High Resistance Rates Research Articles

Macrolide Resistance in the Aerococcus urinae Complex: Implications for Integrative and Conjugative Elements.

The recognition of the Aerococcus urinae complex (AUC) as an emerging uropathogen has led to growing concerns due to a limited understanding of its disease spectrum and antibiotic resistance profiles. Here, we investigated the prevalence of macrolide resistance within urinary AUC isolates, shedding light on potential genetic mechanisms. Phenotypic testing revealed a high rate of macrolide resistance: 45%, among a total of 189 urinary AUC isolates. Genomic analysis identified integrative and conjugative elements (ICEs) as carriers of the macrolide resistance gene ermA, suggesting horizontal gene transfer as a mechanism of resistance. Furthermore, comparison with publicly available genomes of related pathogens revealed high ICE sequence homogeneity, highlighting the potential for cross-species dissemination of resistance determinants. Understanding mechanisms of resistance is crucial for developing effective surveillance strategies and improving antibiotic use. Furthermore, the findings underscore the importance of considering the broader ecological context of resistance dissemination, emphasizing the need for community-level surveillance to combat the spread of antibiotic resistance within the urinary microbiome.

Prevalence of multi-drug resistant bacteria in intensive care units at Tripoli University Hospital, Tripoli, Libya

ABSTRACT Among hospitalized patients worldwide, infections caused by multidrug-resistant (MDR) bacteria are a major cause of morbidity and mortality. This study aimed to isolate MDR bacteria from five intensive care units (ICUs) at Tripoli University Hospital (TUH). A prospective cross-sectional study was conducted over a seven-month period (September 2022 to March 2023) across five ICUs at TUH. A total of 197 swabs were collected from Patients’, healthcare workers’ and ICUs equipment. Samples collected from patients were nasal swabs, oral cavity swabs, hand swabs, sputum specimens, skin swabs, umbilical venous catheter swabs, and around cannula. Swabs collected from health care workers were nasal swabs, whereas ICUs equipment’s samples were from endotracheal tubes, oxygen masks, and neonatal incubators. Identification and antimicrobial susceptibility test was confirmed by using MicroScan auto SCAN 4 (Beckman Coulter). The most frequent strains were Gram negative bacilli 113 (57.4%) with the predominance of Acinetobacter baumannii 50/113 (44%) followed by Klebsiella pneumoniae 44/113 (40%) and Pseudomonas aeruginosa 6/113 (5.3%). The total Gram positive bacterial strains isolated were 84 (42.6%), coagulase negative Staphylococci 55 (66%) with MDRs (89%) were the most common isolates followed by Staphylococcus aureus 15 (17.8%). Different antibiotics were used against these isolates; Gram- negative isolates showed high resistance rates to ceftazidime, gentamicin, amikacin and ertapenem. A. baumannii were the most frequent MDROs (94%), and the highest resistance rates in Gram-positive strains were observed toward ampicillin, oxacillin, ampicillin/sulbactam and Cefoxitin, representing 90% of total MDR Gram-positive isolates. ESBL and MRS were identified in most of strains. The prevalence of antibiotic resistance was high for both Gram negative and Gram positive isolates. This prevalence requires strict infection prevention and control intervention, continuous monitoring, implementation of effective antibiotic stewardship, immediate, concerted and collaborative action to monitor its prevalence and spread in the hospital.

Antimicrobial susceptibility and genomic characterization of Vibrio parahaemolyticus isolated from aquatic foods in 15 provinces, China, 2020

