Resistance Patterns Research Articles

Molecular characterization and genotype of multi-drug resistant Staphylococcus epidermidis in nasal carriage of young population, Mahasarakham, Thailand.

Staphylococcus epidermidis, a coagulase-negative staphylococcus, is a prevalent skin commensal that has increasingly been recognized as a significant pathogen, particularly in hospital environments, where it is associated with device-related infections. The emergence of multi-drug resistance and its ability to form biofilms complicate the clinical management of infections caused by this organism, posing a growing public health concern. This study aimed to investigate the nasal carriage of S. epidermidis among healthy young individuals and to analyze its antibiotic resistance patterns, resistance genes, and biofilm formation capabilities. Nasal swabs were collected from 40 undergraduate students at Mahasarakham University, Thailand, aged between 20 and 22 years. A total of 38 isolates were confirmed as S. epidermidis through both phenotypic and molecular characterization. Antibiotic susceptibility testing demonstrated resistance to various classes of antimicrobials, including beta-lactams, macrolides, and tetracyclines. Notably, five isolates exhibited methicillin resistance S. epidermidis (MRSE). Resistance genes, such as mecA, ermA, tetM, tetL, and tetK, were identified across the isolates, contributing to the observed resistance profiles. Biofilm formation assays revealed that most isolates displayed weak to moderate biofilm formation, with only one isolate demonstrating strong biofilm-forming capacity. Genetic analysis indicated a significant correlation between biofilm formation and the presence of the icaA gene, which is crucial for biofilm production. This study suggests the necessity for ongoing surveillance of nasal carriage of S. epidermidis to enhance understanding of its role in the dissemination of antimicrobial resistance and biofilm-associated infections, particularly within healthcare settings.

In vivo perturb-seq of cancer and microenvironment cells dissects oncologic drivers and radiotherapy responses in glioblastoma.

Genetic perturbation screens with single-cell readouts have enabled rich phenotyping of gene function and regulatory networks. These approaches have been challenging in vivo, especially in adult disease models such as cancer, which include mixtures of malignant and microenvironment cells. Glioblastoma (GBM) is a fatal cancer, and methods of systematically interrogating gene function and therapeutic targets in vivo, especially in combination with standard of care treatment such as radiotherapy, are lacking. Here, we iteratively develop a multiplex in vivo perturb-seq CRISPRi platform for single-cell genetic screens in cancer and tumor microenvironment cells that leverages intracranial convection enhanced delivery of sgRNA libraries into mouse models of GBM. Our platform enables potent silencing of drivers of in vivo growth and tumor maintenance as well as genes that sensitize GBM to radiotherapy. We find radiotherapy rewires transcriptional responses to genetic perturbations in an in vivo-dependent manner, revealing heterogenous patterns of treatment sensitization or resistance in GBM. Furthermore, we demonstrate targeting of genes that function in the tumor microenvironment, enabling alterations of ligand-receptor interactions between immune and stromal cells following in vivo CRISPRi perturbations that can affect tumor cell phagocytosis. In sum, we demonstrate the utility of multiplexed perturb-seq for in vivo single-cell dissection of adult cancer and normal tissue biology across multiple cell types in the context of therapeutic intervention, a platform with potential for broad application.

Genetic relatedness of diarrheagenic Escherichia coli pathotypes isolated from children under five years of age and food animals in Kisumu County, Kenya

