Methicillin-resistant Research Articles

Threats from the Candida parapsilosis complex: the surge of multidrug resistance and a hotbed for new emerging pathogens

SUMMARY Candida parapsilosis is a common agent of candidiasis that has gained increased attention in recent years, culminating with its recent consideration as a high-priority fungal pathogen by the World Health Organization. Reasons for this classification are the recent surge in incidence and the alarmingly growing rates of drug and multidrug resistance. In addition, several closely related species such as Candida metapsilosis and Candida orthopsilosis may represent recently emerged opportunistic pathogens originated from environmental niches through interspecies hybridization. Here, I review recent research focused on the potential origin and spread of drug resistance and of emerging species in this complex. I will also discuss open questions regarding the possible implications of human activities in these two epidemiological phenomena.

Faecal carriage of extended-spectrum beta-lactamase and carbapenemase-producing enterobacterales among HIV patients at Jimma Medical Center, Southwest Ethiopia.

Enterobacterales infections in immunocompromised individuals are associated with considerable morbidity, mortality, and health care costs. This study aimed to assess the faecal carriage of extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Enterobacterales (CPE) among HIV-infected patients at Jimma Medical Center. A total of 344 stool samples were collected and inoculated on Mac-Conkey and Eosin-Methylene Blue agar and incubated at 35-37°C aerobically. ESBL and carbapenemase production were detected using D68C ESBL/AmpC and D73C CARBA plus (Mast Group, UK). A total of 376 Enterobacterales were isolated. The prevalence of ESBL-PE and CPE carriage rate was 13.3% (50/376) and 4.3% (16/376) respectively. The highest proportion of ESBL producing isolates were found in K. pneumoniae 29.0% (9/31) followed by E. coli 13.4% (39/292). Similarly, K. pneumoniae 12.9% (4/31) was the most common carbapenem-resistant isolate followed by E. coli 3.8% (11/292). Multi-drug resistance was observed in 66.5% (250/376) of the isolates. Prior cephalosporin use (AOR = 7.9; 2.31-27.29), CD4 count (≤ 350 cells/µL) (AOR = 3.8; 1.12-12.9), and comorbidities (AOR = 2.3; 1.24-4.32) were significantly associated with ESBL production. Additionally, cephalosporin use (AOR = 6.34; 1.27-31.66) was significantly associated with the presence of CRE. This study revealed a high prevalence of ESBL-PE and CPE among HIV patients, with K. pneumoniae and E. coli being the dominant isolates. MDR was common, with key risk factors being prior cephalosporin use, low CD4 counts, and comorbidities. These findings emphasize the need for enhanced infection prevention and control, regular screening, and improved antibiotic stewardship to curb the spread of resistant bacteria in immunocompromised individuals.

Bioinspired synthesis of cucurbalsaminones B and C.

Cucurbalsaminones B (1) and C (2) are two abeo-cucurbitane triterpenoids with a unique 5/6/3/6/5-fused ring system and exhibited potent multidrug resistance (MDR)-reversing activity. Herein, we report the first synthesis of these two natural products, both of them were accomplished in 14 steps from commercially available inexpensive resource compound lanosterol. Key features of this synthesis include a biomimetic tandem Wagner-Meerwein type lanostane-to-cucurbitane rearrangement followed by a bioinspired photochemical oxa-di-π-methane (ODPM) rearrangement to complete the skeleton construction and an Eosin Y photoinduced Barton-McCombie deoxygenation to realize the challenging oxidation state adjustment of the sterically hindered C11 position.

Bioinspired synthesis of cucurbalsaminones B and C

Cucurbalsaminones B (1) and C (2) are two abeo‐cucurbitane triterpenoids with a unique 5/6/3/6/5‐fused ring system and exhibited potent multidrug resistance (MDR)‐reversing activity. Herein, we report the first synthesis of these two natural products, both of them were accomplished in 14 steps from commercially available inexpensive resource compound lanosterol. Key features of this synthesis include a biomimetic tandem Wagner‐Meerwein type lanostane‐to‐cucurbitane rearrangement followed by a bioinspired photochemical oxa‐di‐π‐methane (ODPM) rearrangement to complete the skeleton construction and an Eosin Y photoinduced Barton‐McCombie deoxygenation to realize the challenging oxidation state adjustment of the sterically hindered C11 position.