Prevalent in marine, estuarine and coastal environments, Vibrio parahaemolyticus is one of the major foodborne pathogens which can cause acute gastroenteritis through consumption of contaminated food. This study encompassed antimicrobial resistance, molecular characteristics and phylogenetic relationships of 163 V. parahaemolyticus isolated from aquatic foods across 15 provinces in China. The isolates showed high resistance rates against ampicillin (90.80 %, 148/163) and cefazolin (72.39 %, 118/163). Only 5 isolates demonstrated multi-drug resistance (MDR) phenotypes. A total of 37 different antibiotic resistance genes (ARGs) in correlation with seven antimicrobial categories were identified. tet(34) and tet(35) were present in all 163 isolates. Other most prevalent ARGs were those conferring resistance to β-lactams, with prevalence rate around 18.40 % (30/163). The virulence genes tdh and trh were found in 17 (10.43 %) and 9 (5.52 %) isolates, respectively. Totally 121 sequence types (STs) were identified through whole genome analysis, among which 60 were novel. The most prevalent sequence type was ST3 (9.20 %, 15/163), which shared the same genotype profile of trh_, tdh+ and blaCARB-22+. Most of the tdh+V. parahaemolyticus isolates was clustered into a distinctive clade by the phylogenetic analysis. Our study showed that the antimicrobial resistance of V. parahaemolyticus in aquatic foods in China was moderate. However, the emerging of MDR isolates implicate strengthened monitoring is needed for the better treatment of human V. parahaemolyticus infections. High genetic diversity and virulence potential of the isolates analyzed in this study help better understanding and evaluating the risk of V. parahaemolyticus posed to public health.

Clinical characteristics and antimicrobial susceptibility profiles of Mycobacterium abscessus and Mycobacterium massiliense pulmonary infection

ObjectivesMycobacterium abscessus complex (MABC) is the most common rapidly growing Mycobacterium species in structural pulmonary diseases and can be life-threatening. This study aimed to assess the clinical characteristics and drug-susceptibility statuses of different M. abscessus (MAB) subspecies in the Zhejiang Province. MethodsDNA sequencing was used to differentiate clinical MABC subspecies isolates. The Clinical and Laboratory Standards Institute guidelines were used to determine in vitro susceptibility of imipenem-relebactam (IMP-REL), omadacycline, and other conventional antibiotics. Patient clinical characteristics were collected and analysed. ResultsIn total, 139 M. abscessus, 39 Mycobacterium massiliense, and 1 Mycobacterium bolletii isolates were collected, accounting for 77.7%, 21.8%, and 0.5% of the MABC isolates, respectively. Patients with M. abscessus pulmonary disease (M.ab-PD) had higher proportions of older adults, tuberculosis history, chronic pulmonary disease, and malignancy than those with M. massiliense pulmonary disease (M.ma-PD). Patients with M.ab-PD had higher rates of bilateral middle- and lower-lobe involvement than patients with M.ma-PD. Both subspecies showed high resistance rates to doxycycline and moxifloxacin, and clarithromycin-induced resistance was more common in M.ab than in M.ma. IMP-REL resulted in a twofold reduction in the minimum inhibitory concentration (MIC) value compared with imipenem alone among MAB; furthermore, the MIC was lower in M.ab than in M.ma. Omadacycline and tigecycline had comparable in vitro susceptibility, and the MIC showed no statistically significant difference between M.ab and M.ma. ConclusionsM.ab is the most prevalent MABC subspecies in the Zhejiang Province. Patients with M.ab-PD have complex underlying diseases and broader lobar lesions. IMP-REL and omadacycline are promising antibiotics for MABC infection treatment.

Epidemiological and genetic characterization of multidrug-resistant non-O1 and non-O139 Vibrio cholerae from food in southern China

This study reports a comprehensive epidemiological and genetic analysis of V. cholerae strains, specifically non-O1/non-O139 serogroups, isolated from animal-derived food samples in Guangdong province from 2015 to 2019. A total of 21 V. cholerae strains were obtained, which exhibited high resistance rates for nalidixic acid (57.14 %, 12/21), ampicillin (33.33 %, 7/21), and ciprofloxacin (19.05 %, 4/21). The quinolone resistance-related gene, qnrVC, was prevalent in 80.95 % (17/21) of the isolates. Additionally, chromosomally mediated quinolone-resistance mutations, including mutations in GyrA at position 83 (S83I) and ParC at position 85 (S85L), were detected in 47.62 % of the isolates. The combination of target mutation and qnrVC genes was shown to mediate resistance or intermediate resistance to ciprofloxacin in V. cholerae. Furthermore, an IncC-type conjugative plasmid carrying thirteen antibiotic resistance genes, including genes conferring resistance to two clinically important antibiotics, cephalosporins and fluoroquinolones, was identified in the shrimp-derived strain Vc516. While none of our food isolates harbored the toxigenic CTX- and TCP-encoding genes, they did possess genes encoding toxins such as HlyA and Autoinducer-2. Notably, some V. cholerae strains from this study exhibited a close genetic relationship with clinical strains, suggesting their potential to cause human infections. Taken together, this study provides a comprehensive view of the epidemiological features and genetic basis of antimicrobial resistance and virulence potential of V. cholerae strains isolated from food in southern China, thereby advancing our understanding of this important pathogen.