Background: Diarrheal disease remains one of the leading causes of deaths in children below five years of age. The risk factors associated with diarrhea include poor hygiene practices such as open defecation and consumption of contaminated water and food. However, exposure of domestic animal is equally a potential risk factor for diarrhea disease in children. Methodology: We characterized animal-related exposures in a subset of households (n=73) by collecting faecal samples from 150 children with diarrhoea and 100 food animals (30 cattle, 30 chicken, 25 goats and 15 pigs). Escherichia coli was isolated from the faecal samples and biochemically confirmed using conventional microbiological techniques. The deoxyribonucleic acid (DNA) of each E. coli isolate was extracted and amplified by multiplex PCR to identify three diarrheagenic E. coli pathotypes. The amplified products were sequenced, and genetic relatedness of the isolates was determined through phylogenetic analysis. Results: We isolated and identified a total of 32 (12.8%) diarrheagenic E. coli (DEC) from the 250 faecal samples, 26 (17.3%) of which were from the 150 children with diarrhea while 6 (6.0%) were from the 100 food animals (OR=3.285, 95% CI=1.299-8.305, p=0.011). Three DEC pathotypes were confirmed by PCR in 16 DEC strains, with 9 enteroaggregative E. coli (EAEC), 2 enterotoxigenic E. coli (ETEC), 2 enteropathogenic E. coli (EPEC), 1 EAEC/ETEC, 1 EAEC/EPEC and 1 ETEC/EPEC mixed strains. The phylogenetic analysis showed that 6 DEC isolates had genetic similarity ranging between 31% to 90%. Isolates S04 originating from animal and S02 from a child with diarrhoea of the same household were closely related, with 55% similarity. Moreover, isolate S05 from animal origin and S06 of diarrheic child origin were closely related, with similarity degree as high as 82% even though they were not paired. Twenty four of the 26 (92.3%) DEC isolates from diarrhoeic children showed multidrug resistance (MDR) pattern to antibiotics but none of the 6 isolates from food animals was multi-drug resistant. Conclusion: The high degree of genetic relationship between DEC isolate S04 and S02 from animal and human origin indicated the high potency of zoonotic transmission. Further studies investigating animal husbandry practices and zoonotic transmission of DEC are needed.

Antimicrobial resistance pattern and molecular characterization of hypervirulent Klebsiella pneumoniae among hospital-acquired infections in the intensive care unit

Antimicrobial resistance pattern and molecular characterization of hypervirulent Klebsiella pneumoniae among hospital-acquired infections in the intensive care unit

Prevalence and pattern of antibiotic use and resistance among Iraqi patients: a cross-sectional study

Background: According to The Centers for Disease Control and Prevention (CDC) 2019, around 32,000 deaths in addition 2.8 million infections occur annually in the US because of antibiotic-resistant bacteria. Objectives: To determine the prevalence and study pattern of antibiotic use and resistance among Iraqi patients. Methodology: We carried out a cross-sectional study from January 2021 to October 2022 including data of 850 patients at different private and general hospitals, primary health centers, and private clinics. The data was collected during the patient’s admission or visiting time using medical records and mini-interviews. Results: Escherichia coli and Staphylococcus aureus were the most detected pathogens in our sample in 14.5% and 11.29% of the patients respectively. Most patients (87.18%) had taken over-the-counter antibiotics previously. Around 55% of the antibiotics that were tested were resisted among our patients who were included in 2021. This percentage has increased to about 75% of the included patients in 2022. Amoxicillin was the most resistant antibiotic (77%) in our sample while meropenem was the least resistant among the tested antibiotic (5%). Conclusion: Antibiotic resistance is a major public health concern that is often caused by the overuse and misuse of antibiotics, as well as poor infection control practices. Keywords: Antibiotic; resistance; Iraq.

The Spectrum of Pathogens Associated with Infections in African Children with Severe Acute Malnutrition: A Scoping Review.

Understanding the interplay between infections and severe acute malnutrition is critical in attaining good clinical outcomes when managing malnourished children. However, review studies describing the profile of the associated pathogens in the malnourished African paediatric population are sparse in the literature. We aimed to identify the spectrum of pathogens from studies reporting infections in severely malnourished African children, as well as the antibiotic resistance pattern and clinical outcomes. A systematic literature review of the PubMed database was conducted following PRISMA guidelines from January 2001 to June 2024. The search algorithm was ((marasmus) OR (kwashiorkor) OR (severe acute malnutrition) OR (protein energy malnutrition)) AND (Africa). For a more comprehensive retrieval, an additional search algorithm was deployed: ((HIV) OR (tuberculosis)) AND (severe acute malnutrition). We included 60 studies conducted between 2001 and 2024. Most of the studies were from East Africa (n = 45, 75%) and Southern Africa (n = 5, 8.3%). A total of 5845 pathogens were identified comprising 2007 viruses, 2275 bacteria, 1444 parasites, and 119 fungal pathogens. The predominant pathogens were HIV, Mycobacterium tuberculosis, and malaria parasites accounting for 33.8%, 30%, and 24.2% of pathogens identified. Antibiotic susceptibility testing was documented in only three studies. Fatality rates were reported in 45 studies and ranged from 2% to 56% regardless of the category of pathogen. This review affirms the deleterious effect of infections in malnourished patients and suggests a gross underdiagnosis as studies were found from only 17 (31.5%) African countries. Moreover, data on fungal infections in severely malnourished African children were nearly absent despite this population being at risk. Thus, there is an urgent need to prioritize research investigating African children with severe acute malnutrition for fungal infections besides other pathogens and improve the availability of diagnostic tools and the optimized usage of antibiotics through the implementation of antimicrobial stewardship programmes.