The Crosstalk Between HIV-TB Co-Infection and Associated Resistance in the Indian Population

Extensive research on tuberculosis (TB) and HIV co-infection reveals the diverse prevalence and co-epidemic patterns across populations, necessitating tailored public health strategies. Co-infection is bidirectional; individuals with HIV are more susceptible to TB, and vice versa. Antiretroviral therapy (ART) and antituberculosis treatment (ATT) are critical for managing these conditions, but pose risks due to drug–pathogen and drug–drug interactions, potentially leading to immune reconstitution inflammatory syndrome (IRIS) in patients with HIV/AIDS. IRIS, often triggered by highly active antiretroviral therapy (HAART), can exacerbate HIV progression, increase drug resistance, and deteriorate patients’ quality of life. Approximately one-third of the global population with HIV is also infected with TB, with extensive drug-resistant (XDR) and multidrug-resistant (MDR) strains posing significant challenges. Latent TB infection (LTBI) further complicates the scenario, as it can progress to active TB, particularly in individuals with both conditions. The global and Indian mortality rates for TB-HIV co-infection remain high, emphasizing the need for new strategies. Additionally, unreported cases and inadequate post-treatment monitoring contribute to the high mortality rate, particularly among patients with LTBI. The complexity of managing HIV-TB co-infection, especially with LTBI, underscores the urgency of addressing these challenges to improve the outcomes for the affected populations.

Prevalence of Vancomycin-Resistant Enterococcus spp. Isolates in Southeast Iran, Zahedan

Background: Enterococci are clinically significant, especially in individuals with compromised immune systems, which are recognized as a critical contributor to nosocomial infections. Objectives: This study aimed to determine antibiotic susceptibility profiles and vancomycin-resistance Enterococcus (VRE) isolates in Zahedan, Iran. Methods: A hospital-based cross-sectional study was conducted at Ali Ibne Abi Talib Hospital from March 2019 to February 2022. Clinical samples included urine, blood, abscesses and other body fluids from patients referred to this hospital during the study period. A total of 3000 patients were included in the study, and the Kirby-Bauer method was used to test isolates identified by morphological and biochemical characteristics for antibiotic susceptibility. Data were analyzed using SPSS software version 20. P-values < 0.05 were considered statistically significant. Results: Out of 3000 culture-positive clinical samples comprised of 82 urine, ten blood, one tracheal, two wound, and one pulmonary isolate, were identified as Enterococcus faecalis (69.1%), Enterococcus faecium (7.3%), and Enterococcus spp. (23.6%). Moreover, two-thirds of isolates were multidrug-resistant (MDR). Although 66.7% and 63.9% were sensitive to nitrofurantoin and linezolid, resistance to ciprofloxacin (74.2%) and ampicillin (65.9%) was frequently observed. Nitrofurantoin or linezolid were the only effective antibiotics for UTIs. In addition, 50% of isolates were resistant to vancomycin. Conclusions: Based on the results, a combination of vancomycin/or linezolid and nitrofurantoin for urine infections was effective against Enterococci in this clinical center. Nevertheless, continuous and frequent surveillance for resistance patterns is necessary for the reasonable and evidence-based use of antibiotics.

A peptide targeting outer membrane protein A of Acinetobacter baumannii exhibits antibacterial activity by reducing bacterial pathogenicity.

The World Health Organization has classified multidrug-resistant (MDR) Acinetobacter baumannii as a significant threat to human health, necessitating the urgent discovery of new antibacterial drugs to combat bacterial resistance. Outer membrane protein A of A. baumannii (AbOmpA) is an outer membrane-anchored β-barrel-shaped pore protein that plays a critical role in bacterial adhesion, invasion, and biofilm formation. Therefore, AbOmpA is considered a key virulence factor of A. baumannii. Herein, we screened three phage display peptide libraries targeting AbOmpA and identified several peptides. Among them, P92 (amino acid sequence: QMGFMTSPKHSV) exhibited the highest binding affinity with AbOmpA, with a KD value of 7.84 nM. In vitro studies demonstrated that although P92 did not directly inhibit bacterial growth, it significantly reduced the invasion and adhesion capabilities of multiple clinical isolates of MDR A. baumannii and concentration-dependently inhibited biofilm formation by acting on OmpA. Furthermore, the polymerase chain reaction results confirmed a significant positive correlation between the antibacterial effect of P92 and OmpA expression levels. Encouragingly, P92 also displayed remarkable therapeutic efficacy against A. baumannii infection in various models, including an in vitro cell infection model, a mouse skin infection model, and a mouse sepsis model. These results highlight P92 as a novel and highly effective antimicrobial molecule specifically targeting the virulence factor AbOmpA.