Prevalence and genetic basis of Mycobacterium tuberculosis resistance to pretomanid in China

BackgroundPretomanid is a key component of new regimens for the treatment of drug-resistant tuberculosis (TB) which are being rolled out globally. However, there is limited information on the prevalence of pre-existing resistance to the drug.MethodsTo investigate pretomanid resistance rates in China and its underlying genetic basis, as well as to generate additional minimum inhibitory concentration (MIC) data for epidemiological cutoff (ECOFF)/breakpoint setting, we performed MIC determinations in the Mycobacterial Growth Indicator Tube™ (MGIT) system, followed by WGS analysis, on 475 Mycobacterium tuberculosis (MTB) isolated from Chinese TB patients between 2013 and 2020.ResultsWe observed a pretomanid MIC distribution with a 99% ECOFF equal to 0.5 mg/L. Of the 15 isolates with MIC values > 0.5 mg/L, one (MIC = 1 mg/L) was identified as MTB lineage 1 (L1), a genotype previously reported to be intrinsically less susceptible to pretomanid, two were borderline resistant (MIC = 2–4 mg/L) and the remaining 12 isolates were highly resistant (MIC ≥ 16 mg/L) to the drug. Five resistant isolates did not harbor mutations in the known pretomanid resistant genes.ConclusionsOur results further support a breakpoint of 0.5 mg/L for a non-L1 MTB population, which is characteristic of China. Further, our data point to an unexpected high (14/475, 3%) pre-existing pretomanid resistance rate in the country, as well as to the existence of yet-to-be-discovered pretomanid resistance genes.

Comprehensive Profiling of Klebsiella in Surface Waters from Northern Portugal: Understanding Patterns in Prevalence, Antibiotic Resistance, and Biofilm Formation

This study investigates the prevalence of resistance and virulence genes in Klebsiella isolates from surface waters in Northern Portugal, within the broader context of freshwater quality challenges in Southern Europe. The aim of this research is to explain how Klebsiella dynamics, antibiotic resistance, and biofilm formation interact in surface waters. Antimicrobial susceptibility was examined using the Kirby–Bauer disk diffusion method against 11 antibiotics and screening for Extended-Spectrum Beta-Lactamase (ESBL) production using the double-disk synergy. PCR was employed to detect resistance and virulence genes, while biofilm production was assessed using the microplate method. Out of 77 water isolates, 33 Klebsiella (14 Klebsiella spp. and 19 K. pneumoniae strains) were isolated. ESBL production was observed in 36.8% of K. pneumoniae and 28.6% of Klebsiella spp. High resistance rates to blaCTX-U were observed in both. The papC gene was prevalent, signifying potential environmental risks. Biofilm production averaged 81.3% for K. pneumoniae and 86.9% for Klebsiella spp. These findings underscore the intricate interplay between Klebsiella’s dynamics and freshwater quality, with ESBL’s prevalence raising concerns about waterborne dissemination and public health implications. This work supports the need for vigilance of Klebsiella in surface waters in Southern Europe.

Identification of Potential Breast Cancer Stem Cell Biomarkers in the Secretome Using a Network Interaction Approach Analysis.