Resistance Pattern of Acinetobacter baumannii in Hospitalized Patients

Background: One of the most prevalent bacteria in nosocomial infections is Acinetobacter baumannii. Misuse of antibiotics has resulted in an increase in A. baumannii multidrug-resistant (MDR) strain resistance. To assess the resistant gene pattern of MDR A. baumannii, empirical antibiotic therapy is required. In order to do this, the current study used a genotypic diagnostic technique to assess the resistance gene pattern of MDR A. baumannii that was collected from hospitalized patients. A. baumannii has resistance mechanisms against broad-spectrum antibiotics, including β-lactamases, efflux pumps, and aminoglycosides, altering targets, permeability shifts, and enzyme modifications. Efforts have been made to target plant-derived compounds and a combination of antibiotics and phytocompounds to circumvent resistance mechanisms. Many studies have been conducted on plant extract-synthesised nanoparticles. Additionally, we projected contemporary techniques to investigate insights into the mechanisms of action of antibiotics, such as multi-omics analysis. The data implied that A. baumannii putative antibiotic pathways would result in a different approach to treating A. baumannii infections. One of these resilient pathogens is A. baumannii, which is becoming more common in hospitals, resistant to treatment, and linked to higher death rates. Notwithstanding its clinical importance, little is known about this pathogen's behavior outside of hospitals. Additionally, unknown are its virulence factors. Consequently, our goal in this review is to provide light on the most recent findings about the ecological niches, microbiological characteristics, and antibiotic resistance profiles of A. baumannii. According to recent research, this bacterium is found in an increasing number of environmental niches, such as soils, treatment plants, and rivers.

Characterization of Candida species isolated from clinical specimens: insights into virulence traits, antifungal resistance and molecular profiles

BackgroundCandida species have emerged as a significant cause of opportunistic infections. Alongside the expression of various virulence factors, the rise of antifungal resistance among Candida species presents a considerable clinical challenge.AimThis study aimed to identify different Candida species isolated from clinical specimens, evaluate their antifungal sensitivity patterns, identify key genes regulating virulence mechanisms using multiplex PCR and to assess any correlation between their virulence profiles and antifungal resistance patterns.MethodA total of 100 Candida spp. was isolated from 630 different clinical specimens and identified to the species level. Their antifungal susceptibility was phenotypically evaluated in accordance with CLSI guidelines using the Vitek-2 Compact System. Virulence markers, including biofilm formation capacity, protease production, melanin production, coagulase production and hemolysin production, were also phenotypically detected. The genetic determinants for biofilm formation and extracellular hydrolytic enzymes were assessed using a multiplex PCR assay.ResultsThe prevalence of Candida spp. was 15.9%, with C. albicans (48%) and C. glabrata (16%) being the most common. C. albicans showed the highest virulence, with strong biofilm formation, and high proteinase and melanin production. Multiplex PCR revealed Hlp in 22.0%, Hwp in 80.0%, Als in 56.0%, and Sap genes in 56.0% of isolates. Virulence genes were more common in C. albicans than in non-albicans Candida (NAC). Resistance patterns significantly correlated with virulence profiles, with notable associations between flucytosine resistance and the presence of Hlp and Hwp genes.ConclusionThe significant correlation between virulent markers such as germination, coagulase, hemolysin production and resistance patterns among different Candida isolates is crucial for predicting the severity and outcomes of Candida infections. This understanding aids in guiding tailored treatment strategies.

