/Wnt/β-catenin signaling pathway is clinically implicated in malignancies such as colorectal cancer (CRC) and glioblastoma multiforme (GBM). Aberrant dysregulation of phospholipase D (PLD) has been implicated in several malignancies, and oncogenic activation of this pathway facilitates tumor proliferation, stemness, and chemoresistance. Crosstalk involving the PLD and Wnt/β-catenin pathways promotes the progression of CRC and GBM and reduces the sensitivity of cancer cells to standard therapies. Notably, both pathways are tightly regulated and connected at multiple levels by upstream and downstream effectors. Thus, gaining deeper insights into the interactions between these pathways would help researchers discover unique therapeutic targets for the management of drug-resistant cancers. Here, we review the molecular mechanisms by which PLD signaling stimulates stemness and chemoresistance in CRC and GBM. Thus, the current review aims to address the importance of PLD as a central player coordinating cross-talk between the PI3K/Akt and Wnt/β-catenin pathways and proposes the possibility of targeting these pathways to improve cancer therapy and overcome drug resistance.
PubMed: 38945955
DOI: 10.1038/s12276-024-01260-9 -
International Journal of Infectious... Jun 2024Hospitalised neonates are vulnerable to infection and have high rates of antibiotic utilisation.
Prospective antimicrobial stewardship interventions by multidisciplinary teams to reduce neonatal antibiotic use in South Africa: the Neonatal Antimicrobial Stewardship (NeoAMS) study.
BACKGROUND
Hospitalised neonates are vulnerable to infection and have high rates of antibiotic utilisation.
METHODS
Fourteen South African neonatal units (seven public, seven private sector) assembled multidisciplinary teams involving neonatologists, microbiologists, pharmacists, and nurses to implement prospective audit and feedback neonatal antimicrobial stewardship (NeoAMS) interventions. The teams attended seven online training sessions. Pharmacists conducted weekday antibiotic prescription reviews in the neonatal intensive care unit and/or neonatal wards providing feedback to the clinical teams. Anonymised demographic and NeoAMS interventions data were aggregated for descriptive purposes and statistical analysis.
FINDINGS
During the 20-week NeoAMS intervention in 2022, 565 neonates were enrolled. Pharmacists evaluated seven hundred antibiotic prescription episodes; rule-out sepsis (180; 26%) and culture-negative sepsis (138; 20%) were the most frequent indications for antibiotic prescription. For infection episodes with an identified pathogen, only 51% (116/229) of empiric treatments provided adequate antimicrobial coverage. Pharmacists recommended 437 NeoAMS interventions (0·6 per antibiotic prescription episode), with antibiotic discontinuation (42%), therapeutic drug monitoring (17%), and dosing (15%) recommendations most frequent. Neonatal clinicians' acceptance rates for AMS recommendations were high (338; 77%). Mean antibiotic length of therapy decreased by 24% from 9·1 to 6·9 days (0·1 day decrease per intervention week; p=0·001), with the greatest decline in length of therapy for culture-negative sepsis (8·2 days (95%CI 5·7-11·7) to 5·9 days (95% CI 4·6-7·5); p=0·032).
INTERPRETATION
This neonatal AMS programme was successfully implemented in heterogenous and resource-limited settings. Pharmacist-recommended AMS interventions had high rates of clinician acceptance. The NeoAMS intervention significantly reduced neonatal antibiotic use, particularly for culture-negative sepsis.
FUNDING
A grant from Merck provided partial support.
PubMed: 38945432
DOI: 10.1016/j.ijid.2024.107158 -
Biochemical Pharmacology Jun 2024The emergence of multidrug-resistant fungi is of grave concern, and its infections are responsible for significant deaths among immunocompromised patients. The treatment... (Review)
Review
The emergence of multidrug-resistant fungi is of grave concern, and its infections are responsible for significant deaths among immunocompromised patients. The treatment of fungal infections primarily relies on a clinical class of antibiotics, including azoles, polyenes, echinocandins, polyketides, and a nucleotide analogue. However, the incidence of fungal infections is increasing as the treatment for human and plant fungal infections overlaps with antifungal drugs. The need for new antifungal agents acting on different targets than known targets is undeniable. Also, the pace at which loss of fungal susceptibility to antibiotics cannot be undermined. There are several modes by which fungi can develop resistance to antibiotics, including reduced drug uptake, drug target alteration, and a reduction in the cellular concentration of the drug due to active extrusions and biofilm formation. The efflux pump's overexpression in the fungi primarily reduced the antibiotic's concentration to a sub-lethal concentration, thus responsible for developing resistant fungus strains. Several strategies are used to check antibiotic resistance in multi-drug resistant fungi, including synthesizing antibiotic analogs and giving antibiotics in combination therapies. Among them the efflux pump protein inhibitors are considered potential adjuvants to antibiotics and can block the efflux of antibiotics by inhibiting efflux pump protein transporters. Moreover, it can sensitize the antifungal drugs to multi-drug resistant fungi with overexpressed efflux pump proteins. This review discusses the natural lead molecules, repurposable drugs, and formulation strategies to overcome the efflux pump activity in the fungi.