Breast cancer stem cells (BCSCs) play a role in the high rates of resistance, recurrence, and metastasis. The precise biomarkers of BCSCs can assist effectively in identifying cancer, assessing prognosis, diagnosing, and monitoring therapy. The aim of this study was to give a complete analysis for predicting specific biomarkers of BCSCs. We aggregated profile datasets in this work to shed light on the underlying critical genes and pathways of BCSCs. We obtained two expression profiling by array datasets (GSE7513 and GSE7515) from the Gene Expression Omnibus (GEO) database to identify biomarkers in BCSCs. Enrichr was used to do functional analysis, including gene ontology (GO) and reactome pathway. Furthermore, the protein-protein interaction (PPI) of these differential expression genes (DEGs) was visualized using Cytoscape with the search tool for the retrieval of interacting genes (STRING). The hub genes in the PPI network were chosen for further investigation. We identified 65 up-regulated and 190 down- regulated DEGs and the GO enrichment analysis revealed that these DEGs were enriched in biological process related to tumorigenesis and stemness, including alter the extracellular matrix's physicochemical properties, cytoskeletal reorganisation, adhesion, motility, migration, growth, and survival. The Reactome analysis indicated that these DEGs were also involved in modulating function of ECM, regulation cancer metabolism and angiogenesis, tumor growth, proliferation, and metastasis. Our bioinformatic study revealed that FYN, INADL, OCLN, F11R, and TOP2A were potential biomarker panel of BCSCs from secretome.

Occurrence, antimicrobial resistance, and molecular characteristics of Salmonella enterica serovar 1,4,[5],12:i:- from food and patients in China

Salmonella enterica serovar Typhimurium monophasic variant 1,4,[5],12:i:- is increasingly responsible for human infections worldwide. However, studies assessing the prevalence and epidemiological characteristics of this emerging serovar are lacking in China. Here, a collection of 125 S. Typhimurium-like strains derived from food and patients in China between 2011 and 2019 were analyzed to investigate the occurrence ratio of S. 1,4,[5],12:i:-. Among them, 23.2% (22/95) of food-related isolates and 70.0% (21/30) of human isolates were assigned as S. 1,4,[5],12:i:-. Only two strains were sequence type (ST) 19; the rest all belonged to ST34. These isolates were further divided into 29 multiple locus variable-number tandem repeat analysis (MLVA) profiles, with the same dominant profile present in both food-source and human isolates. More than 90.0% of S. 1,4,[5],12:i:- isolates were multidrug-resistant. The high prevalence of blaCTX-M (33.3%, 7/21) in extended-spectrum β-lactamase-producing S. 1,4,[5],12:i:- isolates from patients identified here will raise clinical concern over human salmonellosis treatment. Twelve different deletion types of the fljAB operon region associated with the loss of phase 2 flagellar antigen were identified. These results suggested that the Chinese S. 1,4,[5],12:i:- strains consist of multiple distinct clones and their high rates of prevalence and multidrug resistance could constitute potential risks to public health.

Machinability of waste bamboo powder ash reinforced 7075-T651/B4C Hybrid composite in computer numerical control lathe

Metal Matrix Composites (MMC) are novelly prepared with the reinforcement of different wood ash in the matrix material to achieve desired properties. Utilizing the waste material for reinforcement may reduce the material cost. Usually, fly ash from thermal power plants has become a popular reinforcement material for MMC through stir casting and employing in friction stir processing. This research is motivated by using ash of waste bamboo powder (AWBP). The waste of bamboo pieces was collected from the furniture industry. They have been gathered, prepared to ash and used as reinforcement of 4 wt%, 8 wt%, and 10 wt% in stir casting of aluminium alloy 7075-T651 and that was optimized as 8 %. The objective of this research is CNC turning type machinability of AA7075-T651/ B4C/AWBP hybrid Composites. The details of the reinforcement are 2 wt% B4C and 8 wt% AWBP. The effects of such reinforcement in AA7075-T651/ B4C/AWBP hybrid composite have improved the friction and wear behaviours, such as high wear resistance and low wear rate. The composite was cased as circular rods. The CNC turning type machinability was investigated in the CNC turning centre. The cutting speed varied from 1000 rpm to 3500 rpm, the feed rate varied from 100 mm per hour to 200 mm per hour. The Al2O3 nanoparticles concentration on cutting fluids varied from 0.25 wt% to 1 wt%. The response surface methodology was used to optimize the parameters. A mathematical model was developed to predict the responses.

