High Resistance Rates Research Articles

Blood Culture Isolates and Antibiogram for Salmonella at Tertiary Care Hospital

Objective: To determine the pattern of blood culture isolates and antibiogram for salmonella at tertiary care hospital and identify frequency of multi-drug resistance and XDR. Methodology: This descriptive, cross-sectional analysis was carried out on enteric fever/salmonella infected patients from 1-02-2020 to 31-10-2020 at Pediatrics Unit – II (Liaquat University Hospital). Children of either gender, aged 1 to 15 years, who presented with fever lasting more than 3 days, abdominal pain, headache, diarrhea, vomiting, or constipation, and who had a positive blood culture for Salmonella, were included. Data was collected into a structured questionnaire, containing enquiries pertaining to basic biodata, sociodemographic details, clinical presentation, and culture sensitivity (type of microbe and its drug sensitivity). The data obtained was analyzed using SPSS v. 21.0. Results: Mean age of the children was 9.12 years, with males comprising 63.4%. Fever and abdominal pain were the most common clinical symptoms. In terms of antibiotic sensitivity, Cefixime and Ceftriaxone were effective in 83.9% and 85.7% of cases, respectively, while Ciprofloxacin showed 81.3% sensitivity. Both Meropenem and Azithromycin were 100% effective. Among the 14 multidrug-resistant cases, Ciprofloxacin had the highest resistance rate (11 cases), while Cefixime and Ceftriaxone were resistant in 9 and 8 cases, respectively. Meropenem and Azithromycin showed no resistance in any case. Conclusion: Enteric fever remains a serious threat to child health, with rising multidrug resistance. While some drugs like Meropenem and Azithromycin are still 100% effective, they must be used carefully to prevent further resistance development.

TNKS1BP1 facilitates ubiquitination of CNOT4 by TRIM21 to promote hepatocellular carcinoma progression and immune evasion

Immune checkpoint inhibitors, particularly PD-1/PD-L1 blockades, have been approved for unresectable hepatocellular carcinoma (HCC). However, high resistance rates still limit their efficacy, highlighting the urgent need to understand the underlying mechanisms and develop strategies for overcoming the resistance. In this study, tankyrasel binding protein 1 (TNKS1BP1) was found to interact with tripartite motif containing 21 (TRIM21) and mediated the ubiquitination of CCR4-NOT transcription complex subunit 4 (CNOT4) at the K239 residue via K48 and K6 linkage, which was essential for its tumorigenesis function. Autophagy and lipid reprogramming were identified as two possible mechanisms underlying the pro-tumor effect of TNKS1BP1. Upregulated TNKS1BP1 inhibited autophagy while induced lipid accumulation by inhibiting the JAK2/STAT3 pathway upon the degradation of CNOT4 in HCC. Importantly, knocking down TNKS1BP1 synergized with anti-PD-L1 treatment by upregulating PD-L1 expression on tumor cells via the JAK2/STAT3 pathway, and remodeling the tumor microenvironment by increasing infiltration of tumor-infiltrating lymphocytes as well as augmenting the effect of cytotoxic T lymphocytes. In conclusion, this study identified TNKS1BP1 as a predictive biomarker for patient prognosis and a promising therapeutic target to overcome anti-PD-L1 resistance in HCC.

Efficacy of epetraborole against Mycobacteroides abscessus in a mouse model of lung infection.

Mycobacteroides abscessus (Mab or Mycobacterium abscessus) is a fast-growing mycobacterium that is ubiquitous in the environment and can cause opportunistic disease in people with lung comorbidity and immunodeficiency. There are no Food and Drug Administration-approved drugs for this disease, and repurposed antibiotics have a poor microbiological response. To address the need for effective new antibiotics, we determined the efficacy of epetraborole (EBO) against three Mab clinical isolates in a mouse model of lung Mab infection. Reduction in lung Mab burden over 4 weeks of treatment was the study end point. EBO was administered orally once daily at doses of 25 and 50 mg/kg, which achieved exposures approximating the once-daily dosing of 250 mg and 500 mg, respectively, in humans. EBO administration led to a gradual reduction in the lung Mab burden. After 4 weeks of treatment, the efficacies of 25 and 50 mg/kg EBO against isolates ATCC 19977 and M9501 were comparable. However, against isolate M9530, 50 mg/kg EBO was more efficacious than 25 mg/kg and comparable with parenteral imipenem, one of the most efficacious antibiotics against Mab. We also undertook a dose-ranging study by evaluating the efficacies of once-daily oral administration of 0.5, 5, 10, 25, and 100 mg/kg EBO against M9501 over 4 weeks. Once-daily oral 100 mg/kg EBO was as effective as twice-daily 100 mg/kg imipenem injection. Our study suggests that EBO could address the unmet need for effective oral treatment options for Mab lung disease, given the high rates of Mab drug resistance and limited tolerable intravenous options.