Cefiderocol in Combating Carbapenem-Resistant Acinetobacter baumannii: Action and Resistance

Acinetobacter baumannii (A. baumannii) has emerged as a prominent multidrug-resistant (MDR) pathogen, significantly complicating treatment strategies due to its formidable resistance mechanisms, particularly against carbapenems. Reduced membrane permeability, active antibiotic efflux, and enzymatic hydrolysis via different β-lactamases are the main resistance mechanisms displayed by A. baumannii, and they are all effective against successful treatment approaches. This means that alternate treatment approaches, such as combination therapy that incorporates beta-lactams, β-lactamase inhibitors, and novel antibiotics like cefiderocol, must be investigated immediately. Cefiderocol, a new catechol-substituted siderophore cephalosporin, improves antibacterial activity by allowing for better bacterial membrane penetration. Due to its unique structure, cefiderocol can more efficiently target and destroy resistant bacteria by using iron transport systems. Through its inhibition of peptidoglycan formation through binding to penicillin-binding proteins (PBPs), cefiderocol avoids conventional resistance pathways and induces bacterial cell lysis. The possibility of resistance development due to β-lactamase synthesis and mutations in PBPs, however, emphasizes the need for continued investigation into cefiderocol’s efficacy in combination treatment regimes. Cefiderocol’s siderophore mimic mechanism is especially important in iron-limited conditions because it can use ferric-siderophore transporters to enter cells. Additionally, its passive diffusion through bacterial porins increases its intracellular concentrations, making it a good option for treating carbapenem-resistant A. baumannii, especially in cases of severe infections and ventilator-associated diseases (IVACs). Cefiderocol may reduce MDR infection morbidity and mortality when combined with customized antimicrobial treatments, but further investigation is needed to improve patient outcomes and address A. baumannii resistance issues.

Public health concern of antimicrobial resistance and virulence determinants in E. coli isolates from oysters in Egypt.

The emergence of critical-priority E. coli, carrying a wide array of resistance and virulence factors through food sources, poses a significant challenge to public health. This study aimed to investigate the potential role of oysters sold in Egypt as a source for E. coli, identify their resistance and virulence-associated gene profiles, and assess associated zoonotic risks. A total of 33 pooled fresh oyster samples were obtained from various retail fish markets in Egypt and examined bacteriologically for the presence of E. coli. Antimicrobial resistance was performed by the disk-diffusion method, and the multiple antibiotic resistance index (MAR) was calculated. All isolates were screened for extended-spectrum beta-lactamase (ESBL) (blaTEM, blaSHV, blaCTX-M, and blaOXA-1), plasmid-mediated AmpC blaCMY-2, and carbapenemases (blaKPC, blaNDM, blaVIM, and blaOXA-48) genes by Polymerase chain reaction. Moreover, the presence of virulence-encoding genes was investigated. The virulent MDR strains were clustered using R with the pheatmap package. The prevalence of E. coli was 72.7% (24 out of 33), with 66.7% of the isolates classified as multi-drug resistant, and 75% exhibited MAR values exceeding the 0.2 threshold. Different antimicrobial sensitivity phenotypes and genotype profiles were identified in E. coli isolates. The most prevalent gene detected among all isolates was blaTEM (22/24, 91.7%). Notably, all non-ESBL producers were positive for blaCMY2. Carbapenem-resistant and carbapenem-intermediate strains were carbapenemase producers, with the predominance of the blaKPC gene (11/24, 45.8%). Remarkably, twelve out of sixteen virulence genes were identified, with papC (21/24, 87.5%) and sfa (16/24, 66.7%) genes being the most prevalent. Most isolates carry virulence genes primarily associated with extra-intestinal pathogenic E. coli (ExPEC) (87.5%) and enteropathogenic (EPEC) (70.8%) pathotypes. Four E. coli isolates exhibit cluster patterns. This study provides the first insight into the emergence of virulent MDR E. coli among oysters in Egypt. It underscores the potential role of oysters as a source for disseminating these strains within aquatic ecosystems, presenting a possible threat to public health.