PubMed: 38945275
DOI: 10.1016/j.bcp.2024.116400 -
The Science of the Total Environment Jun 2024The presence of antibiotic resistance genes (ARGs), disinfectant resistance genes (DRGs), and pathogens in animal food processing environments (FAPE) poses a significant...
The presence of antibiotic resistance genes (ARGs), disinfectant resistance genes (DRGs), and pathogens in animal food processing environments (FAPE) poses a significant risk to human health. However, knowledge of the contamination and risk profiles of a typical commercial pig slaughterhouse with periodic disinfectant applications is limited. By creating the overall metagenomics-based behavior and risk profiles of ARGs, DRGs, and microbiomes in a nine-section pig slaughterhouse, an important FAPE in China. A total of 454 ARGs and 84 DRGs were detected in the slaughterhouse with resistance genes for aminoglycosides and quaternary ammonium compounds, respectively. The entire slaughtering chain is a hotspot for pathogens, including 83 human pathogenic bacteria (HPB), with 47 core HPB. In addition, 68 high-risk ARGs were significantly correlated with 55 HPB, 30 of which were recognized as potential bacteria co-resistant to antibiotics and disinfectants, confirm a three-fold risk of ARGs, DRGs, and pathogens prevailing throughout the chain. Pre-slaughter pig house (PSPH) was the major risk source for ARGs, DRGs, and HPB. Moreover, 75 Escherichia coli and 47 Proteus mirabilis isolates showed sensitivity to potassium monopersulfate and sodium hypochlorite, suggesting that slaughterhouses should use such related disinfectants. By using whole genome multi-locus sequence typing and single nucleotide polymorphism analyses, genetically closely related bacteria were identified across distinct slaughter sections, suggesting bacterial transmission across the slaughter chain. Overall, this study underscores the critical role of the PSPH section as a major source of HPB, ARGs, and DRGs contamination in commercial pig slaughterhouses. Moreover, it highlights the importance of addressing clonal transmission and cross-contamination of antibiotic- and disinfectant-resistant bacteria within and between slaughter sections. These issues are primarily attributed to the microbial load carried by animals before slaughter, carcass handling, and content exposure during visceral treatment. Our findings provide valuable insights for One Health-oriented slaughterhouse management practices.
PubMed: 38945230
DOI: 10.1016/j.scitotenv.2024.174222 -
Computerized Medical Imaging and... Jun 2024Despite sharing the same histologic classification, individual tumors in multi metastatic patients may present with different characteristics and varying sensitivities...
Despite sharing the same histologic classification, individual tumors in multi metastatic patients may present with different characteristics and varying sensitivities to anticancer therapies. In this study, we investigate the utility of radiomic biomarkers for prediction of lesion-specific treatment resistance in multi metastatic leiomyosarcoma patients. Using a dataset of n=202 lung metastases (LM) from n=80 patients with 1648 pre-treatment computed tomography (CT) radiomics features and LM progression determined from follow-up CT, we developed a radiomic model to predict the progression of each lesion. Repeat experiments assessed the relative predictive performance across LM volume groups. Lesion-specific radiomic models indicate up to a 4.5-fold increase in predictive capacity compared with a no-skill classifier, with an area under the precision-recall curve of 0.70 for the most precise model (FDR = 0.05). Precision varied by administered drug and LM volume. The effect of LM volume was controlled by removing radiomic features at a volume-correlation coefficient threshold of 0.20. Predicting lesion-specific responses using radiomic features represents a novel strategy by which to assess treatment response that acknowledges biological diversity within metastatic subclones, which could facilitate management strategies involving selective ablation of resistant clones in the setting of systemic therapy.
PubMed: 38945043
DOI: 10.1016/j.compmedimag.2024.102413 -
European Journal of Medicinal Chemistry Jun 2024The global microbial resistance is a serious threat to human health, and multitargeting compounds are considered to be promising to combat microbial resistance. In this...
Synthesis and antibacterial medicinal evaluation of carbothioamido hydrazonyl thiazolylquinolone with multitargeting antimicrobial potential to combat increasingly global resistance.