Antibiotic resistance rates of <i>Klebsiella pneumoniae</i> strains isolated from urine cultures

Aim: Our study aimed to determine the antibiotic resistance rates of K. pneumoniae by retrospectively examining the results of urine culture samples studied in our laboratory. Methods: Urine samples with K. pneumoniae growth, sent to our laboratory from various wards, outpatient clinics, and intensive care units between July 1, 2018 and December 31, 2022 were included in the study and retrospectively examined. Results: The antibiotic to which K. pneumoniae was most resistant was cefixime (53.3%), and the antibiotic to which it was least resistant was imipenem (12.1%). While the lowest resistance rates were observed in the samples of outpatients, the highest resistance rates were observed in the samples of ward patients and to cefixime (81%), amoxicillin clavulanic acid (AMC) (80%), trimethoprim-sulfamethoxazole (TMT/SXT) (74.8%), and ciprofloxacin (72.1%). Ertapenem (48.9%), meropenem (50.2%) and piperacillin-tazobactam (PRP) (57.3%) resistance was found to be higher in intensive care patients. Conclusion: Although fluctuations in resistance rates have been observed over the years, resistance rates have generally been found to be high for antibiotics frequently used in the empirical treatment of urinary tract infections. Re-adjusting treatment according to culture results and keeping resistance rates in mind for empirical treatment will be important for treatment success.

A situational analysis of antibiotic prescription, dispensing practices and resistance pattern in Nepal: Are we losing the battle?

Background: Antibiotics are widely utilized to treat infections and provide preventative and therapeutic benefits in animal and human healthcare. However, because of the emergence and spread of resistance mechanisms, which cause bacteria to become less susceptible to antibiotics and other treatments and less effective, antimicrobial resistance (AMR) has grown to be one of the most significant worldwide public health concerns. Low- and middle-income countries (LMICs) such as Nepal have a high rate of infectious illnesses and antibiotic resistance, which can lead to both human and financial losses. Methods: The information for the scenario analysis was acquired through a review of published and grey literature, as well as interviews with important stakeholders from all sectors. Conclusion: Besides knowing all the challenges of antibiotic resistance, the programs assuring towards AMR is conducted in Nepal in very infrequent way. The antibiotic use should be optimize by giving various personalized treatment approaches and accurate diagnosis which plays vital roles in minimizing unnecessary antibiotic prescriptions. We can organize different awareness programs to reduce antibiotic resistance that may enhance the proper use of antibiotic with proper dose and prescription in accordance health care professionals. Interpreting all the problems, government should give more priority to antibiotic resistance and should be able to minimize the problems. If antibiotic resistance is not taken in a very serious way by all the healthcare workers like doctors, nurses, pharmacists, lab technicians, etc. then the battle we are fighting leads to be defeated and problem will never end.

Integrated Proteomics and Protein Co-expression Network Analysis Identifies Novel Epileptogenic Mechanism in Mesial Temporal Lobe Epilepsy.

Over 50 million people worldwide are affected by epilepsy, a common neurological disorder that has a high rate of drug resistance and diverse comorbidities such as progressive cognitive and behavioural disorders, and increased mortality from direct or indirect effects of seizures and therapies. Despite extensive research with animal models and human studies, limited insights have been gained into the mechanisms underlying seizures and epileptogenesis, which has not translated into significant reductions in drug resistance, morbidities, or mortality. To better understand the molecular signaling networks associated with seizures in MTLE patients, we analyzed the proteome of brain samples from MTLE and control cases using an integrated approach that combines mass spectrometry-based quantitative proteomics, differential expression analysis, and co-expression network analysis. Our analyses of 20 human brain tissues from MTLE patients and 20 controls showed the organization of the brain proteome into a network of 9 biologically meaningful modules of co-expressed proteins. Of these, 6 modules are positively or negatively correlated to MTLE phenotypes with hub proteins that are altered in MTLE patients. Our study is the first to employ an integrated approach of proteomics and protein co-expression network analysis to study patients with MTLE. Our findings reveal a molecular blueprint of altered protein networks in MTLE brain and highlight dysregulated pathways and processes including altered cargo transport, neurotransmitter release from synaptic vesicles, synaptic plasticity, proteostasis, RNA homeostasis, ion transport and transmembrane transport, cytoskeleton disorganization, metabolic and mitochondrial dysfunction, blood micro-particle function, extracellular matrix organization, immune response, neuroinflammation, and cell signaling. These insights into MTLE pathogenesis suggest potential new candidates for future diagnostic and therapeutic development.

