Vancomycin-resistant Enterococci Research Articles

Synthesis and Biological Evaluation of Novel Oxazolidinone Derivatives Containing Dithiocarbamate Moiety as Antibacterial Agents

Background: In this article, a series of novel oxazolidinone derivatives containing dithiocarbamate moieties have been designed and synthesized. Methods: Their antibacterial activities were measured against Staphylococcus aureus, vancomycin-resistant Enterococcus faecium (VREF), linezolid-resistant Enterococcus faecalis (LREF) and Streptococcus agalactiae (GBS) by minimal inhibitory concentration (MIC) assays. Results: Dithiocarbamates were found conducive to the maintenance of antibacterial activity. Most of them exhibited potent activity against Gram-positive pathogens comparable to linezolid. The most promising compound A8 showed remarkable antibacterial activity against S.aureus, VREF, LREF, and GBS pathogens with MIC values between 0.25 and 1 μg/mL, which might be a promising drug candidate for further investigation. Conclusion: A series of novel oxazolidinone derivatives containing dithiocarbamate moieties might be promising drug candidates for further investigation.

Bosutinib Stimulates Macrophage Survival, Phagocytosis, and Intracellular Killing of Bacteria.

Host-acting compounds are emerging as potential alternatives to combating antibiotic resistance. Here, we show that bosutinib, an FDA-approved chemotherapeutic for treating chronic myelogenous leukemia, does not possess any antibiotic activity but enhances macrophage responses to bacterial infection. In vitro, bosutinib stimulates murine and human macrophages to kill bacteria more effectively. In a murine wound infection with vancomycin-resistant Enterococcus faecalis, a single intraperitoneal bosutinib injection or multiple topical applications on the wound reduce the bacterial load by approximately 10-fold, which is abolished by macrophage depletion. Mechanistically, bosutinib stimulates macrophage phagocytosis of bacteria by upregulating surface expression of bacterial uptake markers Dectin-1 and CD14 and promoting actin remodeling. Bosutinib also stimulates bacterial killing by elevating the intracellular levels of reactive oxygen species. Moreover, bosutinib drives NF-κB activation, which protects infected macrophages from dying. Other Src kinase inhibitors such as DMAT and tirbanibulin also upregulate expression of bacterial uptake markers in macrophages and enhance intracellular bacterial killing. Finally, cotreatment with bosutinib and mitoxantrone, another chemotherapeutic in clinical use, results in an additive effect on bacterial clearance in vitro and in vivo. These results show that bosutinib stimulates macrophage clearance of bacterial infections through multiple mechanisms and could be used to boost the host innate immunity to combat drug-resistant bacterial infections.

The virtue of training: extending phage host spectra against vancomycin-resistant Enterococcus faecium strains using the Appelmans method.

Phage therapy has (re)emerged as a serious possibility for combating multidrug-resistant bacterial infections, including those caused by vancomycin-resistant Enterococcus faecium strains. These opportunistic pathogens belong to a specific clonal complex 17, against which relatively few phages have been screened. We isolated a collection of 21 virulent phages growing on these vancomycin-resistant isolates. Each of these phages harbored a typical narrow plaquing host range, lysing at most 5 strains and covering together 10 strains of our panel of 14 clinical isolates. To enlarge the host spectrum of our phages, the Appelmans protocol was used. We mixed four out of our most complementary phages in a cocktail that we iteratively grew on eight naive strains from our panel, of which six were initially refractory to at least three of the combined phages. Fifteen successive passages permitted to significantly improve the lytic activity of the cocktail, from which phages with extended host ranges within the E. faecium species could be isolated. A single evolved phage able to kill up to 10 of the 14 initial E. faecium strains was obtained, and it barely infected nearby species. All evolved phages had acquired point mutations or a recombination event in the tail fiber genetic region, suggesting these genes might have driven phage evolution by contributing to their extended host spectra.