DLK1 Is Associated with Stemness Phenotype in Medullary Thyroid Carcinoma Cell Lines

Medullary thyroid carcinoma (MTC) is a rare and aggressive tumor, often requiring systemic treatment in advanced or metastatic stages, where drug resistance presents a significant challenge. Given the role of cancer stem cells (CSCs) in cancer recurrence and drug resistance, we aimed to identify CSC subpopulations within two MTC cell lines harboring pathogenic variants in the two most common MEN2-associated codons. We analyzed 15 stemness-associated markers, along with well-established thyroid stem cell markers (CD133, CD44, and ALDH1), a novel candidate (DLK1), and multidrug resistance proteins (MRP1 and MRP3). The ability to efflux the fluorescent dye Hoechst 3342 and form spheroids, representing CSC behavior, was also assessed. MZ-CRC-1 cells (p.M918T) displayed higher expressions of canonical markers, DLK1, and MRP proteins than TT cells (p.C634W). MZ-CRC-1 cells also formed more spheroids and showed less dye accumulation (p < 0.0001). Finally, we observed that DLK1+ cells (those expressing DLK1) in both cell lines exhibited significantly higher levels of stemness markers compared to DLK1− cells (those lacking DLK1 expression). These findings underscore DLK1’s role in enhancing the stemness phenotype, providing valuable insights into MTC progression and resistance and suggesting potential therapeutic implications.

HPRT1: a preliminary investigation on its involvement in nasopharyngeal carcinoma.

Accumulating evidences have stressed the association between hypoxanthine phosphoribosyl transferase 1 (HPRT1) overexpression and the poor prognosis of various cancers. Our study, herein, preliminarily investigates the involvement of HPRT1 in nasopharyngeal carcinoma (NPC). Data from TCGA were applied to read HPRT1 expression in diverse cancers including NPC and to predict the prognosis of NPC patients. The total RNA and protein from NPC cells and nasopharyngeal epithelial cells NP460 were extracted to quantify HPRT1 expression. Following the completion of transfection, the proliferation and migration of NPC cells were determined employing MTT, colony formation and western blot assay (the quantification on expressions of protein related to proliferation and migration). HPRT1 was differentially expressed in diverse cancers yet particularly highly expressed in NPC, and high HPRT1 expression was related to the poor prognosis of NPC patients. Also, HPRT1 expression was higher in NPC cells and its silencing diminished the viability and proliferation of NPC cells and reduced the expressions of CyclinD1, CyclinE, Multidrug Resistance Protein 1 (MDR1), matrix metalloproteinase (MMP)-2, and MMP-9. This study preliminarily explored the involvement of HPRT1 in NPC based on some cellular assays in vitro, which may provide evidence for investigating the specific mechanism underlying the effects of HPRT1 in cancers.

Characterization of Extended Spectrum Beta-lactamase Uropathogens Isolated from Refugees with Urinary Tract Infections in Nakivale Refugee Settlement Camp, Southwestern Uganda

The World Health Organization estimates one in four individuals has had at least one urinary tract infection (UTI) episode requiring treatment with an antimicrobial agent. At Nakivale refugee camp, the overwhelming number of refugees often associated with poor living conditions predispose the refugees to urinary tract infections. This study determined the prevalence of UTIs, the antimicrobial susceptibility pattern of the isolated bacterial pathogens, the prevalence of Extended-Spectrum Beta-Lactamase (ESBL) bacteria, and the molecular characterization of genes encoding ESBLs among refugees in the Nakivale refugee settlement. This was a cross-sectional study that involved 216 outpatients who visited Nakivale Health Centre III between July and September 2020. The urine samples were received and examined at the microbiology laboratory of Mbarara University of Science and Technology. The urine samples were cultured and identified. Antibiotic susceptibility was carried out following CLSI recommended guidelines while the presence of genes encoding ESBL was detected using conventional PCR amplification. The prevalence of UTI was 24.1% (52/216). Staphylococcus aureus was the most prevalent causative agent, accounting for 22/52 (42.31%) of total isolates, followed by Escherichia coli 21/52(40.38%). Multidrug-resistant isolates accounted for 71.15% (37/52). A total of twenty-one isolates (70.0%) were extended spectrum beta-lactamase producing bacteria. The most prevalent genes were TEM beta-lactamase (blaTEM) and CTX-M beta-lactamase (blaCTX-M). The prevalence of UTI among refugees in the Nakivale settlement was high which calls for continuous epidemiological surveys to determine the prevalence of multi-drug resistance uropathogens including ESBL-producing organisms across refugee camps in Uganda.

