Linezolid-resistant Enterococcus Research Articles

Complete genome sequence of the linezolid-resistant clinical Enterococcus faecalis N23-3408 linked to a livestock lineage in Switzerland.

Here, we report the complete genome of human clinical linezolid-resistant Enterococcus faecalis N23-3408. N23-3408 harbored a 59.5 kb plasmid with antimicrobial resistance genes cat, erm(B), fexA, optrA, tet(L), and tet(M). Closely related E. faecalis harboring this plasmid was previously obtained from livestock animals and pet food in Switzerland.

Linezolid-resistant Enterococcus isolates in Menoufia University Hospitals and community-acquired infections: Genetic determinants and risk factors

Linezolid-resistant Enterococcus isolates in Menoufia University Hospitals and community-acquired infections: Genetic determinants and risk factors

Genomic epidemiology reveals multiple mechanisms of linezolid resistance in clinical enterococci in China

BackgroundInfections caused by linezolid-resistant enterococci (LRE) are clinically difficult to treat and threaten patient health. However, there is a lack of studies on long time-span LRE strains in China. For this reason, our study comprehensively revealed the resistance mechanisms of LRE strains collected in a Chinese tertiary care hospital from 2011 to 2022.MethodsEnterococcal strains were screened and verified after retrospective analysis of microbial data. Subsequently, 65 LRE strains (61 Enterococcus faecalis and 4 Enterococcus faecium, MIC ≥ 8 µg/ml), 1 linezolid-intermediate Enterococcus faecium (MIC = 4 µg/ml) and 1 linezolid-susceptible Enterococcus faecium (MIC = 1.5 µg/ml) were submitted for whole-genome sequencing (WGS) analysis and bioinformatics analysis.ResultsThe optrA gene was found to be the most common linezolid resistance mechanism in our study. We identified the wild-type OptrA and various OptrA variants in 98.5% of LRE strains (61 Enterococcus faecalis and 3 Enterococcus faecium). We also found one linezolid-resistant Enterococcus faecium strain carried both optrA and cfr(D) gene, while one linezolid-resistant Enterococcus faecium only harbored the poxtA gene. Most optrA genes (55/64) were located on plasmids, with impB-fexA-optrA, impB-fexA-optrA-erm(A), fexA-optrA-erm(A), and fexA-optrA segments. A minority of optrA genes (9/64) were found on chromosomes with the Tn6674-like platform. Besides, other possible linezolid resistance-associated mechanisms (mutations in the rplC and rplD genes) were also found in 26 enterococcal strains.ConclusionsOur study suggested that multiple mechanisms of linezolid resistance exist among clinical LRE strains in China.

Identification of an Enterococcus faecium strain isolated from raw bovine milk co-harbouring the oxazolidinone resistance genes optrA and poxtA in China

Oxazolidinones are potent antimicrobial agents used to treat human infections caused by multidrug-resistant Gram-positive bacteria. The growing resistance to oxazolidinones poses a significant threat to public health. In August 2021, a linezolid-resistant Enterococcus faecium BN83 was isolated from a raw milk sample of cow in Inner Mongolia, China. This isolate exhibited a multidrug resistance phenotype and was resistant to most of drugs tested including linezolid and tedizolid. PCR detection showed that two mobile oxazolidinones resistance genes, optrA and poxtA, were present in this isolate. Whole genome sequencing analysis revealed that the genes optrA and poxtA were located on two different plasmids, designated as pBN83–1 and pBN83–2, belonging to RepA_N and Inc18 families respectively. Genetic context analysis suggested that optrA gene on plasmid pBN83–1 was located in transposon Tn6261 initially found in E. faecalis. Comprehensive analysis revealed that Tn6261 act as an important horizontal transmission vector for the spread of optrA in E. faecium. Additionally, poxtA-bearing pBN83–2 displayed high similarity to numerous plasmids from Enterococcus of different origin and pBN83–2-like plasmid represented a key mobile genetic element involved in movement of poxtA in enterococcal species. The presence of optrA- and poxtA-carrying E. faecium in raw bovine milk represents a public health concern and active surveillance is urgently warranted to investigate the prevalence of oxazolidinone resistance genes in animal-derived food products.