Phage-specific immunity impairs efficacy of bacteriophage targeting Vancomycin Resistant Enterococcus in a murine model

Bacteriophage therapy is a promising approach to address antimicrobial infections though questions remain regarding the impact of the immune response on clinical effectiveness. Here, we develop a mouse model to assess phage treatment using a cocktail of five phages from the Myoviridae and Siphoviridae families that target Vancomycin-Resistant Enterococcus gut colonization. Phage treatment significantly reduces fecal bacterial loads of Vancomycin-Resistant Enterococcus. We also characterize immune responses elicited following administration of the phage cocktail. While minimal innate responses are observed after phage administration, two rounds of treatment induces phage-specific neutralizing antibodies and accelerate phage clearance from tissues. Interestingly, the myophages in our cocktail induce a more robust neutralizing antibody response than the siphophages. This anti-phage immunity reduces the effectiveness of the phage cocktail in our murine model. Collectively, this study shows phage-specific immune responses may be an important consideration in the development of phage cocktails for therapeutic use.

Investigation of the mutagenic, cytotoxic and antimicrobial effect of bikaverin mycotoxin

Bikaverin is a reddish pigment produced by different fungi species (Mycogone jaapii, Verticillium agaricinum, Beauveria bassiana, Paecilomyces fumosoroseus, Polyporus sulphureus), mainly of the Fusarium genus. Due to its pigment feature, bikaverin can be used as a dye in various fields in the industry. However, it is extremely important to study the mutagenic/genotoxic effects, cytotoxic effects and antimicrobial properties of bikaverin for application of industrial areas. In the study, the mutagenic, cytotoxic and antimicrobial effects of bikaverin were investigated. The mutagenic effect of bikaverin was studied with the Ames test. Salmonella typhimurium TA97a, TA98, TA100, TA102 and TA1535 strains were used in the test. Five different doses of bikaverin (0.075, 0.1, 0.2, 0.3 and 0.5 μg/plate) were tested against strains. It was determined that there was no mutagenic effect of bikaverin. The cytotoxicity of bikaverin was evaluated by MTT test on L929 fibroblast cell line. Bikaverin demonstrated no cytotoxic effect on L929 fibroblast cell line, according to cell viability calculations that showed >73% for all concentrations (1, 0.5, 0.4, 0.3, 0.2, 0.1, 0.075, 0.05, 0.025, 0.01, 0.005 and 0.001 μg/mL) examined. Bikaverin's IC50 value was determined to be 1.79±0.51 g/mL. The antimicrobial activity of the bikaverin was evaluated by using the microdilution method. Bikaverin was found to have antimicrobial effects on Methicillin resistant Staphylococcus aureus, Vancomycin resistant Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans and Candida krusei, as MIC values ranged from 1.25 -5 µg/ mL.

Trinitroglycerin-loaded chitosan nanogels: Shedding light on cytotoxicity, antioxidativity, and antibacterial activities

Aim and backgroundTrinitroglycerin (TNG) is a remarkable NO-releasing agent. Here, we synthesized TNG based on chitosan Nanogels (Ngs) for ameliorating complications associated with high-dose TNG administration. MethodTNG-Ngs fabricated through ionic-gelation technique. Fourier-transformed infrared (FT-IR), zeta-potential, dynamic light scattering (DLS), and electron microscopy techniques evaluated the physicochemical properties of TNG-Ngs. MTT was used to assess the biocompatibility of TNG-Ngs, as the antioxidative properties were determined via lactate dehydrogenase (LDH), reactive oxygen species (ROS), and lipid peroxide (LPO) assays. The antibacterial activity was evaluated against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE). ResultsPhysicochemical characterization reveals that TNG-Ngs with size diameter (96.2 ± 29 nm), polydispersity index (PDI, 0.732), and negative zeta potential (−1.1 mv) were fabricated. The encapsulation efficacy (EE) and loading capacity (LC) were obtained at 71.1 % and 2.3 %, respectively, with no considerable effect on particle size and morphology. The cytotoxicity assay demonstrated that HepG2 cells exposed to TNG-Ngs showed relative cell viability (RCV) of >80 % for 70 μg/ml compared to the TNG-free drug at the same concentration (P < 0.05). TNG-Ngs showed significant differences with the TNG-free drug for LDH, LPO, and ROS formation at the same concentration (P < 0.001). The antibacterial activity of the TNG-Ngs against S. aureus, E. coli, VRE, and MRSA was higher than the TNG-free drug and Ngs (P < 0.05). ConclusionTNG-Ngs with enhanced antibacterial and antioxidative activity and no obvious cytotoxicity might be afforded as novel nanoformulation for promoting NO-dependent diseases.