Enhancing antimicrobial management: A 5–year retrospective analysis of urinary pathogen susceptibility at a tertiary care centre from January 2018 to December 2022

Objective: The study aims to collect data on prevalence and antibiotic susceptibility patterns of uropathogens in a hospital in India, and to analyze any changes that have occurred over the past 5 years. Methods: This retrospective study was conducted over 5 years at Lady Hardinge Medical College & Associated Hospitals, New Delhi. Urine samples from patients who attended outpatient department or were admitted with diagnosis of urinary tract infection (UTI) were included in this study. Samples were cultured and tested to identify bacteria and determine antibiotic susceptibility using the Kirby-Bauer disc diffusion method. Results: A total of number of 151395 urine specimens were collected from January 2018 to December 2022. The prevalence of UTI was 7.5% (11372/151395) with the majority of patients being aged above 40 years (19.3%). The prevalence was higher in females (12.7%) as compared to males (3.2%). Escherichia (E.) coli was the predominant pathogen, accounting for 59.8% of cases, followed by Klebsiella spp. at 18.9%, and Enterococcus spp. at 8.3%. Gram-negative bacteria accounted for 89.5% of the isolates and exhibited good susceptibility to aminoglycosides and piperacillin-tazobactam, but showed resistance to fluoroquinolones. Methicillin-resistant Staphylococcus aureus (MRSA) was present in 35% of Staphylococcus (S.) aureus isolates with high susceptibility to glycopeptides and nitrofurantoin. Conclusions: The data suggest the need for careful selection of empirical therapy due to increasing resistance patterns. The stringent use of antimicrobial agents is pivotal to the control of antimicrobial resistance. Antibiotic susceptibility data contributes to tailoring the antibiotic stewardship programs to local needs.

Antibiotic Resistance Pattern of Lactobacillus reuteri, Lactobacillus salivarius, and Enterococcus hirae Isolated from Gastrointestinal and Respiratory Tract in Commercial Broiler Chickens

Ever since antibiotics were discovered for the treatment of bacterial diseases, an increase in antibiotic-resistant bacteria has been noticed as an economic and public health concern with a high rate of morbidity and mortality. Antibiotic resistance in broiler chickens can be a great threat to public health. This research aimed to screen commercial poultry’s gastrointestinal and respiratory tract bacteria to observe the antibiotic resistance pattern. In this experiment, gastrointestinal tract (GIT) and respiratory tract (RT) bacteria were identified using 16s rRNA gene sequencing from broiler chickens in anaerobic conditions following a bile salt tolerance assay and an antibiotic susceptibility test. Lactobacillus reuteri, Lactobacillus salivarius, and Enterococcus hirae were identified as the isolates. The bacteria found in the gut had a modest degree of bile salt tolerance. The isolates were sensitive to amoxicillin, gentamicin, and streptomycin but resistant to tetracycline, levofloxacin, metronidazole, azithromycin, and erythromycin. This study ensures that the GIT and RT of broiler chicken is a hidden source of the isolated bacteria. A large part of this bacterial population is antibiotic-resistant and reported as a public health concern.

Growth of sulfate-reducing Desulfobacterota and Bacillota at periodic oxygen stress of 50% air-O2 saturation

BackgroundSulfate-reducing bacteria (SRB) are frequently encountered in anoxic-to-oxic transition zones, where they are transiently exposed to microoxic or even oxic conditions on a regular basis. This can be marine tidal sediments, microbial mats, and freshwater wetlands like peatlands. In the latter, a cryptic but highly active sulfur cycle supports their anaerobic activity. Here, we aimed for a better understanding of how SRB responds to periodically fluctuating redox regimes.ResultsTo mimic these fluctuating redox conditions, a bioreactor was inoculated with peat soil supporting cryptic sulfur cycling and consecutively exposed to oxic (one week) and anoxic (four weeks) phases over a period of > 200 days. SRB affiliated to the genus Desulfosporosinus (Bacillota) and the families Syntrophobacteraceae, Desulfomonilaceae, Desulfocapsaceae, and Desulfovibrionaceae (Desulfobacterota) successively established growing populations (up to 2.9% relative abundance) despite weekly periods of oxygen exposures at 133 µM (50% air saturation). Adaptation mechanisms were analyzed by genome-centric metatranscriptomics. Despite a global drop in gene expression during oxic phases, the perpetuation of gene expression for energy metabolism was observed for all SRBs. The transcriptional response pattern for oxygen resistance was differentiated across individual SRBs, indicating different adaptation strategies. Most SRB transcribed differing sets of genes for oxygen consumption, reactive oxygen species detoxification, and repair of oxidized proteins as a response to the periodical redox switch from anoxic to oxic conditions. Noteworthy, a Desulfosporosinus, a Desulfovibrionaceaea, and a Desulfocapsaceaea representative maintained high transcript levels of genes encoding oxygen defense proteins even under anoxic conditions, while representing dominant SRB populations after half a year of bioreactor operation.ConclusionsIn situ-relevant peatland SRB established large populations despite periodic one-week oxygen levels that are one order of magnitude higher than known to be tolerated by pure cultures of SRB. The observed decrease in gene expression regulation may be key to withstand periodically occurring changes in redox regimes in these otherwise strictly anaerobic microorganisms. Our study provides important insights into the stress response of SRB that drives sulfur cycling at oxic-anoxic interphases.1UtHR5dBbf2f8WaGLBYUtHVideo