Epidemiology and genetic diversity of linezolid-resistant Enterococcus clinical isolates in Belgium from 2013 to 2021

ObjectivesLinezolid-resistant opportunistic human pathogens Enterococcus faecalis and Enterococcus faecium are emerging health threats as limited therapeutic options remain. The aim of this study was to investigate the epidemiology, resistance mechanisms, and genetic diversity of linezolid-resistant enterococci (LRE) isolated between 2013 and 2021 and received at the Belgian National Reference Centre (NRC) for Enterococci. MethodsLinezolid susceptibility testing was performed upon request on 2458 submitted enterococci strains. Whole-genome sequencing was performed on all LRE strains. ResultsSeventy-eight LRE human isolates, of which 63 (81%) E. faecalis and 15 (19%) E. faecium strains, were submitted to the Belgian NRC for Enterococci. Of the linezolid-resistant E. faecalis strains, 97% harboured the optrA gene (56% wild-type pE349) and 3% the poxtA gene. Of the linezolid-resistant E. faecium strains, 54% harboured the G2576T point mutation in the V domain of the 23S rRNA genes, 23% the poxtA, and 23% the optrA gene. Furthermore, two E. faecium strains were identified with a combination of two resistance mechanisms ([i] optrA and poxtA, and [ii] cfr(B) and G2576T point mutation, respectively). Vancomycin resistance was observed in 15% (n = 12) of the LRE. ST480 (n = 42/63 typed strains, 67%) was the most frequently detected sequence type (ST) in linezolid-resistant E. faecalis strains, while ST203 (n = 5/15 typed strains, 33%) was the most frequently detected ST in linezolid-resistant E. faecium strains. ConclusionsE. faecalis isolates harbouring optrA were the predominant LRE in Belgium, with ST480 as the most prominent multilocus sequence typing. Linezolid resistance in E. faecium could be attributed to either chromosomal mutations or transferable resistance determinants.

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.

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.

Risk factors and outcome associated with the acquisition of MDR linezolid-resistant Enterococcus faecium: a report from tertiary care centre.

The aim of the study was to determine the resistance profile of linezolid-resistant Enterococcus faecium (LREfm) and to investigate risk factors and outcomes associated with LREfm infections. A prospective case-control study was undertaken (2019 to 2022) and included 202 patients with LREfm infections (cases) and 200 controls with LSEfm infections. Clinical data was prospectively collected and analysed for risk factors and outcomes. Antimicrobial susceptibility was performed, and resistance profile was studied using WHOnet. Risk factors associated with LREfm infection were site of infection UTI (OR 5.87, 95% CI 2.59-13.29, p ≤ 0.001), prior use of carbapenem (OR 2.85 95% CI 1.62-5.02, p ≤ 0.001) and linezolid (OR 10.13, 95% CI 4.13-24.82, p ≤ 0.001), use of central line (OR 5.54, 95% CI 2.35-13.09, p ≤ 0.001), urinary catheter (OR 0.29, 95% CI 0.12-0.70, p ≤ 0.001) and ventilation (OR 14.87, 95% CI 7.86-28.11, p ≤ 0.007). The hospital stay 8-14 days (< 0.001) prior to infection and the mortality rate (p = 0.003) were also significantly high among patients with LREfm infections. Linezolid and vancomycin resistance coexisted; further, MDR, XDR and PDR phenotypes were significantly higher among LREfm. This study provided insight into epidemiology of MDR LREfm in a setting where linezolid use is high. The main drivers of infections with LREfm are multiple, including use of carbapenems and linezolid. Invasive procedures and increased hospital stay facilitate spread through breach in infection control practises. As therapeutic options are limited, ongoing surveillance of LREfm and VRE is critical to guide appropriate use of linezolid and infection control policies.

Global spread of the linezolid-resistant Enterococcus faecalis ST476 clonal lineage carrying optrA.