Comparison of Daily versus Admission and Discharge Surveillance Cultures for Multidrug-Resistant Organism Detection in an Intensive Care Unit.

Admission and discharge screening of patients for asymptomatic gut colonization with multidrug-resistant organisms (MDROs) is a traditional approach to active surveillance, but its sensitivity for detecting colonization is uncertain. Daily rectal or fecal swab samples and clinical data were collected over 12 months from patients in one 25-bed intensive care unit (ICU) in Chicago, IL USA and tested for the following multidrug-resistant organisms (MDROs): vancomycin-resistant enterococci (VRE); third-generation cephalosporin-resistant Enterobacterales, including extended-spectrum β-lactamase-producing Enterobacterales (ESBL); and carbapenem-resistant Enterobacterales (CRE). MDRO detection by (1) admission/discharge surveillance cultures or (2) clinical cultures were compared to daily surveillance cultures. Samples underwent 16S rRNA gene sequencing to measure the relative abundance of operational taxonomic units (OTUs) corresponding to each MDRO. Compared with daily surveillance cultures, admission/discharge cultures detected 91% of prevalent MDRO colonization and 63% of incident MDRO colonization among medical ICU patients. Only a minority (7%) of MDRO carriers were identified by clinical cultures. Higher relative abundance of MDRO-associated OTUs and specific antibiotic exposures were independently associated with higher probability of MDRO detection by culture. Admission and discharge surveillance cultures underestimated MDRO acquisitions in an ICU. These limitations should be considered when designing sampling strategies for epidemiologic studies that use culture-based surveillance.

Multidrug-resistant organism bloodstream infection and hospital acquisition among inpatients in three tertiary Greek hospitals during the COVID-19 era.

From 2019 (pre-COVID-19) to 2022 (COVID-19 years), three tertiary Greek hospitals monitored MDRO bloodstream infection (BSI) and hospital acquisition relying on laboratory data. Surveillance covered carbapenem-resistant Enterobacterales (CRE), Acinetobacter baumannii (CRAB), Pseudomonas aeruginosa (CRPA), vancomycin-resistant enterococci (VRE), and methicillin-resistant Staphylococcus aureus (MRSA), in intensive care units (ICUs) and non-ICUs. Non-ICUs experienced significant increases in CRE, CRAB and VRE during the pandemic. In ICUs, CRE increased in 2021, CRAB in 2020 and 2021, and VRE in 2021 and 2022. KPC predominated among CRE. MDRO BSI and hospital acquisition incidence rates increased, driven by CRE and CRAB.

A simple solid media assay for detection of synergy between bacteriophages and antibiotics.