Effects of the COVID-19 Pandemic on Microbial Keratitis: A 5-Year Comparative Study.

To report the clinical and microbiological profiles of microbial keratitis and its antimicrobial resistance before, during, and after COVID-19. This was a retrospective case-note review of all corneal scrape specimens collected from patients with microbial keratitis from January 2018 to December 2023. Case records were analyzed for demographic characteristics, microbiological diagnosis, and antibiograms. All outcome variables were collected, stratified, and compared between 3 periods: the pre-COVID-19 group (January-December 2019), the COVID-19 group (January 2020-December 2022), and the post-COVID-19 group (January-December 2023). A total of 947 corneal cultures from 947 patients were reviewed. Gram-positive bacteria predominated in all periods, with no significant differences in their distribution. Staphylococcus epidermidis was the most frequently identified organism. Pseudomonas aeruginosa was the most common Gram-negative bacterium, with its incidence significantly lower in the post-COVID period. Fungal infections showed a significant increase in the post-COVID group, with Fusarium sp. being the most common fungus and showing a significant increase in incidence in the post-COVID group. Despite a stable incidence of microbial keratitis, this study highlights a concerning trend in antibiotic resistance. Although some pathogens became less common, those that persisted have become increasingly difficult to treat. Understanding the clinical and microbiological profiles of microbial keratitis and antimicrobial resistance patterns before and after the COVID-19 pandemic is crucial for informed treatment decisions.

The environmental microbial retrieving assessment of cell-processing facilities for cell therapy in a hospital laboratory.

Cell therapy represents a promising treatment modality. A critical component in the production of cell therapy products is maintaining the sterility of cell therapy clean rooms (CTCRs). This study aimed to evaluate the environmental microbial load within CTCRs. We systematically monitored microbial load in CTCRs, following established guidelines. Cultured microbial samples underwent metagenomic sequencing, and alpha and beta diversity analyses, functional annotation, and resistance gene profiling were performed using various bioinformatics tools to assess microbial diversity and function. From November 2023 to January 2024, we collected 42 environmental microbial colony samples from various sources within the CTCR and performed metagenomic sequencing on 39 samples. Alpha diversity analysis revealed no significant differences among surface, settle_plate, and airborne categories, but significant disparities within surface subgroups were revealed. Beta diversity analysis showed notable differences between surface and airborne categories and among surface subgroups. Species distribution analysis identified Bacillus as the predominant genus on surfaces. Functional annotation and resistance gene analysis indicated distinct resistance patterns, with significant variations between subgroups, such as microscopes and transfer windows, and hands and other Grade_B environments. Resistance to hydrogen peroxide was notably higher in the transfer window group. These findings highlight the importance of stringent disinfection protocols and enhanced hand hygiene to maintain sterility in CTCRs. These findings provide valuable insights for implementing effective measures to maintain cleanliness throughout CTCRs. The annotation and study of resistance genes can help rapidly identify methods to control cellular contamination under circumstances of environmental microbial pollution.IMPORTANCEMaintaining the sterility of cell therapy clean rooms (CTCRs) is crucial for the production of safe and effective cell therapy products. Our study systematically evaluated the environmental microbial load within CTCRs, revealing significant microbial diversity and distinct resistance patterns to disinfection methods. These findings underscore the need for stringent disinfection protocols and enhanced hand hygiene practices to ensure CTCR sterility. By identifying key microbial species and their resistance genes, our research provides essential insights into controlling contamination and safeguarding the production environment, ultimately contributing to the reliability and success of cell therapy treatments.