Should we review our prophylaxis approach for increased antibiotic resistance in transrectal prostate biopsy?

This study aims to show the bacteriologic picture of acute prostatitis and bacteremia caused by infective agent after transrectal ultrasound-guided prostate biopsy (TRUSBx) and to determine the resistance rates of the infections in patients undergoing transrectal biopsy and to guide prophylaxis approach before biopsy. The retrospective data of 935 patients who underwent TRUSBx between January 2010 to January 2019 were reviewed. Pre-biopsy urine cultures and antimicrobial susceptibility were obtained. Subsequently, patients admitted to the hospital with any complaint after biopsy were examined for severe infection complications. Of the 430 (61.7%) patients who underwent urine culture before the procedure, 45 (10.5%) had growth; 30 (66.7%) of the growing microorganisms were Escherichia coli. Twenty (44.4%) of all Gram-negative agents in pre-biopsy urine culture were susceptible to quinolone. Post TRUSBx bacteremia was present in 18.2%, urinary system infection in 83.6%, and hospitalization in 61.8% of 55 patients who were admitted to the hospital. In the isolated gram-negative microorganisms, fluoroquinolones resistance in urinary system infections was seen in 40% and bacteremia was seen in 70% of the cases. ESBL-producing Gram-negative bacteria were determined in 40% of infections in blood and 38.5% of urinary system infections in the post biopsy period in the current study. These high antibiotic resistance rates suggest that we better review our pre-procedure prophylaxis approaches.

Risk factors for bacteremic pneumonia and mortality (28-day mortality) in patients with Acinetobacter baumannii bacteremia

BackgroundPatients infected with Acinetobacter baumannii (AB) bacteremia in hospital have high morbidity and mortality. We analyzed the clinical characteristics of pneumonia and nonpneumonia-related AB bloodstream infections (AB BSIs) and explored the possible independent risk factors for the incidence and prognosis of pneumonia-related AB BSIs.MethodsA retrospective monocentric observational study was performed. All 117 episodes of hospital-acquired AB bacteremia sorted into groups of pneumonia-related AB BSIs (n = 45) and nonpneumonia-related AB BSIs (n = 72) were eligible. Univariate/multivariate logistic regression analysis was used to explore the independent risk factors. The primary outcome was the antibiotic susceptibility in vitro of pneumonia-related AB BSIs group. The secondary outcome was the independent risk factor for the pneumonia-related AB BSIs group.ResultsAmong 117 patients with AB BSIs, the pneumonia-related group had a greater risk of multidrug resistant A. baumannii (MDRAB) infection (84.44%) and carbapenem-resistant A. baumannii (CRAB) infection (80%). Polymyxin, minocycline and amikacin had relatively high susceptibility rates (> 80%) in the nonpneumonia-related group. However, in the pneumonia-related group, only polymyxin had a drug susceptibility rate of over 80%. Univariate analysis showed that survival time (day), CRAB, MDRAB, length of hospital stay prior to culture, length of ICU stay prior to culture, immunocompromised status, antibiotics used prior to culture (n > = 3 types), endotracheal tube, fiberoptic bronchoscopy, PITT, SOFA and invasive interventions (n > = 3 types) were associated with pneumonia-related AB bacteremia. The multivariate logistic regression analysis revealed that recent surgery (within 1 mo) [P = 0.043; 0.306 (0.098–0.962)] and invasive interventions (n > = 3 types) [P = 0.021; 0.072 (0.008–0.671)] were independent risk factors related to pneumonia-related AB bacteremia. Multivariate logistic regression analysis revealed that length of ICU stay prior to culture [P = 0.009; 0.959 (0.930–0.990)] and recent surgery (within 1 mo) [P = 0.004; 0.260 (0.105–0.646)] were independent risk factors for mortality in patients with pneumonia-related AB bacteremia. The Kaplan‒Meier curve and the timing test showed that patients with pneumonia-related AB bacteremia had shorter survival time compared to those with nonpneumonia-related AB bacteremia.ConclusionsOur study found that A. baumannii had a high rate of antibiotic resistance in vitro in the pneumonia-related bacteremia group, and was only sensitive to polymyxin. Recent surgery was a significantly independent predictor in patients with pneumonia-related AB bacteremia.