The emergence of antibiotic-resistant bacteria (ARB) has necessitated the development of alternative therapies to deal with this global threat. Bacteriophages (viruses that target bacteria) that kill ARB are one such alternative. Although phages have been used clinically for decades with inconsistent results, a number of recent advances in phage selection, propagation, and purification have enabled a reevaluation of their utility in contemporary clinical medicine. In most phage therapy cases, phages are administered in combination with antibiotics to ensure that patients receive the standard-of-care treatment. Some phages may work cooperatively with antibiotics to eradicate ARB, as often determined using non-standardized broth assays. We sought to develop a solid media-based assay to assess cooperativity between antibiotics and phages to offer a standardized platform for such testing. We modeled the interactions that occur between antibiotics and phages on solid medium to measure additive, antagonistic, and synergistic interactions. We then tested the method using different bacterial isolates and identified a number of isolates where synergistic interactions were identified. These interactions were not dependent on the specific organism, phage family, or antibiotic used. A priori susceptibility to the antibiotic or the specific phage were not requirements to observe synergistic interactions. Our data also confirm the potential for the restoration of vancomycin to treat vancomycin-resistant Enterococcus (VRE) when used in combination with phages. Solid media assays for the detection of cooperative interactions between antibiotics and phages can be an accessible technique adopted by clinical laboratories to evaluate antibiotic and phage choices in phage therapy.IMPORTANCEBacteriophages have become an important alternative treatment for individuals with life-threatening antibiotic-resistant bacteria (ARB) infections. Because antibiotics represent the standard-of-care for treatment of ARB, antibiotics and phages often are delivered together without evidence that they work cooperatively. Testing for cooperativity can be difficult due to the equipment necessary and a lack of standardized means for performing the testing in liquid medium. We developed an assay using solid medium to identify interactions between antibiotics and phages for gram-positive and gram-negative bacteria. We modeled the interactions between antibiotics and phages on solid medium, and then tested multiple replicates of vancomycin-resistant Enterococcus (VRE) and Stenotrophomonas in the assay. For each organism, we identified synergy between different phage and antibiotic combinations. The development of this solid media assay for assessing synergy between phages and antibiotics will better inform the use of these combinations in the treatment of ARB infections.

Exploring the potential of bis(thiazol-5-yl)phenylmethane derivatives as novel candidates against genetically defined multidrug-resistant Staphylococcus aureus.

Antimicrobial resistance (AMR) represents an alarming global challenge to public health. Infections caused by multidrug-resistant Staphylococcus aureus (S. aureus) pose an emerging global threat. Therefore, it is crucial to develop novel compounds with promising antimicrobial activity against S. aureus especially those with challenging resistance mechanisms and biofilm formation. Series of bis(thiazol-5-yl)phenylmethane derivatives were evaluated against drug-resistant Gram-positive bacteria. The screening revealed an S. aureus-selective mechanism of bis(thiazol-5-yl)phenylmethane derivatives (MIC 2-64 μg/mL), while significantly lower activity was observed with vancomycin-resistant Enterococcus faecalis (MIC 64 μg/mL) (p<0.05). The most active phenylmethane-based (p-tolyl) derivative, 23a, containing nitro and dimethylamine substituents, and the naphthalene-based derivative, 28b, harboring fluorine and nitro substituents, exhibited strong, near MIC bactericidal activity against S. aureus with genetically defined resistance phenotypes such as MSSA, MRSA, and VRSA and their biofilms. The in silico modeling revealed that most promising compounds 23a and 28b were predicted to bind S. aureus MurC ligase. The 23a and 28b formed bonds with MurC residues at binding site, specifically Ser12 and Arg375, indicating consequential interactions essential for complex stability. The in vitro antimicrobial activity of compound 28b was not affected by the addition of 50% serum. Finally, all tested bis(thiazol-5-yl)phenylmethane derivatives showed favorable cytotoxicity profiles in A549 and THP-1-derived macrophage models. These results demonstrated that bis(thiazol-5-yl)phenylmethane derivatives 23a and 28b could be potentially explored as scaffolds for the development of novel candidates targeting drug-resistant S. aureus. Further studies are also warranted to understand in vivo safety, efficacy, and pharmacological bioavailability of bis(thiazol-5-yl)phenylmethane derivatives.

Genomic analysis of inter-hospital transmission of vancomycin-resistant Enterococcus faecium sequence type 80 isolated during an outbreak in Hiroshima, Japan.