Comparative Analysis of Methicillin-Resistant Staphylococcus pseudintermedius Prevalence and Resistance Patterns in Canine and Feline Clinical Samples: Insights from a Three-Year Study in Germany.

The emergence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) presents a significant public health concern globally, particularly within veterinary medicine. MRSP's resistance to multiple antibiotics is limiting treatment options and potentially leading to severe infections in companion animals. This study aimed to understand antimicrobial resistance in dogs and cats, focusing on MRSP resistance patterns and its prevalence in Germany. We analyzed results of bacterial diagnostic samples from canines and felines, sourced from a German veterinary diagnostic microbiology laboratory between 2019 and 2021. This dataset included samples from 3491 veterinary practices, covering 33.1% of veterinary practices and clinics in Germany. MRSP rates were detailed by host species, sample types and co-resistance patterns. Analysis of 175,171 bacterial examination results revealed S. pseudintermedius in 44,880 samples, yielding a 25.6% isolation rate. S. pseudintermedius was more prevalent in dogs (35.0%) than cats (3.6%). Methicillin resistance was found in 7.5% of all S. pseudintermedius isolates. MRSP prevalence was higher in feline samples (16.1%, 95% CI 14.4-17.8) compared to canine samples (7.1%, 95% CI 6.8-7.0). S. pseudintermedius showed high resistance rates to ampicillin (cats: 48.6%, dogs: 67.6%) and clindamycin (cats: 37.2%, dogs: 32.7%), while MRSP exhibited high co-resistance to clindamycin (cats: 82.8%, dogs: 85.4%) and sulfamethoxazole + trimethoprim (cats: 66.4%, dogs: 66.2%). Our study revealed distinct resistance patterns of MRSP in cats compared to dogs, highlighting the need for tailored treatment approaches and the importance of antimicrobial resistance surveillance.

Evaluation of Fosfomycin in-vitro susceptibility among gram negative isolates from urine culture in a tertiary care hospital in Lucknow

The rise of bacteria that are Multidrug- resistant or Extended Drug Resistant (MDR or XDR) and the lack of novel antibiotics have wreaked havoc on patient treatment options. Fosfomycin has just recently come to light because of the development of resistance to existing drugs. This study aims to evaluate the Fosfomycin susceptibility of Gram- negative isolates in vitro. A prospective study done in the Department of Microbiology, Integral Institute of Medical Sciences of Research, Lucknow, over a period of six months from April 2023 to September 2023. A total of 1328 urine samples were processed in microbiology lab and after identification of urinary isolates, antibiotic susceptibility testing was performed, and results were interpreted following the Clinical and Laboratory Standards Institute guidelines (CLSI). Fosfomycin sensitivity was tested by the Kirby-Bauer disc diffusion method. 353 of the 1328 processed urine samples showed a growth of pathogens. 184 (52.1%) of the isolates were Gram-negative, while 169 (47.8%) were Gram-positive. Fosfomycin (7%) and Nitrofurantoin (13%) showed lower rates of resistance among these isolates. Relatively higher rates of resistance were observed for Doripenem (17%), Meropenem (17%), Imipenem (18%), Amikacin (18%), Gentamicin (27.9%). Norfloxacin, Aztreonam, Cefepime, Ciprofloxacin and Levofloxacin and Cotrimoxazole showed a high resistance rate of 46.2%, 48.8%, 50%, 60.4%, 61% and 70% respectively. Fosfomycin's low resistance (7%) to the antibiotic indicates that it works well as a urinary antibiotic. Uropathogenic Enterobacteriaceae isolates exhibited an excellent level of in vitro susceptibility to Fosfomycin. These in vitro results highlight the unexplored possibilities of Fosfomycin as a superior therapeutic option for the treatment of UTIs, and it has a good chance of expanding into a safe and effective oral alternative treatment that can be used in inpatient as well as outpatient settings.

Prevalence of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae and Associated Clinical Implications at the University Teaching Hospital of Kigali in Rwanda.

Extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae poses a global problem and complicates therapeutic choices. The paucity of data in resource-poor countries undermines the understanding of the problem's extent, and cases of antimicrobial treatment failure continue to accumulate. This study aimed to determine the prevalence and clinical implications of ESBL-producers at the University Teaching Hospital of Kigali in Rwanda. A 1-year cross-sectional retrospective study was conducted on Escherichia coli and Klebsiella pneumoniae isolated in blood and urine from January 1 to December 31, 2022. In total, 1,283 isolates were recorded. The results showed an overall prevalence of ESBL phenotypes at 300/1,283 (23.4%). Extended spectrum beta-lactamase-positive E. coli was more frequently detected than K. pneumoniae in both urine (20.6% versus 10.1%) and blood (8.8% versus 6.2%). These isolates were 100% resistant to amoxicillin-clavulanic acid, third-generation cephalosporins, piperacillin, sulbactam ampicillin, ampicillin, cefuroxime, and cefoxitin. The least resistance was observed to amikacin (18%), meropenem (10%), and polymyxin B (3%). Hospital stays ranging from 8 to 21 days were the most frequent, and the mortality rate was 10.3% in patients with ESBL cases, which was more than double the general hospital mortality rate in the same period. In conclusion, our findings indicate a high prevalence of ESBL phenotypes, high antibiotic resistance rates, prolonged hospital stays, and an increased mortality rate. These findings suggest the need for continued surveillance, planning appropriate interventions, and caution during empirical therapy.