To investigate the global distribution of an optrA-harbouring linezolid-resistant Enterococcus faecalis ST476 clonal lineage. Comprehensive searches of the NCBI database were performed to identify published peer-reviewed articles and genomes of E. faecalis ST476. Each genome was analysed for resistome, virulome, OptrA variant and optrA genetic contexts. A phylogenetic comparison of ST476 genomes with publicly available genomes of other STs was also performed. Sixty-six E. faecalis ST476 isolates from 15 countries (China, Japan, South Korea, Austria, Denmark, Spain, Czech Republic, Colombia, Tunisia, Italy, Malaysia, Belgium, Germany, United Arab Emirates and Switzerland) mainly of human and animal origin were identified. Thirty available ST476 genomes compared with genomes of 591 STs indicated a progressive radiation of E. faecalis STs starting from ST21. The closest ancestral node for ST476 was ST1238. Thirty E. faecalis ST476 genomes exhibited 3-916 SNP differences. Several antimicrobial resistance and virulence genes were conserved among the ST476 genomes. The optrA genetic context exhibited a high degree of or complete identity to the chromosomal transposon Tn6674. Only three isolates displayed an optrA-carrying plasmid with complete or partial Tn6674. The WT OptrA protein was most widespread in the ST476 lineage. Linezolid-resistant optrA-carrying E. faecalis of the clonal lineage ST476 is globally distributed in human, animal and environmental settings. The presence of such an emerging clone can be of great concern for public health. Thus, a One Health approach is needed to counteract the spread and the evolution of this enterococcal clonal lineage.

Detection of linezolid and vancomycin resistant Enterococcus isolates collected from healthy chicken caecum.

The poultry industry represents an important economic sector in Tunisia. This study aims to determine the antimicrobial resistance phenotypes and genotypes and virulence factors of enterococci collected from chicken caecum in Tunisia. Forty-nine composite chicken caecum samples were recovered in 49 different Tunisian farms (December 2019-March 2020). Each composite sample corresponds to six individual caecum from each farm. Composite samples were plated on Slanetz-Bartley agar both supplemented (SB-Van) and not supplemented (SB) with vancomycin and isolates were identified by matrix-assisted laser desorption/ionization time-of-flight. Antibiotic resistance and virulence genes were tested by Polymerase Chain Reaction (PCR) and sequencing and multilocus-sequence-typing of selected enterococci was performed. One hundred sixty seven enterococci of six different species were recovered. Acquired linezolid resistance was detected in 6 enterococci of 4/49 samples (8.1%): (A) four optrA-carrying Enterococcus faecalis isolates assigned to ST792, ST478, and ST968 lineages; (B) two poxtA-carrying Enterococcus faecium assigned to ST2315 and new ST2330. Plasmid typing highlighted the presence of the rep10, rep14, rep7, rep8, and pLG1 in these strains. One vancomycin-resistant E. faecium isolate (typed as ST1091) with vanA gene (included in Tn1546) was detected in SB-Van plates. The gelE, agg, esp, and hyl virulence genes were found in linezolid- and vancomycin-resistant enterococci. High resistance rates were identified in the enterococci recovered in SB plates: tetracycline [74.8%, tet(M) and tet(L) genes], erythromycin [65.9%, erm(B)], and gentamicin [37.1%, aac(6')-Ie-aph(2″)-Ia]. The detection of emerging mechanisms of resistance related to linezolid and vancomycin in the fecal enterococci of poultry farms has public health implications, and further surveillance should be carried out to control their dissemination by the food chain.

Linezolid Resistance Genes and Mutations among Linezolid-Susceptible Enterococcus spp.-A Loose Cannon?

The National Reference Centre for Enterococci receives an increasing number of linezolid-resistant Enterococcus isolates. Linezolid (LIN) resistance is mediated by G2576T 23S rDNA gene mutations and/or acquisition of resistance genes (cfr, optrA, poxtA). There are anecdotal reports that those resistance traits may be present in phenotypically linezolid-susceptible isolates. We aimed to determine the prevalence of LIN resistance genes and mutations in enterococci with a LIN MIC of 4 mg/L in broth microdilution (EUCAST = susceptible) isolated from German hospital patients 2019-2021. LIN MICs were additionally determined by ETEST® and VITEK2. Selected strains were subjected to LIN selective pressure and growth was monitored with increasing antibiotic concentrations. We received 195 isolates (LIN MIC = 4 mg/L). In total, 78/195 (40%) isolates contained either a putative resistance gene, the G2576T mutation, or a combination thereof. Very major error was high for broth microdilution. The ability to predict phenotypic resistance from genotypic profile was highest for G2576T-mediated resistance. Selection experiments revealed that, in particular, E. faecium isolates with resistance gene mutations or poxtA rapidly adapt to MICs above the clinical breakpoint. In conclusion, LIN resistance genes and mutations can be observed in phenotypically linezolid-susceptible enterococci. Those isolates may rapidly develop resistance under LIN selective pressure potentially leading to treatment failure.