Prevalence and Antimicrobial Susceptibility Profile of Salmonella from Poultry Farms and In-Contact Humans and Associated Risk Factors in Addis Ababa, Ethiopia.

Poultry and poultry products are the common sources of Salmonella,which is one of the serious food-borne bacterial diseases in humans. Little is known about the status of Salmonella and their antimicrobial susceptibility in poultry farms in Addis Ababa. This study was conducted to estimate the prevalence and antimicrobial susceptibility of Salmonella isolates and to investigate possible risk factors for the occurrence of Salmonella in poultry farms in Addis Ababa. We recruited 58 poultry farms, from which 471 poultry-related samples and 44 stool samples from in-contact humans were collected. The isolates were tested for their susceptibility to 11 antimicrobials using the Kirby-Bauer disk diffusion assay. The farm-level prevalence of Salmonella was 36.2% and the sample-level prevalence was 6.4% for samples taken from poultry farms and 4.5% in human stool samples who have contact with poultry. On-farm waste disposal practices and chicken being purchased from different multiplication farms were significantly associated with Salmonella positivity of the farms (p < 0.05). Eleven (34.4%) Salmonella isolates were resistant to streptomycin, and nine (28.1%) were resistant to tetracycline. Thirteen (40.6%) Salmonella isolates were resistant to two or more antimicrobials tested in this study, whereas resistance to 3 or more antimicrobials was detected in seven (21.9%) isolates. In conclusion, a high prevalence of Salmonella and a high rate of resistance to multiple antimicrobials were detected in poultry farms in Addis Ababa. Hence, implementation of strong biosecurity measures and rational use of antimicrobials are recommended.

Deregulation of New Cell Death Mechanisms in Leukemia.

Hematological malignancies are among the top five most frequent forms of cancer in developed countries worldwide. Although the new therapeutic approaches have improved the quality and the life expectancy of patients, the high rate of recurrence and drug resistance are the main issues for counteracting blood disorders. Chemotherapy-resistant leukemic clones activate molecular processes for biological survival, preventing the activation of regulated cell death pathways, leading to cancer progression. In the past decade, leukemia research has predominantly centered around modulating the well-established processes of apoptosis (type I cell death) and autophagy (type II cell death). However, the development of therapy resistance and the adaptive nature of leukemic clones have rendered targeting these cell death pathways ineffective. The identification of novel cell death mechanisms, as categorized by the Nomenclature Committee on Cell Death (NCCD), has provided researchers with new tools to overcome survival mechanisms and activate alternative molecular pathways. This review aims to synthesize information on these recently discovered RCD mechanisms in the major types of leukemia, providing researchers with a comprehensive overview of cell death and its modulation.

Comparison of the Efficacy of 12-day Concomitant Quadruple Therapy versus 14-day High dose Dual Therapy as a First-line H. pylori Eradication Regimen.

Helicobacter pylori (H. pylori) is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have been used for H. pylori eradication. We aimed to compare the efficacy of two different regimens as first-line H. pylori eradication regimens, in an area with high antibiotic resistance. In this RCT, we assigned 223 patients with H. pylori infection, who were naïve to treatment. They were randomly divided into two groups to receive either 12-day concomitant quadruple therapy (consisting of pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) or 14-day high dose dual therapy (consisting of esomeprazole 40 mg and amoxicillin 1 g TDS). H. pylori eradication was assessed eight weeks after the end of treatment. H. pylori eradication rate by PP analysis for 12-day concomitant quadruple therapy and 14-day high dose dual therapy were 90.4% and 79.1%, respectively (p=0.02). According to ITT analysis, the eradication rates were 86.2% and 76.3%, respectively (p=0.06). Adverse drug reactions were 12.3% in high dose dual therapy and 36.8% in concomitant quadruple therapy (p<0.001). Twelve-day concomitant therapy seems to be an acceptable regimen for first-line H. pylori eradication in Iran, a country with a high rate of antibiotic resistance. Although, high dose dual therapy did not result in an ideal eradication rate, but it had fewer drug side effects than the 12-day concomitant regimen.