ANTIMICROBIAL RESISTANCE PATTERNS AMONG BACTERIAL PATHOGENS ISOLATED FROM CLINICAL SAMPLES IN SANA'A HOSPITALS

Background and objectives: Yemen is among the developing nations where antimicrobial resistance (AMR) is posing a danger to public health. AMR can lead to increased morbidity and mortality from treatment failures and a lack of effective therapies. Particularly in the research arena, there is a dearth of knowledge about the antimicrobial resistance patterns of frequently isolated, locally occurring diseases. Therefore, the purpose of this study was to evaluate the diseases' microbiological profiles and resistance trends in Sana'a, Yemen. Methods: In Sana'a, Yemen, a retrospective study was carried out at various governmental and private hospitals between June and September of 2020. Information about antibiotic susceptibilities and cultures was taken from the microbiology department's 2019 files. The data analysis method employed was descriptive statistics. Results: This study includes 4156 pathogen isolates, with 58.2% of the isolates being Gram negative. Of all the isolates, urine (26.1 %, n = 1086) and pus specimens (24.6 %, n = 1025) demonstrated the greatest detection rates. The most often isolated pathogens were S. aureus (35.6%, n=1479), E. coli (29.2%, n=1215), P. aeroginosa (14.1%, n=586), and Klebsiella species (10.7%, n=443). The highest rates of resistance were found for cephalosporins (cefixime 90%, cefadroxil 87.9%, cefepime 72%, and ceftriaxone 70%) and penicillins (carbincillin 87%, amoxacillin 80%, and amoxacillin/clavulanic acid 77%). Gram positive and Gram negative isolates showed minimal resistance to linezolid and vancomycin, with Enterococcus showing higher resistance. Colistin was most effective against Gram negative, while E. coli, Klebseilla, and Proteus showed high resistance. Conclusions: The high rate of resistance discovered in the current study in both Gram-positive and Gram-negative organisms is alarming and highlights the necessity of routinely determining the prevalence of resistance in a given area in order to guide empirical therapy and choose the most effective course of antibiotic treatment. Peer Review History: Received 27 March 2024; Revised 8 May 2024; Accepted 27 June; Available online 15 July 2024 Academic Editor: Prof. Dr. Gorkem Dulger, Duzce University, Turkey, gorkemdulger@yandex.com Average Peer review marks at initial stage: 6.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. Heba M. Abd El-Azim, Damanhour University, Egypt, h_m_abdelazim@hotmail.com Dr. Jennifer Audu-Peter, University of Jos, Nigeria, drambia44@gmail.com

Antimicrobial use, residues and resistance in fish production in Africa: systematic review and meta-analysis

In low- and middle-income countries, data on antimicrobial use (AMU) and antimicrobial resistance (AMR) in aquaculture are scarce. Therefore, summarizing documented data on AMU, antimicrobial residue (AR), and AMR in aquaculture in Africa is key to understanding the risk to public health. Google Scholar, PubMed, African Journals online, and Medline were searched for articles published in English and French following the PRISMA guidelines. A structured search string was used with strict inclusion and exclusion criteria to retrieve and screen the articles. The pooled prevalence and 95% confidence intervals were calculated for each pathogen–antimicrobial pair using random effects models. Among the 113 full-text articles reviewed, 41 met the eligibility criteria. The majority of the articles reported AMR (35; 85.4%), while a few were on AMU (3; 7.3%) and AR (3; 7.3%) in fish. The articles originated from West Africa (23; 56.1%), North Africa (8; 19.7%), and East Africa (7; 17.1%). Concerning the antimicrobial agents used in fish farming, tetracycline was the most common antimicrobial class used, which justified the high prevalence of residues (up to 56.7%) observed in fish. For AMR, a total of 69 antimicrobial agents were tested against 24 types of bacteria isolated. Bacteria were resistant to all classes of antimicrobial agents and exhibited high levels of multidrug resistance. Escherichia coli, Salmonella spp., and Staphylococcus spp. were reported in 16, 10, and 8 studies, respectively, with multidrug resistance rates of 43.1% [95% CI (32.0–55.0)], 40.3% [95% CI (24.1–58.1)] and 31.3% [95% CI (17.5–49.4)], respectively. This review highlights the high multidrug resistance rate of bacteria from aquaculture to commonly used antimicrobial agents, such as tetracycline, ampicillin, cotrimoxazole, gentamicin, and amoxicillin, in Africa. These findings also highlighted the lack of data on AMU and residue in the aquaculture sector, and additional efforts should be made to fill these gaps and mitigate the burden of AMR on public health in Africa.