Off-label oritavancin treatment outcome and molecular characterization of a vancomycin- and linezolid-resistant Enterococcus faecium causing liver abscesses.

Off-label oritavancin treatment outcome and molecular characterization of a vancomycin- and linezolid-resistant Enterococcus faecium causing liver abscesses.

Membrane vesicles derived from Enterococcus faecalis promote the co-transfer of important antibiotic resistance genes located on both plasmids and chromosomes.

Bacterial membrane vesicles (BMVs) are novel vehicles of antibiotic resistance gene (ARG) transfer in Gram-negative bacteria, but their role in the spread of ARGs in Gram-positive bacteria has not been defined. The purpose of this study was to evaluate the role of MVs in the transmission of antimicrobial resistance in Gram-positive bacteria. A linezolid-resistant Enterococcus faecalis CQ20 of swine origin was selected as the donor strain. Linezolid-susceptible E. faecalis SC032 of human origin, Enterococcus faecium BM4105 and Escherichia coli were selected as recipient strains. The presence of plasmids (pCQ20-1 and pCQ20-2) and an optrA-carrying transposon Tn6674 in CQ20, MVs and vesiculants was verified by WGS or PCR. MVs were isolated with density gradient centrifugation, and MV-mediated transformation was performed to assess the horizontal transferability of MVs. The MICs for CQ20 and its vesiculants were determined by the broth microdilution method. CQ20-derived MVs (CQ20-MV) were isolated, and PCR identified the presence of two plasmids and the optrA gene in the CQ20-MVs. MV-mediated transformation to E. faecalis SC032 and E. faecium BM4105 was successfully performed, and the WGS data also showed that both plasmids pCQ20-1 and pCQ20-2 and optrA-carrying transposon Tn6674 were transferred to E. faecalis SC032 and E. faecium BM4105, but failed for E. coli. Additionally, vesiculants that had acquired ARGs still had the ability to spread these genes via MVs. To our knowledge, this is the first report of MV-mediated co-transfer of ARG-carrying plasmids and transposons in the Gram-positive bacterium E. faecium.

Risk exploration and prediction model construction for linezolid-resistant Enterococcus faecalis based on big data in a province in southern China

BackgroundEnterococcus faecalis is a common cause of healthcare-associated infections. Its resistance to linezolid, the antibiotic of last resort for vancomycin-resistant enterococci, has become a growing threat in healthcare settings.MethodsWe analyzed the data of E. faecalis isolates from 26 medical institutions between 2018 and 2020 and performed univariate and multivariate logistic regression analyses to determine the independent predictors for linezolid-resistant E. faecalis (LREFs). Then, we used the artificial neural network (ANN) and logistic regression (LR) to build a prediction model for linezolid resistance and performed a performance evaluation and comparison.ResultsOf 12,089 E. faecalis strains, 755 (6.25%) were resistant to linezolid. Among vancomycin-resistant E. faecalis, the linezolid-resistant rate was 24.44%, higher than that of vancomycin-susceptible E. faecalis (p < 0.0001). Univariate and multivariate regression analyses showed that gender, age, specimen type, length of stay before culture, season, region, GDP (gross domestic product), number of beds, and hospital level were predictors of linezolid resistance. Both the ANN and LR models constructed in the study performed well in predicting linezolid resistance in E. faecalis, with AUCs of 0.754 and 0.741 in the validation set, respectively. However, synthetic minority oversampling technique (SMOTE) did not improve the prediction ability of the models.ConclusionE. faecalis linezolid-resistant rates varied by specimen site, geographic region, GDP level, facility level, and the number of beds. At the same time, community-acquired E. faecalis with linezolid resistance should be monitored closely. We can use the prediction model to guide clinical medication and take timely prevention and control measures.

Thiazolopyrimidinone Derivative H5-23 Enhances Daptomycin Activity against Linezolid-Resistant Enterococcus faecalis by Disrupting the Cell Membrane.