Antibiotic susceptibility of uropathogens: a 3-year retrospective study at Ho Teaching Hospital of Ghana

BackgroundUrinary tract infection (UTI) remains one of the most treated infections in primary healthcare over the last two decades. The infection is treated with antibiotics. However, there have been reported cases of increasing antibiotic resistance globally, limiting the available antibiotics for the treatment of the infection. The study aimed to determine the frequency of bacterial urinary tract infections and their antibiotic resistance pattern in Ho Teaching Hospital of Ghana from 2019–2021.MethodologyData on urine culture and susceptibility testing and patient demographics from 2019–2021 were collected from the microbiology unit archives with a designed Microsoft Excel 2019 form and later exported to IBM SPSS (v26) for statistical analysis on the uropathogens and their antibiotic resistance pattern. P-value < 0.05 was considered statistically significant.ResultsOut of 4806 records, 1005 bacterial isolates were found, with a total prevalence of 20.91%. The most prevalent group of organisms was the Enterobacteriaceae, with E. coli 409 (40.70%) being the most frequent isolate. Of the 772 isolates subjected to amikacin, 48(6.22%) and 6(0.78%) of the Gram-negative and Gram-positive bacterial organisms showed resistance to the antibiotic respectively. 58.96% (148/251) and 3.59% (9/251) of Gram-negatives and Gram-positives were resistant to cotrimoxazole. Out of the 1005 bacterial isolates, 165(16.42%), 161(16.02%) and 2(0.20%) showed multidrug resistance (MDR), extensively-drug resistance (XDR), and pandrug resistance (PDR) respectively.ConclusionThere was a high antibiotic-resistant pattern among the uropathogens reported in this current study, hence, the Standard Treatment Guidelines may need to be updated to reflect the high rates of antibiotic resistance exhibited by most prevalent isolates.

Antimicrobial resistance patterns of bacterial and fungal lower respiratory tract infections among COVID-19 patients and their impact on Mortality

Antimicrobial resistance patterns of bacterial and fungal lower respiratory tract infections among COVID-19 patients and their impact on Mortality

Wastewater-based surveillance of Vibrio cholerae: Molecular insights on biofilm regulatory diguanylate cyclases, virulence factors and antibiotic resistance patterns

Vibrio cholerae is an inherent inhabitant of aquatic ecosystems. The Indian state of West Bengal, especially the Gangetic delta region is the highest cholera affected region and is considered as the hub of Asiatic cholera. V. cholerae were isolated from publicly accessible wastewater of Midnapore, West Bengal, India. Serotyping determined all isolates to be of non-O1/non-O139 serogroups. Moderate biofilm-forming abilities were noticed in most of the isolates (74.7 %) while, high biofilm formation was recorded for only 6.3 % isolates and 19 % of isolates exhibited low/non-biofilm-forming abilities. PCR-based screening of crucial diguanylate cyclases (DGCs) involved in cyclic-di-GMP-mediated biofilm signaling was performed. cdgH and cdgM were the most abundant DGCs among 93.7 % and 91.5 % of isolates, respectively. Other important DGCs, i.e., cdgK, cdgA, cdgL, and vpvC were present in 84 %, 75.5 %, 72 % and 68 % of isolates, respectively. Besides, the non-O1/non-O139 isolates were screened for the occurrence of virulence factor encoding genes. Moreover, among these non-O1/non-O139 isolates, two strains (3.17 %) harbored both ctxA and ctxB genes, which encode the cholera toxin associated with epidemic cholera. ompU was the most prevalent virulence factor, present in 24.8 % of isolates. Other virulence factors like, zot and st were found in 4.7 % and 9.5 % of isolates. Genes encoding tcp and ace were found to be PCR-negative for the isolates. Additionally, crucial virulence factor regulators, toxT, toxR and hapR were found to be PCR-positive in all the isolates. Antibiotic resistance patterns displayed further vulnerabilities with decreased sensitivity towards commonly used antibiotics with multiple antibiotic resistance index ranging between 0.37 and 0.62. The presence of cholera toxin-encoding multi-drug resistant (MDR) V. cholerae strains in environmental settings is alarming. High occurrence of DGCs are considered to encourage further investigations to use them as alternative therapeutic targets against MDR cholera pathogen due to their unique presence in bacterial systems.