Outbreaks caused by vancomycin-resistant enterococci that transcend jurisdictional boundaries are occurring worldwide. This study focused on a vancomycin-resistant enterococcus outbreak that occurred between 2018 and 2021 across two cities in Hiroshima, Japan. The study involved genetic and phylogenetic analyses using whole-genome sequencing of 103 isolates of vancomycin-resistant enterococci to identify the source and transmission routes of the outbreak. Phylogenetic analysis was performed using core genome multilocus sequence typing and core single-nucleotide polymorphisms; infection routes between hospitals were inferred using BadTrIP. The outbreak was caused by Enterococcus faecium sequence type (ST) 80 carrying the vanA plasmid, which was derived from strain A10290 isolated in India. Of the 103 isolates, 93 were E. faecium ST80 transmitted across hospitals. The circular vanA plasmid of the Hiroshima isolates was similar to the vanA plasmid of strain A10290 and transferred from E. faecium ST80 to other STs of E. faecium and other Enterococcus species by conjugation. The inferred transmission routes across hospitals suggest the existence of a central hospital serving as a hub, propagating vancomycin-resistant enterococci to multiple hospitals. Our study highlights the importance of early intervention at the key central hospital to prevent the spread of the infection to small medical facilities, such as nursing homes, with limited medical resources and a high number of vulnerable individuals.

The role of centre and country factors on process and outcome indicators in critically ill patients with hospital-acquired bloodstream infections.

The primary objective of this study was to evaluate the associations between centre/country-based factors and two important process and outcome indicators in patients with hospital-acquired bloodstream infections (HABSI). We used data on HABSI from the prospective EUROBACT-2 study to evaluate the associations between centre/country factors on a process or an outcome indicator: adequacy of antimicrobial therapy within the first 24h or 28-day mortality, respectively. Mixed logistical models with clustering by centre identified factors associated with both indicators. Two thousand two hundred nine patients from two hundred one intensive care units (ICUs) were included in forty-seven countries. Overall, 51% (n = 1128) of patients received an adequate antimicrobial therapy and the 28-day mortality was 38% (n = 839). The availability of therapeutic drug monitoring (TDM) for aminoglycosides everyday [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.03-2.14] or within a few hours (OR 1.79, 95% CI 1.34-2.38), surveillance cultures for multidrug-resistant organism carriage performed weekly (OR 1.45, 95% CI 1.09-1.93), and increasing Human Development Index (HDI) values were associated with adequate antimicrobial therapy. The presence of intermediate care beds (OR 0.63, 95% CI 0.47-0.84), TDM for aminoglycoside available everyday (OR 0.66, 95% CI 0.44-1.00) or within a few hours (OR 0.51, 95% CI 0.37-0.70), 24/7 consultation of clinical pharmacists (OR 0.67, 95% CI 0.47-0.95), percentage of vancomycin-resistant enterococci (VRE) between 10% and 25% in the ICU (OR 1.67, 95% CI 1.00-2.80), and decreasing HDI values were associated with 28-day mortality. Centre/country factors should be targeted for future interventions to improve management strategies and outcome of HABSI in ICU patients.

Private and well drinking water are reservoirs for antimicrobial resistant bacteria

Water quality testing does not recognise antimicrobial resistance (AMR) and is often limited to indicators of faecal contamination Escherichia coli and Enterococcus species. In Europe, data on AMR in drinking water is scarce. In Ireland, as in many countries, household drinking water is supplied via mains or via private wells or water schemes. Using citizen science, we identified Irish private drinking water supplies as reservoirs of antimicrobial resistant bacteria (ARB). Gram-negative (n = 464) and Gram-positive (n = 72) bacteria were isolated. We identified instances of potentially opportunistic ARB such as Enterobacter cloacae, Acinetobacter baumannii and Enterococcus species. We report reservoirs of multidrug resistance in Enterococcus casseliflavus, E. cloacae, E. coli, Stenotrophomonas maltophilia, and Serratia rubidaea. We also identified linezolid-resistant Enterococcus in Irish drinking water. Linezolid is a last-resort antibiotic used to treat vancomycin-resistant Enterococcus sp. Additionally, we identified mobile AMR in three water samples, two of which were carried on IncF group, one on IncQ and five on Col-like plasmids. Our work suggests that private drinking water is a potential sink and source of AMR pathogens. This highlights a value of drinking water surveillance in a One Health framework as the surveillance would provide information regarding the movement and persistence of ARB and ARGs that are able to survive in drinking water and subsequently have the opportunity to be mobilised through humans; linking the environment to the human and potentially threatening human health.