Epidemiological characteristics and drug resistance of diarrheagenic Escherichia coli infection in diarrhea patients in Shanghai, 2016-2022

Objective: To understand the infection status, epidemiological characteristics and drug resistance of Diarrheagenic Escherichia coli (DEC) in Shanghai and provide evidence for the disease surveillance. Methods: The epidemiological data of diarrhea cases in Shanghai from 2016 to 2022 were collected from Shanghai Diarrhea Comprehensive Surveillance System, and stool samples were collected from the cases for DEC detection. The drug resistance data was obtained from Chinese Pathogen Identification Network. Statistical analysis was conducted by using χ2 and fisher test. Results: In 24 883 diarrhea cases detected during 2016-2022, the DEC positive rate was 9.13% (2 271/24 883), the single DEC positive rate was 8.83% (2 197/24 883) and the mixed DEC positive rate was 0.30% (74/24 883). The main type of DEC was Enterotoxigenic Escherichia coli (ETEC) [4.33% (1 077/24 883)]. The DEC positive rate was highest in people aged ≤5 years 18.48% (22/119). The annual peak of DEC positive rate was observed during July - September [5.91% (1 470/24 883)]. The DEC positive rate were 9.47% (554/5 847) and 9.02% (1 717/19 036) in urban area and in suburbs, respectively, Enteroaggregative Escherichia coli (EAEC) [3.98% (233/5 847)] and ETEC [4.56% (868/19 036)] were mainly detected. From 2016 to 2019, the DEC positive rate was 9.42% (1 821/19 330), while it was 8.10% (450/5 553) from 2020 to 2022, the main DEC types were ETEC (4.87%, 941/19 330) and EAEC (4.70%, 261/5 553). The multi-drug resistance rate was 40.21% (618/1 537). The top three antibiotics with high drug resistance rates were ampicillin [64.74% (995/1 537)], nalidixic acid [58.49% (899/1 537)] and tetracycline [45.09% (693/1 537)]. Conclusions: Compared with 2016- 2019, a decrease in DEC detection rate was observed during 2020-2022, and the main type of DEC detected shifted from ETEC to EAEC. The prevalence of multi-drug resistance was severe. Therefore, it is necessary to further strengthen the surveillance for DEC drug resistance and standardize the use of clinical antibiotics.

Occurrence of multi-carbapenemase-producing Enterobacterales in a tertiary hospital in Madrid (Spain): A new epidemiologic scenario

IntroductionMulti-carbapenemase-producing Enterobacterales (M-CPE) are increasingly described. We characterized the M-CPE isolates prospectively recovered in our hospital (Madrid, Spain) over two years (2021–2022). MethodsWe collected 796 carbapenem resistant Enterobacterales (CRE) from clinical and surveillance samples. Carbapenemase production was confirmed with phenotypic (immunochromatographic, disk diffusion) and molecular (PCR, WGS) techniques. Antimicrobial susceptibility was evaluated by a standard broth microdilution method. Clinical and demographic data were collected. ResultsOverall, 23 M-CPE (10 Klebsiella pneumoniae, 6 Citrobacter freundii complex, 3 Escherichia coli, 2 Klebsiella oxytoca, and 2 Enterobacter hormaechei) isolates were recovered from 17 patients (3% with CPE, 0.26-0.28 cases per 1000 admissions). OXA-48 + KPC-3 (7/23) and KPC-3 + VIM-1 (5/23) were the most frequent carbapenemase combinations. All patients had prior antibiotics exposure, including carbapenems (8/17). High resistance rates to ceftazidime/avibactam (14/23), imipenem/relebactam (16/23) and meropenem/vaborbactam (7/23) were found. Ceftazidime/avibactam + aztreonam combination was synergistic in all metallo-β-lactamase producers. Clonal and non-clonal related isolates were found, particularly in K. pneumoniae (5 ST29, 3 ST147, 3 ST307) and C. freundii (3 ST8, 2 ST125, 1 ST563). NDM-1 + OXA-48 was introduced with the ST147-K. pneumoniae high-risk clone linked to the transfer of a Ukrainian patient. We identified four possible nosocomial clonal transmission events between patients of the same clone with the same combination of carbapenemases (KPC-3 + VIM-1-ST29-K. pneumoniae, NDM-1 + OXA-48-ST147-K. pneumoniae and KPC-2 + VIM-1-ST145-K. oxytoca). Carbapenemase-encoding genes were located on different plasmids, except for VIM-1 + KPC-2-ST145-K. oxytoca. Cross-species transmission and a possible acquisition overtime was found, particularly between K. pneumoniae and E. coli producing OXA-48 + KPC-3. ConclusionM-CPE is an emerging threat in our hospital. Co-production of different carbapenemases, including metallo-β-lactamases, limits therapeutic options and depicts the need to reinforce infection control measures.