The global microbial resistance is a serious threat to human health, and multitargeting compounds are considered to be promising to combat microbial resistance. In this work, a series of new thiazolylquinolones with multitargeting antimicrobial potential were developed through multi-step reactions using triethoxymethane and substituted anilines as start materials. Their structures were confirmed by H NMR, C NMR and HRMS spectra. Antimicrobial evaluation revealed that some of the target compounds could effectively inhibit microbial growth. Especially, carbothioamido hydrazonyl aminothiazolyl quinolone 8a showed strong inhibitory activity toward drug-resistant Staphylococcus aureus with MIC value of 0.0047 mM, which was 5-fold more active than that of norfloxacin. The highly active compound 8a exhibited negligible hemolysis, no significant toxicity in vitro and in vivo, low drug resistance, as well as rapidly bactericidal effects, which suggested its favorable druggability. Furthermore, compound 8a was able to effectively disrupt the integrity of the bacterial membrane, intercalate into DNA and inhibit the activity of topoisomerase IV, suggesting multitargeting mechanism of action. Compound 8a could form hydrogen bonds and hydrophobic interactions with DNA-topoisomerase IV complex, indicating the insertion of aminothiazolyl moiety was beneficial to improve antibacterial efficiency. These findings indicated that the active carbothioamido hydrazonyl aminothiazolyl quinolone 8a as a chemical therapeutic candidate demonstrated immense potential to tackle drug-resistant bacterial infections.
PubMed: 38944934
DOI: 10.1016/j.ejmech.2024.116626 -
Mymensingh Medical Journal : MMJ Jul 2024Antibiotics' usefulness is threatened by multi-drugs resistance in harmful microorganisms because of abuse and regulatory problems. Emerging microbes, resistance...
Antibiotics' usefulness is threatened by multi-drugs resistance in harmful microorganisms because of abuse and regulatory problems. Emerging microbes, resistance mechanisms and antimicrobial drugs all require extensive investigation. Evaluation of the in vitro antibacterial activity of Methanolic extracts isolated from Black pepper seeds (Piper nigrum L.) against two infection causing pathogens, Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa. From July 2022 and June 2023, this experimental study was conducted at the Mymensingh Medical College's Department of Pharmacology and Therapeutics in conjunction with the Department of Microbiology. The solvents Methanol and 10.0% Di-Methyl Sulfoxide (DMSO) were used to make the extract. Using the disc diffusion and broth dilution methods, the antibacterial activity of methanolic extract of black pepper seeds (MBPE) was evaluated at various doses. Using the broth dilution procedure, the conventional antibiotic Ciprofloxacin was utilized, and the outcome was contrasted with that of Methanol extracts. Methanolic extract of black pepper seeds (MBPE) at seven distinct concentrations (100, 80, 60, 40, 20, 10 and 5mg/ml) were utilized, then later in chosen concentrations as needed to confirm the extracts' more precise margin of antimicrobial sensitivity. At 80mg/ml and above doses of the MBPE, it had an inhibitory impact against the aforementioned microorganisms. For Staphylococcus aureus and Pseudomonas aeruginosa the MIC were 60 and 70mg/ml in MBPE respectively. As of the MIC of Ciprofloxacin was 1μg/ml against Staphylococcus aureus and 1.5μg/ml for Pseudomonas aeruginosa. In comparison to MICs of MBPE for the test organisms, the MIC of Ciprofloxacin was the lowest. This study clearly shows that Staphylococcus aureus and Pseudomonas aeruginosa are sensitive to the methanolic extract of black pepper seeds' antibacterial properties.
Topics: Piper nigrum; Pseudomonas aeruginosa; Plant Extracts; Staphylococcus aureus; Seeds; Anti-Bacterial Agents; Microbial Sensitivity Tests; Methanol
PubMed: 38944702
DOI: No ID Found -
Nature Communications Jun 2024Real-time genomics through nanopore sequencing holds the promise of fast antibiotic resistance prediction directly in the clinical setting. However, concerns about the...
Real-time genomics through nanopore sequencing holds the promise of fast antibiotic resistance prediction directly in the clinical setting. However, concerns about the accuracy of genomics-based resistance predictions persist, particularly when compared to traditional, clinically established diagnostic methods. Here, we leverage the case of a multi-drug resistant Klebsiella pneumoniae infection to demonstrate how real-time genomics can enhance the accuracy of antibiotic resistance profiling in complex infection scenarios. Our results show that unlike established diagnostics, nanopore sequencing data analysis can accurately detect low-abundance plasmid-mediated resistance, which often remains undetected by conventional methods. This capability has direct implications for clinical practice, where such "hidden" resistance profiles can critically influence treatment decisions. Consequently, the rapid, in situ application of real-time genomics holds significant promise for improving clinical decision-making and patient outcomes.
Topics: Klebsiella pneumoniae; Genomics; Humans; Anti-Bacterial Agents; Klebsiella Infections; Drug Resistance, Multiple, Bacterial; Plasmids; Nanopore Sequencing; Genome, Bacterial; Microbial Sensitivity Tests
PubMed: 38944650
DOI: 10.1038/s41467-024-49851-4 -
Chemosphere Jun 2024Colistin is a polymyxin antimicrobic mainly used to treat infection caused by multi-drug resistant Gram-negative bacteria. Mechanisms of colistin resistance are linked...
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.
PubMed: 38944352
DOI: 10.1016/j.chemosphere.2024.142717