The impact of discontinuing single-room isolation of patients with vancomycin-resistant enterococci: a quasi-experimental single-centre study in South Korea

There is limited data on the effects of discontinuing single-room isolation while maintaining contact precautions, such as the use of gowns and gloves. In April 2021, our hospital ceased single-room isolation for patients with VRE because of single-room unavailability. This study assessed the impact of this policy by examining the incidence of hospital-acquired VRE bloodstream infections (HA-VRE BSI). This retrospective quasi-experimental study was conducted at a tertiary care hospital in Seoul, South Korea. Time-series analysis was used to evaluate HA-VRE BSI incidence at the hospital level and in the hematology unit before (phase 1) and after (phase 2) the policy change. At the hospital level, HA-VRE BSI incidence level (VRE BSI per 1000 patient-days per month) and trend did not change significantly between phase 1 and phase 2 (coefficient -0.015, 95% confidence interval [CI]: -0.053 - 0.023, P = 0.45 and 0.000, 95% CI: -0.002 - 0.002, P = 0.84, respectively). Similarly, HA-VRE BSI incidence level and trend in the hematology unit (-0.285, 95% CI: -0.618 - 0.048, P = 0.09 and -0.018, 95% CI: -0.036 - 0.000, P = 0.054, respectively) did not change significantly across the two phases. Discontinuing single-room isolation of VRE-colonized or infected patients was not associated with an increase in the incidence of VRE BSI at the hospital level or among high-risk patients in the hematology unit. Horizontal intervention for multidrug-resistant organisms, including measures like enhanced hand hygiene and environmental cleaning, may be more effective at preventing VRE transmission.

Spectrum and antibiotic resistance in community- and hospital-acquired urinary tract infections among adults: Experience from a large tertiary care center in a developing country.

It is important to note that the causative agents and patterns of antibiotic resistance vary between urinary tract infections (UTIs) acquired in the community and those acquired in a hospital setting. Therefore, the aim of this study was to compare the types of organisms and patterns of antibiotic resistance in adult patients with community-acquired urinary tract infections (CA-UTIs) and hospital-acquired urinary tract infections (HA-UTIs). Retrospectively, we collected urine samples from patients at An-Najah National University Hospital who experienced nonrecurring urinary tract infections (UTIs) between January 2019 and December 2020. The data were subsequently analyzed using IBM-SPSS® 21.0 software to determine the distribution of microorganisms and evaluate the rates of antibiotic resistance. A total of 798 nonrepetitive UTI patients were included in our study, in which more than half of the UTIs occurred in female patients (472; 59.1%), and most of the UTIs were of community origin (611; 76.6%). Both community-acquired urinary tract infections (CA-UTIs) and hospital-acquired urinary tract infections (HA-UTIs) were more common in female patients (45.6% and 13.5%, respectively). Escherichia coli was the most commonly isolated urinary pathogen in both the CA-UTIs and HA-UTIs. The five most common isolated urinary pathogens were E. coli, Klebsiella pneumoniae, Enterococcus faecalis, E. faecium, and Pseudomonas aeruginosa. Among the isolated bacteria, 28.2% were extended-spectrum beta-lactamase (ESBL)-producing bacteria, 4.1% were carbapenem-resistant Enterobacterales (CRE), and 6.5% were vancomycin-resistant Enterococci. The most commonly isolated urinary pathogens from HA-UTIs showed higher resistance rates against all the tested antibiotics except for E. faecium, which showed greater resistance to tetracycline (42.5%) and quinupristin/dalfopristin (17.5%) in CA-UTIs. There are similarities in the etiological profiles of CA-UTI and HA-UTI, but the resistance rates are high, and urine culture is essential for the correct treatment of individual cases, even in primary care.