Mycoplasma genitalium's Antibiotic Resistance in Sexually Transmitted Infections Clinics in Israel.

To determine the prevalence of antibiotic resistance rate in Mycoplasma genitalium, and distribution of mutations associated with this resistance, among patients that attended sexually transmitted infections (STI) investigation clinics. This cross-sectional study included M. genitalium-positive samples (urine, vaginal, rectal, and pharyngeal swabs) collected from 170 patients attending two STI investigation clinics, which were subjected to macrolide and quinolone resistance mutations analyses. Data regarding patient age, sex, and material/anatomical site of testing were collected. Macrolide-resistance mutations were identified in 48.8% of samples and were more common among males (p < .0001) and in rectal samples (p < .05). A2059C was the most prevalent macrolide-resistance mutation (18.2%). Quinolone resistance was detected in 23% of the samples, with S83I being the most common (17.1%) mutation. Rate of co-resistance to macrolides and quinolones was 21.2%. The high rate of antibiotic resistance found in the current study, especially to macrolides, underscores the importance of antibiotic resistance monitoring in M. genitalium isolates in cases of persistent or recurrent urethritis/cervicitis, in cases of treatment failure and among specific populations. Such surveillance will improve treatment regimens and cure rates.

A Four-Year Trend of Ceftriaxone Resistance and Associated Risk Factors Among Different Clinical Samples in Wad Medani, Sudan: A Cross-Sectional Retrospective Study.

Introduction In sub-Saharan Africa, including Sudan, there is commonly no local data on the bacterial profile or antibiotic resistance pattern. Therefore, to bridge these gaps, this study aimed to evaluate ceftriaxone resistance patterns and associated risk factors among different clinical samples. Methods This study was a laboratory-based, retrospective,cross-sectional study. All clinical specimens were obtained from patients at Wad Medani and examined at the Pathology Center for Diagnosis and Research, Faculty of Medicine, University of Gezira, Sudan, from January 2020 to October 2023. Results Overall, 1784 specimens exhibited bacterial growth over four years. Of these, 1260 (70.6%) were females. Approximately one-third of the 588 (33%) studied patients were aged 30 to 44 years. Of the studied samples, 1108 (62.1%) were urine, and 465 (26.1%) were wound swabs. Staphylococcus aureus(697, 39.1%) and Escherichia coli(656, 36.8%) were the most frequently encountered bacteria. Generally, ceftriaxone resistance has been evaluated in 150 positive culture samples. The overall ceftriaxone resistance rate was 106 (70.7%). The greatest proportion of ceftriaxone resistance was observed in 4/4 (100%) of Klebsiella spp. and 66/82 (80.5%)of E. coli strains. The type of isolate (95% Cl, p-value; 0.006) and type of bacterial stain (95% Cl, p-value0.013) have been significantly associated with ceftriaxone resistance, in which Gram-negative bacteria had a greater resistance rate of 98/132 (74.2%)than Gram-positive bacteria 8/18 (44.4%). Conclusions This study revealed a high rate of ceftriaxone resistance. The most resistant bacteria were Klebsiella spp. and E. coli. The type of isolate and bacterial stain were significantly associated with ceftriaxone resistance. Therefore, hospitals should immediately and significantly modify their antibiotic prescription policy to give doctors a consistent strategy for the rational, safe, and effective administration of antibiotics.

Risk factors for dairy cows mastitis in Algeria, antibiotic resistance and molecular typing of the causative Staphylococcus aureus.

Adoption of a rational management in dairy farms would improve the milk quality and farmers' income. In the current study, we aimed to describe bovine mastitis in 32 dairy herds, identify the main cow- and herd-associated risk factors, and analyze both epidemiological along with molecular characteristics of Staphylococcus aureus infecting udders. Based on Californian Mastitis Test and clinical examination, the prevalence of mastitis in cows was 52.25% (116/222), of which 6.3% was clinical mastitis and 45.94% was subclinical mastitis. Overall, 218 (24.54%) quarters suffered from mastitis, whose 29.81% (65/218) infected with S. aureus. Mastitis was lowest in mid-lactation with OR = 0.371 with 95% confidence interval (CI) of 0.141-0.976, and in cows separated from their calves (OR = 0.164, 95% CI 0.056-0.477) than suckler cows. Similar results were obtained from S. aureus related mastitis. To assess the genetic lineages of S. aureus isolates, we determined clonal complexes (CC) using DNA microarray hybridization profiles and performed spa typing. The strains were assigned to nine clonal complexes, and 19 spa types; with CC97 (44.77%), and CC22 (40.29%) were the most predominant lineages and t223 (40.29%), t7136 (10.44%), t359 (8.95%) and t267 (5.97%) were the most common spa types. A total of 88.05% (n = 59) isolates were resistant to at least one tested antibiotic while only 4.47% were multi-drug resistant strains. Higher rates of resistance were observed for penicillin (86.5%) and tetracycline (14.9%) respectively. Our results show the need for adoption of feasible mastitis program with special emphasis on sub-clinical mastitis and associated risk factors.