Role of ABCC5 in cancer drug resistance and its potential as a therapeutic target

Over 90% of treatment failures in cancer therapy can be attributed to multidrug resistance (MDR), which can develop intracellularly or through various routes. Numerous pathways contribute to treatment resistance in cancer, but one of the most significant pathways is intracellular drug efflux and reduced drug concentrations within cells, which are controlled by overexpressed drug efflux pumps. As a member of the family of ABC transporter proteins, ABCC5 (ATP Binding Cassette Subfamily C Member 5) reduces the intracellular concentration of a drug and its subsequent effectiveness using an ATP-dependent method to pump the drug out of the cell. Numerous studies have demonstrated that ABCC5 is strongly linked to both poor prognosis and poor treatment response. In addition, elevated ABCC5 expression is noted in a wide variety of malignancies. Given that ABCC5 is regulated by several pathways in a broad range of cancer types, it is a prospective target for cancer treatment. This review examined the expression, structure, function, and role of ABCC5 in various cancer types.

Molecular Characterization of Multidrug-Resistant and Hypervirulent New Delhi Metallo-Beta-Lactamase Klebsiella pneumoniae in Lazio, Italy: A Five-Year Retrospective Study

Background/Objectives: Antimicrobial resistance represents a challenge to public health systems because of the array of resistance and virulence mechanisms that lead to treatment failure and increased mortality rates. Although for years the main driver of carbapenem resistance in Italy has been the Klebsiella pneumoniae KPC carbapenemase, recent years have seen an increase in VIM and NDM metallo-beta-lactamases (MBLs). We conducted a five-year survey of New Delhi Metallo-beta-Lactamase (NDM)-producing Klebsiella pneumoniae (NDM-Kpn) clinical isolates from the Lazio region, Italy; the study aimed to elucidate the molecular mechanisms underpinning their resistant and virulent phenotype. Methods: Antimicrobial susceptibility was evaluated by automated systems and broth microdilution. In silico analysis of acquired resistance and virulence genes was performed using whole-genome sequencing (WGS), molecular typing through MLST, and core genome multi-locus sequence typing (cgMLST). Conclusions: A total of 126 clinical NDM-Kpn isolates were collected from 19 distinct hospitals in the Lazio region. Molecular analysis highlighted the existence of NDM-1 (108/126) and NDM-5 (18/126) variants, 18 Sequence Types (STs), and 15 Cluster Types (CTs). Notably, 31/126 isolates displayed a virulence score of 4, carrying ybt, ICEKp, iuc, and rmp genes. This study identified a variety of NDM-Kpn STs, mainly carrying the blaNDM-1 gene, with a significant number linked to high-risk clones. Of these isolates, 24.6% showed high-level resistance and virulence, emphasizing the risk of the spread of strains that combine multi-drug-resistance (MDR) and virulence. Proactive surveillance and international collaborations are needed to prevent the spread of high-risk clones, as well as further research into new antimicrobial agents to fight antibiotic resistance.

Genomic diversity of Campylobacter jejuni and Campylobacter coli isolates recovered from human and poultry in Australia and New Zealand, 2017 to 2019.

We used genomic and epidemiological data to assess and compare the population structure and origins of Campylobacter, a major foodborne pathogen, in two neighbouring countries with strong trade and cultural links, similar poultry production systems and frequent movement of people and food products. The most common sequence types (STs) differed between Australia and New Zealand, with many unique to each country. Over half of all STs were represented by a single isolate. Multidrug-resistant (MDR) genotypes were detected in 0.8% of all samples, with no MDR isolates detected in poultry. Quinolone and tetracycline resistant ST6964 was prevalent in New Zealand (10.6% of C. jejuni). Closely related isolates suggested some similar food sources or contacts. We have shown that there is little genetic overlap in human and poultry STs of Campylobacter between the countries, which highlights that this common foodborne pathogen has domestic origins in Australia and New Zealand.