Single-cell transcriptomes identify patient-tailored therapies for selective co-inhibition of cancer clones

Intratumoral cellular heterogeneity necessitates multi-targeting therapies for improved clinical benefits in advanced malignancies. However, systematic identification of patient-specific treatments that selectively co-inhibit cancerous cell populations poses a combinatorial challenge, since the number of possible drug-dose combinations vastly exceeds what could be tested in patient cells. Here, we describe a machine learning approach, scTherapy, which leverages single-cell transcriptomic profiles to prioritize multi-targeting treatment options for individual patients with hematological cancers or solid tumors. Patient-specific treatments reveal a wide spectrum of co-inhibitors of multiple biological pathways predicted for primary cells from heterogenous cohorts of patients with acute myeloid leukemia and high-grade serous ovarian carcinoma, each with unique resistance patterns and synergy mechanisms. Experimental validations confirm that 96% of the multi-targeting treatments exhibit selective efficacy or synergy, and 83% demonstrate low toxicity to normal cells, highlighting their potential for therapeutic efficacy and safety. In a pan-cancer analysis across five cancer types, 25% of the predicted treatments are shared among the patients of the same tumor type, while 19% of the treatments are patient-specific. Our approach provides a widely-applicable strategy to identify personalized treatment regimens that selectively co-inhibit malignant cells and avoid inhibition of non-cancerous cells, thereby increasing their likelihood for clinical success.

A-254 Increase of Stenotrophomonas maltophilia Isolates Non-Susceptible to Trimethoprim-Sulfamethoxazole and/or Levofloxacin at Brazilian Hospitals

Abstract Background Stenotrophomonas maltophilia is an emerging multidrug-resistant pathogen that exhibits intrinsic and acquired resistance to a wide variety of antimicrobial agents such as β-lactams, aminoglycosides, quinolone, tetracyclines and disinfectants. In addition to that, the increased resistance to sulfamethoxazole/trimethoprim (SMX/TMP) and Levofloxacin has been reported in the past few years, leading to few therapeutic options. This study aimed to describe the increase of Stenotrophomonas maltophilia clinical isolates recovered from Brazilian hospitals over a 6-year analysis (January 2018 to December 2023). Methods This study design was a retrospective, observational analysis based on microbiological data of emergent BGN-NF isolates detected in several Brazilian tertiary hospitals. The bacterial identification was performed by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF/MS) and the antimicrobial susceptibility profile to trimethoprim-sulfamethoxazole and levofloxacin was determined using disk-diffusion method and epsilometer method, respectively. Only one sample per patient was considered in this analysis. Results During the 6 year period, a total of 1,706 (2018; 221), (2019; 203), (2020; 294), (2021; 276), (2022; 294) and (2023; 418) Stenotrophomonas maltophilia strains were isolated from blood (n=626), respiratory tract (n=365), fluid and secretion (n=235), skin and soft tissue (n=162), urine (n=132), catheter tip (n=112), swab (n=36), bone fragment (n=29) and cerebrospinal fluid (n=9). The major frequency of S. maltophilia isolation occurred among man (52.6%) and the main age range was over 60 years (42.7%), while 0-10 comprised 16.6% of cases. Compared the 6-years period, the resistance rate to trimethoprim-sulfamethoxazole was 2.7%; 5.4%; 5.8%; 2.2%; 5.8%; 7.9% and levofloxacin was 3.6%; 3.4%; 3.1%; 3.3%; 1.7%; 2.9%, respectively. The resistance rate to trimethoprim-sulfamethoxazole and levofloxacin, simultaneously, was 0.23%. Conclusions The incidence rate of S. maltophilia infections has increased significantly, especially in the last year, followed by an increase in the pattern of resistance to trimethoprim-sulfamethoxazole. Regarding trimethoprim-sulfamethoxazole and levofloxacin co-resistance, very low rates were detected in our analysis. Our data point to a scenario wherein the presence of S. maltophilia may have been intensified by the covid-19 pandemic. Regional surveillance reports are extremely important and should be out to understand some aspects of the dynamics of bacterial resistance in both hospital and community settings.