Incidence, antimicrobial resistance and mortality of Klebsiella pneumoniae bacteraemia in Shanghai, China, 2018–2022

Background Klebsiella pneumoniae (KP) accounts for high antimicrobial resistance and mortality rates of bloodstream infections (BSIs). Objectives To investigate incidence, antimicrobial resistance and risk factors for mortality of KP BSIs in East China. Methods A retrospective study of patients with KP BSIs was conducted in a tertiary care hospital from 2018 to 2022. Medical records of all hospitalised patients with KP BSIs were reviewed and analysed. The incidence, antimicrobial resistance and mortality of KP BSIs were evaluated. The Kaplan-Meier method was used to plot survival curves and logistic regression was used to analyse risk factors for crude 30-day mortality. Results A total of 379 inpatients with KP BSIs were enrolled. The incidence of patients with KP BSIs was fluctuating between 4.77 and 9.40 per 100,000 patient-days. The crude 30-day mortality rate of these patients was 26.39%. Of the 379 KPisolates, 197 (51.98%) were carbapenem-resistant (CR) and 252 (66.49%) were multidrug-resistant (MDR). All isolates showed the lowest resistance to tigecycline (13.77%) and polymyxin B (14.61%). Cases with MDR/CR isolates had significantly longer length of hospital stay, higher crude 30-day mortality and medical costs than non-MDR/non-CR isolates. Age, CR phenotype, paracentesis, indwelling central venous catheter (CVC), use of carbapenems, tetracyclines, polymyxins B, and irrational empiric treatment were independently associated with crude 30-day mortality. Conclusion MDR/CR KP BSIs are associated with increased mortality, healthcare costs and prolonged hospitalisation. Patients with advanced age, CR phenotype, paracentesis, CVC, exposure to some antibiotics, and irrational empirical antibiotic treatment are at higher mortality risk.

Antimicrobial resistance trends among Klebsiella pneumoniae associated with urinary tract infections in Crete, Greece, 2017-2022.

Klebsiella pneumoniae is one of the most prevalent bacteria causing urinary tract infections (UTIs). Its increasing resistance to a wide array of antibiotics limits available treatment options. This study investigated the characteristics and trends of antimicrobial resistance in K. pneumoniae isolated from UTIs in Crete, Greece, during 2017 and 2022. Among the 11,946 Enterobacteriaceae isolated from urine specimens, a total of 1,771 K. pneumoniae isolates were identified (14.8%), with an isolation frequency secondary to Escherichia coli (66.3%). K. pneumoniae isolates increased over the years, with a peak in the year 2022. Higher resistance rates were detected in ciprofloxacin (41%), trimethoprim/sulfamethoxazole (TMP/SMX) (38.1%) and nitrofurantoin (33.9%). Resistance to ciprofloxacin, amoxicillin/clavulanic acid, tigecycline, and TMP/SMX significantly increased from 33.7%, 24%, 6%, and 33.1%, respectively, over the years 2017-2019, to 47.8%, 34.2%, 14.3% and 42.8%, respectively, over the period 2020-2022. ESBL production and carbapenem resistance were decreased by 2.2% and 3.7%, respectively, over the two three-year periods (2017-2019 and 2020-2022). Among the 278 carbapenem-resistant K.pneumoniae (CRKP) isolates, 164 (59%), 66 (23.7%), 18 (6.5%) and 16 (5.8%) were positive for KPC, NDM, VIM and OXA-48 enzymes, respectively. Only 14 (5%) isolates harboured two carbapenemase genes, namely 10 (3.6%) both blaNDM and blaVIM, and 4 (1.4%) both blaKPC and blaNDM. Females, inpatients and the elderly were more frequently affected by CRKP. The frequency of multidrug-resistant (MDR) and extensively drug-resistant (XDR) isolates were 32.6% and 7.7%, respectively. Continuous surveillance of local microbial prevalence and monitoring of antimicrobial resistance patterns provide critical information to guide the empiric therapy for UTIs and control the spread of MDR bacteria.

Genetic background of aminoglycoside-modifying enzymes in various genetic lineages of clinical aminoglycosides-resistant E. coli and K. pneumoniae isolates in Tunisia.