Nanoclay Mediated Two-Pronged Strategy for Infected-Wound Healing.

Photothermal therapy (PTT) is an efficient way to combat bacterial infections and circumvent multidrug resistance. However, balancing efficacious bacterial killing and minimizing damage to the surrounding normal tissues remain a great challenge. Herein, a highly cooperative Prussian blue/kaolinite (PB/Kaol) hybrid nanosystem is constructed for antibacterial therapy to accelerate the healing of infected wounds. After hybridization with Kaol, the prepared PB/Kaol forms interfacial Al-O-Fe bonds, a fast charge transfer channel from Kaol to PB, which contributes to the enhanced photothermal effect of PB/Kaol. Additionally, the hydroxyl and Lewis acid-base sites of the Kaol surface could promote the adhesion of PB/Kaol to bacteria, thereby ensuring that as much hyperthermia as possible is focused on the bacteria and minimizing damage to the surrounding healthy tissues. Furthermore, PB/Kaol inherits the anti-inflammatory and hemostasis functions of PB and Kaol, resulting in the rapid healing of infected wounds.

Metagenomics reveals the divergence of gut microbiome composition and function in two common pika species (Ochotona curzoniae, Ochotona daurica) in China.

Gut microbiome plays crucial roles in animal adaptation and evolution. However, research on adaptation and evolution of small wild high-altitude mammals from the perspective of gut microbiome is still limited. In this study, we compared difference in intestinal microbiota composition and function in Plateau pikas (Ochotona curzoniae) and Daurian pikas (Ochotona daurica) using metagenomic sequencing. Our results showed that microbial community structure had distinct differences in different pika species. Prevotella, Methanosarcina, Rhizophagus and Podoviridae were abundant bacteria, archaea, eukaryotes and viruses in Plateau pikas, respectively. However, Prevotella, Methanosarcina, Ustilago and Retroviridae were dominated in Daurian pikas. Functional pathways related to carbohydrate metabolism that refer to utilization of pectin, hemicellulose and debranching enzymes were abundant in Plateau pikas, while the function for degradation of chitin, lignin and cellulose was more concentrated in Daurian pikas. Pika gut had abundant multidrug resistance genes, followed by glycopeptide and beta-lactamase resistance genes, as well as high-risk ARGs, such as mepA, tetM and bacA. Escherichia coli and Klebsiella pneumoniae may be potential hosts of mepA. This research provided new insights for adaptation and evolution of wild animals from perspective of gut microbiome, and broadened our understanding of high-risk ARGs and potential pathogens of wild animals.

Whole-Genome Sequencing Reveals the Population Structure and Genetic Diversity of Salmonella Typhimurium ST34 and ST19 Lineages.

Salmonella Typhimurium is an invasive gastrointestinal pathogen for both humans and animals. To investigate the genetic framework and diversity of S. Typhimurium, a total of 194 S. Typhimurium isolates were collected from patients in a tertiary hospital between 2020 and 2021. Antimicrobial susceptibility testing was used to confirm the resistance phenotype. Whole-genome sequencing and bioinformatics analysis were performed to determine the sequence type, phylogenetic relationships, resistance gene profiles, Salmonella pathogenicity island (SPI) and the diversity of the core and pan genome. The result showed that 57.22% of S. Typhimurium isolates were multidrug resistant and resistance of total isolates to the first-line drug ciprofloxacin was identified in 60.82%. The population structure of S. Typhimurium was categorized into three lineages: ST19 (20.10%, 39/194), ST34-1 (47.42%, 92/194) and ST34-2 (40.65%, 63/194), with the population size exhibiting increasing trends. All lineages harbored variety of fimbrial operons, prophages, SPIs and effectors that contributed to the virulence and long-term infections of S. Typhimurium. Importantly, ST34-1 lineage might potentially be more invasive due to the possession of SPI1-effector gene sopE which was essential for the proliferation, internalization and intracellular presence of S. Typhimurium in hosts. Multiple antimicrobial resistance genes were characteristically distributed across three lineages, especially carbapenem genes only detected in ST34-1&2 lineages. The distinct functional categories of pan genome among three lineages were observed in metabolism, signaling and gene information processing. This study provides a theoretical foundation for the evolved adaptation and genetic diversity of S. Typhimurium ST19 and ST34, among which ST34 lineages with multidrug resistance and potential hypervirulence need to pay more attention to epidemiological surveillance.