Prevalence and Antimicrobial Susceptibility Patterns of Wound and Pus Bacterial Pathogens at a Tertiary Care Hospital in Central Riyadh, Saudi Arabia

The long history and extensive use of antibiotics have caused resistant bacterial pathogens to emerge, increasing mortality and morbidity. The current study was designed to see the prevalence of aerobic bacterial isolates with their antimicrobial resistance pattern from out- and inpatients requested for wound or pus culture. Retrospective study conducted at a tertiary care hospital in central Riyadh from January 2023 to December 2023. Samples were collected and inoculated onto the appropriate media following standard guidelines. Bacterial pathogens were identified by the Vitek2 compact system. Antimicrobial susceptibility was tested using the Kirby–Bauer disk diffusion method as well as by MIC determination through the Vitek2 compact. A total of 1186 subjects were included in the study with a bacterial isolation rate of 691 (58.3%). Out of these, 155 positive cultures had incomplete information or anaerobic or fungal growth and were excluded from the study. With a slight female predominance (54.9%), the majority of subjects (72.2%) were outpatients, and over half of the isolates (55.2%) were Gram-positive. The most common isolate was Staphylococcus spp. (44.4%), followed by E. coli (13.6%) and P. aeruginosa (12.9%). The highest resistance was reported against penicillin followed by fusidic acid against Gram-positive bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in 40.5% of Staphylococcus aureus (S. aureus) isolates. Amikacin was the most susceptible antibiotic against all Gram-negative isolates. MDR Gram-negative bacteria accounted for 51.9% of wound infection isolates (95% CI: 45.95 to 58.33) while 6.3% (95% CI: 4.39 to 8.86) were XDR (nonsusceptibility to at least one agent in all but two or fewer antimicrobial categories). A high prevalence of bacterial isolates, with S. aureus as the predominant pathogen, showed high rates of multidrug resistance. This highlights the importance of monitoring antibiotic choices for prophylaxis and treatment in the study area.

A-290 Prevalence and Antimicrobial Resistance Pattern of Microorganisms Recovered From Bloodstream Infections From Public Hospitals of São Paulo City, Brazil

Abstract Background Nosocomial Bloodstream Infections (nBSI) are an important cause of morbidity and mortality. Brazilian studies concerning bloodstream infections are important tools that can bring specific issues related to antimicrobial resistance. The objective of this study was to describe the frequency and antimicrobial susceptibility profile of bacterial isolates from BSI in patients admitted to public hospitals in 2022 and 2023. Methods This study was a retrospective analysis from 12 hospitals (January 2022 to December 2023) based on BSI isolates laboratory data detected by the clinical microbiology department of a medical diagnostic laboratory. The identification and susceptibility tests were performed using MALDI-TOF mass spectrometry (Vitek MS) and Vitek®2 systems, according to the manufacture’s recommendations. Coagulase Negative Staphylococci (CoNS) BSI was only considered in the presence of at least two sets of positive blood cultures with the same organism. Results During the period (January 2022 to December 2023) a total of 19,588 microorganisms isolated from BSI were obtained from 12 hospitals. The frequency of organism group was Gram-positive (10,707; 54.7%), Gram-negative (7,874; 40.2%), yeasts (961; 4.9%) and filamentous (46; 0.2%). The order of prevalence (top ten) organisms was CoNS (5,149; 26.3%); Staphylococcus aureus (2,769; 14.1%); Klebsiella spp. (2,355; 12.0%); Escherichia coli (1,301; 6.6%); Acinetobacter spp. (1,293; 6.6%); Streptococcus spp. (1,125; 5.7%); Enterococcus spp. (1,112; 5.7%); Candida spp. (937; 4.8%); Pseudomonas spp. (749; 3.8%) and Proteus spp. (553; 2.8%). Extended spectrum beta-lactamase rates for E. coli and Klebsiella pneumoniae were 31.6% (268/848) and 74.9% (1027/1371), respectively. The resistance to carbapenems was detected mainly in 74.1% (661/892) of Acinetobacter spp. isolates, 60.7% (832/1371) of Klebsiella pneumoniae; 24.5% (114/465) of P. aeruginosa; 9.7% (34/349) of Proteus spp. and 1.4% (12/828) of Escherichia coli. Antimicrobial resistance was observed mainly in 87.2% of CoNS (2831/3247) and 44.5% of S. aureus (743/1669) to methicillin; 22.9% (146/637) of Enterococccus spp. to vancomycin. Conclusions The frequency of Klebsiella spp. isolates from nBSI has progressively increased and effective infection control measures should be taken to prevent them from spreading. The rates of antimicrobials resistance reported for Klebsiella pneumoniae, Acinetobacter spp., CoNS, S. aureus and Enterococcus spp. reinforce the high resistance rates to antimicrobials in São Paulo city.