This study was conducted to evaluate the in vitro activity of clinically relevant aminoglycosides and to determine the prevalence of genes encoding aminoglycoside modifying enzymes (AMEs) and 16S ribosomal RNA (rRNA) methyltransferases among aminoglycoside-resistant E. coli (n=61) and K. pneumoniae (n=44) clinical isolates. Associated resistances to beta-lactams and their bla genes as well as the genetic relatedness of isolates were also investigated. A total of 105 aminoglycoside-resistant E. coli (n=61) and K. pneumoniae (n=44) isolates recovered between March and May 2017 from 100 patients hospitalized in different wards of Charles Nicolle Hospital of Tunis, Tunisia, were studied. Minimal inhibitory concentrations of aminoglycoside compounds were determined by broth microdilution method. Aminoglycosides resistance encoding genes [aph(3´)-Ia, aph(3') IIa, aph(3´)-VIa, ant(2″)-Ia, aac(3)-IIa, aac(3)-IVa, aac(6')-Ib, rmtA, rmtB, rmtC, armA, and npmA] and bla genes were investigated by PCR and sequencing. Genetic relatedness was examined by multilocus sequence typing (MLST) for representative isolates. High rates of aminoglycoside resistance were found: gentamicin (85.7%), tobramycin (87.6%), kanamycin (78.0%), netilmincin (74.3%), and amikcin (18.0%). Most common AME gene was aac(3)-IIa (42%), followed by aac(6')-Ib (36.2%) and aph(3')-VIa (32.4%). The majority of isolates were resistant to beta-lactams and blaCTX-M-15 was the most common ESBL. The blaNDM-1 and blaOXA-48 were also produced by 1 and 23 isolates, respectively. Novel sequence types have been reported among our isolates and high-risk clonal lineages have been detected, such as E. coli ST43 (ST131 in Achtman MLST scheme) and K. pneumoniae (ST11/ST13). The high prevalence of aminoglycoside resistance rates and the diversity of corresponding genes, with diverse β-lactamase enzymes among genetically heterogeneous clinical isolates present a matter of concern.

Drug-Resistant Profiles and Genetic Diversity of Mycobacterium Tuberculosis Revealed by Whole-Genome Sequencing in Hinggan League of Inner Mongolia, China.

Tuberculosis remains a major public health concern in China, with varying prevalence and drug resistance profiles across regions. This study explores the genetic diversity and drug-resistant profiles of MTB strains in Hinggan League, a high TB burden in Inner Mongolia, China. This population-based retrospective study, encompassing all culture-positive TB cases from Jun. 2021 to Jun. 2023 in Hinggan League. Drug resistant profiles and genetic diversity of MTB strains were assessed using phenotypic drug susceptibility testing and whole-genome sequencing. Risk factors associated with drug resistance were analyzed using univariate and multivariate logistic regression models. A total of 211 MTB strains were recovered successfully and included into final analysis. Lineage 2.2.1 (88.6%, 187/211) was the dominant sub-lineage, followed by lineage 4.5 (7.1%, 15/211) and lineage 4.4 (4.3%, 9/211). MTB strains exhibited the highest resistance rates to isoniazid (16.1%, 34/211), followed by rifampicin (10.0, 21/211). In addition, the MTB strains also showed relatively high rates of resistance against new and repurposed anti-TB drugs, with resistant rates of 2.4% (5/211) to delamanid and 1.9% (4/211) to bedaquiline. Overall, 25.6% (54/211) of MTB strains were DR-TB, and 14 MTB strains met the definition of MDR-TB, including 7 strains of simple-MDR-TB, 5 of pre-XDR-TB, and 2 of XDR-TB. Genetic analysis revealed that the dominant mutations of isoniazid-, rifampin-, ethambutol-, levofloxacin-/moxifloxacin-, and ethionamide- resistance were katG_Ser315Thr(46.4%), rpoB_Ser450Leu (47.4%), embB_Met306Val (25.0%), gyrA_Asp94Ala (40.0%), and fabG1_c15t (42.9%), respectively. Previously treated patients (AOR = 2.015, 95% CI: 1.052-4.210) and male patients (AOR = 3.858, 95% CI: 1.416-10.511) were identified as independent risk factors associated with DR-TB. Our study offers crucial insights into the genetic diversity and drug-resistant profiles of TB strains circulating in Hinggan League. These findings are valuable for DR-TB surveillance and for guiding treatment regimens and public health interventions in the region.

Analysis of Differences in Neonatal Sepsis Caused by Streptococcus Agalactiae and Escherichia Coli.