Longitudinal genomic surveillance of a UK intensive care unit shows a lack of patient colonisation by multi-drug-resistant Gram-negative bacterial pathogens.

Vulnerable patients in an intensive care unit (ICU) setting are at high risk of infection from bacteria including gut-colonising Escherichia coli and Klebsiella species. Complex ICU procedures often depend on successful antimicrobial treatment, underscoring the importance of understanding the extent of patient colonisation by multi-drug-resistant organisms (MDROs) in large UK ICUs. Previous work on ICUs globally uncovered high rates of colonisation by transmission of MDROs, but the situation in UK ICUs is less understood. Here, we investigated the diversity and antibiotic resistance gene (ARG) carriage of bacteria present in one of the largest UK ICUs at the Queen Elizabeth Hospital Birmingham (QEHB), focusing primarily on E. coli as both a widespread commensal and a globally disseminated multi-drug-resistant pathogen. Samples were taken during highly restrictive coronavirus disease 2019 (COVID-19) control measures from May to December 2021. Whole-genome and metagenomic sequencing were used to detect and report strain-level colonisation of patients, focusing on E. coli sequence types (STs), their colonisation dynamics and antimicrobial resistance gene carriage. We found a lack of multi-drug resistance (MDR) in the QEHB. Only one carbapenemase-producing organism was isolated, a Citrobacter carrying bla KPC-2. There was no evidence supporting the spread of this strain, and there was little evidence overall of nosocomial acquisition or circulation of colonising E. coli. Whilst 22 different E. coli STs were identified, only 1 strain of the pandemic ST131 lineage was isolated. This ST131 strain was non-MDR and was found to be a clade A strain, associated with low levels of antibiotic resistance. Overall, the QEHB ICU had very low levels of pandemic or MDR strains, a result that may be influenced in part by the strict COVID-19 control measures in place at the time. Employing some of these infection prevention and control measures where reasonable in all ICUs might therefore assist in maintaining low levels of nosocomial MDR.

Bacterial isolates and antibiotic sensitivity in canine bacterial keratitis in Korea.

To analyze bacterial isolates associated with canine bacterial keratitis and their antibiotic susceptibility patterns in Korea, focusing on multidrug resistance (MDR) and identifying effective antibiotic combinations for clinical treatment. A total of 146 dogs diagnosed with suspected bacterial keratitis between October 2022 and October 2023 in Korea, with 157 eye samples collected for analysis. Eye samples were cultured to isolate bacteria, and antibiotic susceptibility testing was performed using the minimum inhibitory concentration (MIC) method. Bacterial identification was conducted using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF). The study assessed the efficacy of individual antibiotics and combination therapies. Bacteria were isolated in 55.4% of the samples. The most common genera were Staphylococcus species (48.5%, 48/99), Streptococcus species (13.1%, 13/99), Pseudomonas species (9.1%, 9/99), and Escherichia coli (9.1%, 9/99). Amikacin (84.8%) showed the highest antibiotic susceptibility, while doxycycline exhibited the lowest (17.2%). The most effective antibiotic combinations were amikacin-moxifloxacin (93%). MDR isolates accounted for 52.5% (52/99) of the total bacterial samples. Staphylococcus species were the most common isolates, with 52.5% showing MDR, underscoring the need to curb antibiotic misuse. While antibiotics like amikacin demonstrated high susceptibility rates, their use should be reserved for resistant infections to prevent further resistance development. Rather than focusing solely on finding effective combinations of antibiotics, it is crucial to consider alternative treatment strategies that offer more sustainable solutions. Rather than relying on antibiotic combinations, attention should shift to sustainable alternatives to treat bacterial keratitis and reduce antibiotic dependence in clinical practice.