Analysis of the Frequency, Antibiotic Susceptibility, and Related Genes among Foodborne Pathogenic Bacteria Isolated from Hospital Refrigerators in Tehran, Iran

Background: Hospital refrigerators as essential food storage can be important source of food contamination. We aimed to investigate the frequency and antibiotic susceptibility of the pathogenic bacteria in three hospital refrigerators in Tehran.&#x0D; Methods: This study was performed on 254 samples, collected from 60 refrigerators of the various wards of three hospitals, A, B, and C, in Tehran, Iran from 2020 to 2021. Following isolation and identification of isolates, the antibiotic susceptibility pattern was determined. PCR-based assays were used to screen the presence of antibiotic resistance genes of resistant isolates.&#x0D; Results: From 254 collected samples, 236 samples (92.9%) were contaminated. Most strains were isolated from refrigerators with poorly cleaned, temperatures above 8 °C in non-critical wards. Most bacteria belonging to Enterobacteriaceae (68.8%), followed by Staphylococcus (11.9%), and Enterococcus (10.6%), while the frequency of non-Enterobacteriaceae isolates was 8.9%. The highest antibiotic resistant bacteria were in extended spectrum beta-lactamase (ESBL) 9.7%, vancomycin-resistant enterococci (VRE) 5.3%, methicillin-resistant S. epidermidis (MRSE) 0.4%, and methicillin-resistant S. aureus (MRSA) 0.4%, respectively. The blaOXA-48, blaCTX, and bclaTEM genes were found only in 10% of Enterobacteriaceae isolates. The blaOXA-51 gene was found in all non-Enterobacteriaceae isolates. The vanA and mecA genes were detected in antibiotic-resistant Enterococcus and Staphylococcus.&#x0D; Conclusion: Our findings suggests major concern about cross-contamination and the emergence of antibiotic-resistant isolates as a potential health threat with hospital refrigerators origin. More attention to hospital refrigerators cleaning is necessary to prevent foodborne diseases and nosocomial infections.

Antibacterial, antibiofilm, and antioxidant impacts of usnic acid against vancomycin-resistant enterococcus

Antibacterial, antibiofilm, and antioxidant impacts of usnic acid against vancomycin-resistant enterococcus

LiaX is a surrogate marker for cell envelope stress and daptomycin non-susceptibility in Enterococcus faecium.

Daptomycin (DAP) is often used as a first-line therapy to treat vancomycin-resistant Enterococcus faecium infections, but emergence of DAP non-susceptibility threatens the effectiveness of this antibiotic. Moreover, current methods to determine DAP minimum inhibitory concentrations (MICs) have poor reproducibility and accuracy. In enterococci, DAP resistance is mediated by the LiaFSR cell membrane stress response system, and deletion of liaR encoding the response regulator results in hypersusceptibility to DAP and antimicrobial peptides. The main genes regulated by LiaR are a cluster of three genes, designated liaXYZ. In Enterococcus faecalis, LiaX is surface-exposed with a C-terminus that functions as a negative regulator of cell membrane remodeling and an N-terminal domain that is released to the extracellular medium where it binds DAP. Thus, in E. faecalis, LiaX functions as a sentinel molecule recognizing DAP and controlling the cell membrane response, but less is known about LiaX in E. faecium. Here, we found that liaX is essential in E. faecium with an activated LiaFSR system. Unlike E. faecalis, E. faecium LiaX is not detected in the extracellular milieu and does not appear to alter phospholipid architecture. We further postulated that LiaX could be used as a surrogate marker for cell envelope activation and non-susceptibility to DAP. For this purpose, we developed and optimized a LiaX enzyme-linked immunosorbent assay (ELISA). We then assessed 86 clinical E. faecium bloodstream isolates for DAP MICs and used whole genome sequencing to assess for substitutions in LiaX. All DAP-resistant clinical strains of E. faecium exhibited elevated LiaX levels. Strikingly, 73% of DAP-susceptible isolates by standard MIC determination also had elevated LiaX ELISAs compared to a well-characterized DAP-susceptible strain. Phylogenetic analyses of predicted amino acid substitutions showed 12 different variants of LiaX without a specific association with DAP MIC or LiaX ELISA values. Our findings also suggest that many E. faecium isolates that test DAP susceptible by standard MIC determination are likely to have an activated cell stress response that may predispose to DAP failure. As LiaX appears to be essential for the cell envelope response to DAP, its detection could prove useful to improve the accuracy of susceptibility testing by anticipating therapeutic failure.