Genotypic and phenotypic antimicrobial resistance of Irish Clostridioides difficile isolates, 2022

ObjectivesInfection with Clostridioides difficile usually occurs after antibiotic treatment for other infections and can cause gastro-intestinal disorders of variable severity. C. difficile can be resistant to a wide spectrum of antimicrobials. Detection of antimicrobial resistance (AMR) is important to direct optimal treatment and surveillance of AMR patterns in the overall population. Correlation between genotypic markers and phenotypic AMR is not yet well defined. The aim for this study is to assess whether and to what extent genotypic determinants of AMR correlate with phenotypic resistance. MethodsC. difficile isolates (n = 99) were phenotypically characterized for resistance to eight antibiotics using Sensititre plates or E-tests. Their genomes were screened for genetic markers of resistance. Accuracy, sensitivity, specificity, positive and negative predictive values were calculated. ResultsWe found high rates of resistance (>50 %) to cefoxitin and clindamycin, intermediate rates of resistance (10 %–50 %) to moxifloxacin and tetracycline and low rates of resistance (<10 %) to imipenem, metronidazole, vancomycin, and rifampicin. For moxifloxacin, tetracycline, and clindamycin, we found a good correlation between genotypic and phenotypic AMR, with an overall accuracy of 98 % (95 % CI 93%–100 %), 78 % (95 % CI 68%–86 %) and 86 % (95 % CI 77%–92 %) respectively. For the other five antibiotics, accurate estimates on the correlation could not be made. ConclusionOur results suggest that for moxifloxacin, tetracycline and clindamycin, phenotypic resistance in C. difficile can be predicted by genetic indicators and used for public health purposes. However, for the other five antibiotics, the model is not accurate and further development is necessary.

Antimicrobial Resistance and Molecular Characterization of Escherichia coli from Healthy Chickens in Shandong, China from 2009 to 2014.

Antimicrobial resistance (AMR) is a great threat to animal and public health. Here, we conducted a surveillance of Escherichia coli isolated from healthy chickens during 2009-2014 to identify the characteristics of AMR. A total of 351 (95.64%) E. coli isolates were obtained from 367 healthy chicken fecal samples collected from 6 farms located in Shandong Province, China. The susceptibility to 10 antimicrobials, the prevalence of antibiotic resistance genes (ARGs), phylogenetic clustering, and multilocus sequence typing were evaluated. The isolates exhibited high resistant rates (>95%) to ampicillin, cefotaxime, ciprofloxacin, ceftiofur, and enrofloxacin. The most prevalent ARGs were blaCTX-M (36.36%), aac(6')-Ib-cr (30.79%), qnrS (29.62%), oqxAB (27%), mcr-1 (15.83%), blaTEM (9.09%), qnrC (3.52%), qnrD (0.88%), and qepA (0.29%). Phylogenetic clustering analysis indicated that the most prevalent group was group D (37.89%), followed by group B1 (34.76%), A (24.22%), and B2 (3.13%). Fifty-seven sequence types (STs) were identified among the 124 blaCTX-M-positive strains, and the dominant STs were ST354 (13.71%), ST117 (5.65%), ST155, ST2309, and ST2505 (4.84% each). There was a significant association between 17 pairs of AMR phenotypes, 14 pairs of ARGs, and 11 pairs of AMR-ARGs. The strongest association was found between ST602 and qnrC (odds ratios: 22.2). This study implied that E. coli isolated from healthy chickens could potentially serve as a reservoir of AMR and ARGs, and significant associations exist among AMR, ARGs, phylogenetic groups, and STs. Our study highlighted the need for routine surveillance of AMR in healthy chickens, and promoting appropriate antibiotic use and implementing regular monitoring of resistance in broilers are crucial for fostering the development of the poultry industry and safeguarding public health.