Streptococcus agalactiae (GBS) and Escherichia coli (E. coli) are the main pathogenic bacteria in neonatal sepsis. Therefore, the clinical characteristics, nonspecific indicators, and drug susceptibilities of these two bacteria were studied. In total, 81 and 80 children with sepsis caused by GBS and E. coli infection, respectively, admitted to the neonatal department of our hospital between May 2012 and July 2023, were selected, and the clinical characteris-tics of the two groups were analyzed. Nonspecific indicators and drug sensitivity test results were analyzed retrospectively. Birth weight, tachypnea, groan, tachycardia or bradycardia, and the incidence of complications, such as pneumonia, respiratory failure, and purulent meningitis, were higher in the GBS group than in the E. coli group. The children were born prematurely, and the mother had a premature rupture of membranes. The incidence of jaundice, abdominal distension, atypical clinical manifestations, and complications of necrotizing enterocolitis was lower than of the E. coli group, and the differences were statistically significant (p < 0.05). The WBC, NE#, NE#/LY#, hs-CRP, and PCT of the GBS group were higher than those of the E. coli group, whereas the MPV, D-D, and FDP levels were lower than those in the E. coli group. The differences were all statistically significant (p < 0.05). The 81-bead GBS had high resistance rates against tetracycline (95%), erythromycin (48.8%), and clindamycin (40%), and no strains resistant to vancomycin, linezolid, penicillin, or ampicillin appeared, whereas 80 strains of E. coli were more resistant to penicillin and third-generation cephalosporins, with the higher resistance rates to ampicillin (68.30%), trimethoprim/sulfamethoxazole (53.6%), and ciprofloxacin (42.90%). Resistance rates to carbapenems and aminoglycosides were extremely low. Both GBS and E. coli neonatal sepsis have specific clinical characteristics, especially in terms of clinical manifestations, complications, non-specific indicators, and drug resistance. Early identification is important for clinical diagnosis and treatment.

Prevalence, serotype, antimicrobial susceptibility, contamination factors, and control methods of Salmonella spp. in retail fresh fruits and vegetables: A systematic review and meta-analysis.

This research presents a comprehensive review of Salmonella presence in retail fresh fruits and vegetables from 2010 to 2023, utilizing data from recognized sources such as PubMed, Scopus, and Web of Science. The study incorporates a meta-analysis of prevalence, serovar distribution, antimicrobial susceptibility, and antimicrobial resistance genes (ARGs). Additionally, it scrutinizes the heterogeneous sources across various food categories and geographical regions The findings show a pooled prevalence of 2.90% (95% CI: 0.0180-0.0430), with an increase from 4.63% in 2010 to 5.32% in 2022. Dominant serovars include S. Typhimurium (29.14%, 95% CI: 0.0202-0.6571) and S. Enteritidis (21.06%, 95% CI: 0.0181-0.4872). High resistance rates were noted for antimicrobials like erythromycin (60.70%, 95% CI: 0.0000-1.0000) and amoxicillin (39.92%, 95% CI: 0.0589-0.8020). The most prevalent ARGs were blaTEM (80.23%, 95% CI: 0.5736-0.9692) and parC mutation (66.67%, 95% CI: 0.3213-0.9429). Factors such as pH, water activity, and nutrient content, along with external factors like the quality of irrigation water and prevailing climatic conditions, have significant implications on Salmonella contamination. Nonthermal sterilization technologies, encompassing chlorine dioxide, ozone, and ultraviolet light, are emphasized as efficacious measures to control Salmonella. This review stresses the imperative need to bolster prevention strategies and control measures against Salmonella in retail fresh fruits and vegetables to alleviate related food safety risks.

CuET overcomes regorafenib resistance by inhibiting epithelial-mesenchymal transition through suppression of the ERK pathway in hepatocellular carcinoma

Background and PurposeRegorafenib was approved by the US Food and Drug Administration (FDA) for hepatocellular carcinoma (HCC) patients showing progress on sorafenib treatment. However, there is an inevitably high rate of drug resistance associated with regorafenib, which reduces its effectiveness in clinical treatment. Thus, there is an urgent need to find a potential way to solve the problem of regorafenib resistance. The metabolite of disulfiram complexed with copper, the Diethyldithiocarbamate-copper complex (CuET), has been found to be an effective anticancer drug candidate. In the present study, we aimed to evaluate the effect of CuET on regorafenib resistance in HCC and uncover the associated mechanism. Experimental ApproachRegorafenib-resistant HCC strains were constructed by applying an increasing concentration gradient. This study employed a comprehensive range of methodologies, including the cell counting kit-8 (CCK-8) assay, colony formation assay, cell cycle analysis, wound healing assay, Transwell assay, tumor xenograft model, and immunohistochemical analysis. These methods were utilized to investigate the antitumor activity of CuET, assess the combined effect of regorafenib and CuET, and elucidate the molecular mechanism underlying CuET-mediated regorafenib resistance. Key ResultsThe inhibitory effect of regorafenib on cell survival, proliferation and migration was decreased in regorafenib-resistant MHCC-97H (MHCC-97H/REGO) cells compared with parental cells. CuET demonstrated significant inhibitory effects on cell survival, proliferation, and migration of various HCC cell lines. CuET restored the sensitivity of MHCC-97H/REGO HCC cells to regorafenib in vitro and in vivo. Mechanistically, CuET reverses regorafenib resistance in HCC by suppressing epithelial-mesenchymal transition (EMT) through inhibition of the ERK signaling pathway. Conclusion and ImplicationsTaken together, the results of this study demonstrated that CuET inhibited the activation of the ERK signaling pathway, leading to the suppression of the epithelial-mesenchymal transition (EMT) and subsequently reversing regorafenib resistance in HCC both in vivo and in vitro. This study provides a new idea and potential strategy to improve the treatment of regorafenib-resistant HCC.