Impact of Genital Infections and Antibiotic Use on Incidence of Preterm Birth: A Retrospective Observational Study.

This study investigates the complex interplay among genital infections, antibiotic usage, and preterm birth. This study aims to identify common genital pathogens associated with preterm births, assess the impact of various antibiotic treatments on pregnancy outcomes, and understand antibiotic resistance patterns among these pathogens. This study included 71 pregnant women who experienced preterm birth and 94 women with genital infections who delivered at term. Various maternal characteristics, medical history, signs and symptoms, gestational weight, gestational age, type of birth, vaginal pH, Nugent scores, and vaginal flora were analyzed. Antibiotic resistance patterns of isolated microorganisms were also examined. The prevalence of sexually transmitted diseases (STDs) and genital herpes was significantly higher in the preterm group. Preterm births were associated with fever, pelvic pain, vaginal spotting, and fatigue. Vaginal pH levels and Nugent scores were significantly higher in the preterm group, indicating disturbed vaginal flora. The presence of Extended-Spectrum Beta-Lactamases (ESBLs) was a particularly strong risk factor, increasing by more than four times the odds of preterm birth (OR = 4.45, p = 0.001). Vancomycin-Resistant Enterococci (VRE) presence was another critical factor, with a four-fold increase in the odds of preterm birth (OR = 4.01, p = 0.034). The overall presence of Multidrug-Resistant (MDR) organisms significantly increased the odds of preterm birth (OR = 3.73, p = 0.001). Specific pathogens like Chlamydia trachomatis (OR = 3.12, p = 0.020) and Mycoplasma hominis (OR = 3.64, p = 0.006) were also identified as significant risk factors. Ureaplasma urealyticum also showed a significantly higher risk of preterm birth (OR = 2.76, p = 0.009). This study highlights the importance of screening for and treating genital infections during pregnancy, especially STDs and genital herpes, as they can significantly increase the risk of preterm birth. Additionally, the presence of specific microorganisms and antibiotic resistance patterns plays an essential role in preterm birth risk. Early detection and targeted antibiotic treatment may help mitigate this risk and improve pregnancy outcomes.

Antimicrobial resistance of clinical bacterial isolates in China: current status and trends.

Antimicrobial resistance surveillance systems have been established in China. Two representative national surveillance networks are the China Antimicrobial Surveillance Network (CHINET) and China Antimicrobial Resistance Surveillance System (CARSS), both of which were established in 2005. For all clinical isolates collected in both of these surveillance networks, the ratio of Gram-negative bacilli to Gram-positive cocci was approximately 7:3 during the past 18 years. Generally, Gram-negative bacilli have a higher antimicrobial resistance profile in China. The prevalence of ESBLs in Escherichia coli is as high as approximately 50%. Acinetobacter baumannii-calcoaceticus complex (ABC) has a high antimicrobial resistance profile, with a carbapenem resistance rate of approximately 66%. However, the prevalence of carbapenem-resistant ABC has also shown a decreasing trend from 2018 to 2022. The prevalence of vancomycin-resistant Enterococcus was low, and the prevalence of MRSA and carbapenem-resistant Pseudomonas aeruginosa showed decreasing trends from 2005 to 2022. CHINET surveillance data demonstrated that the prevalence of carbapenem-resistant Klebsiella pneumoniae showed a remarkable increasing trend from 2.9% (imipenem resistance) in 2005 to 25.0% in 2018, and then slightly decreased to 22.6% in 2022. The decreasing trends may reflect the antimicrobial stewardship efforts in China: a professional consensus on the rational clinical use of carbapenems was issued by the National Health Commission of China and was well implemented nationally; after that, the clinical use of carbapenems decreased slightly in China.