The increasing emergence and dissemination of multidrug-resistant (MDR) Gram-positive pathogens pose a serious threat to global public health. Previous reports have demonstrated that the compound H5-23, which has a thiazolopyrimidinone core structure, exhibited antibacterial activity against Staphylococcus epidermidis in vitro. However, the antibacterial activity in vivo and mechanism of action of H5-23 against MDR bacteria have not been fully studied. In this study, we report that H5-23 has wide-spectrum antibacterial activity against Gram-positive bacteria. When combined with daptomycin (DAP), H5-23 demonstrates enhanced antimicrobial activity, effectively killing both planktonic and persister cells, as well as eradicating biofilm formation by linezolid-resistant Enterococcus faecalis. The development of resistance shows that H5-23 has a low propensity to induce antibiotic resistance compared to that of linezolid in vitro. Mechanistic studies reveal that H5-23 increases membrane permeability and disrupts membrane integrity, resulting in increased production of reactive oxygen species (ROS), metabolic perturbations, and ultimately cell death. Additionally, we demonstrate the synergistic antibacterial effect of H5-23 combined with DAP in a murine model. These findings suggest that H5-23 is a promising antimicrobial agent and provides a potential strategy for enhancing the efficacy of DAP in combating multidrug-resistant E. faecalis.

Molecular epidemiology, phenotypic and genomic characterization of antibiotic-resistant enterococcal isolates from diverse farm animals in Xinjiang, China

Multidrug-resistant (MDR) bacteria in farm environments can be transferred to humans through the food chain and occupational exposure. Enterococcus infections caused by linezolid resistant enterococci (LRE) are becoming more challenging to treat as their resistance to antibiotics intensifies. Therefore, this study investigated the molecular epidemiology, phenotypic and genomic characterization of enterococci in seven species of farm animals (sheep, chicken, swine, camel, cattle, equine, pigeon) anal swab from Xinjiang, China by agar dilution method, polymerase chain reaction (PCR), whole-genome sequencing (WGS) and bioinformatics analysis. A total of 771 samples were collected, 599 (78 %) were contaminated with Enterococcus spp., among which Enterococcus faecalis (350/599) was dominant. Antimicrobial susceptibility testing showed that high resistance was observed in rifampicin (80 %), tetracycline (71 %), doxycycline (71 %), and erythromycin (69 %). The results of PCR showed the highest prevalent antibiotic resistance genes (ARGs) were aac(6′)-aph(2″) (85 %), followed by tet(M) (73 %), erm(B) (62 %), and aph(3′)-IIIa (61 %). Besides, 29 optrA-carrying E. faecalis isolates belonging to 13 STs (including 3 new alleles) were detected, with ST714 (31 %, 9/29) being the dominant ST type. The phylogenetic tree showed that optrA-carrying E. faecalis prevalent in the intensive swine farm is mainly caused by clonal transmission. Notably, optrA gene in Enterococcus spp. isolate from camel was first characterized here. WGS of E. faecalis F109 isolate from camel confirmed the colocalization of optrA with other five ARGs in the same plasmid (pAFL-109F). The optrA-harboring genetic context is IS1216E-fexA-optrA-erm(A)-IS1216E. This study highlights the prevalence of MDR Enterococcus (≥88 %) and four ARGs (≥75 %) in swine (intensive farming), cattle (commercial farming), and chickens (backyard farming) are high and also highlights that optrA-carrying E. faecalis of farm animals incur a transmission risk to humans through environment, food consumption and others. Therefore, antibiotic-resistant bacteria (ARB) monitoring and effective control measures should be strengthened and implemented in diverse animals.

The epidemiology of multidrug-resistant organisms in persons diagnosed with cancer in Norway, 2008–2018: expanding surveillance using existing laboratory and register data

Surveillance has revealed an increase of multidrug-resistant organisms (MDROs), even in low-prevalent settings such as Norway. MDROs pose a particular threat to at-risk populations, including persons with cancer. It is necessary to include such populations in future infection surveillance. By combining existing data sources, we aimed to describe the epidemiology of MDROs in persons diagnosed with cancer in Norway from 2008 to 2018. A cohort was established using data from the Cancer Registry of Norway, which was then linked to notifications of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin- and/or linezolid-resistant enterococci (V/LRE), and carbapenemase-producing Gram-negative bacilli (CP-GNB) from the Norwegian Surveillance System for Communicable Diseases, and laboratory data on third-generation cephalosporin-resistant Enterobacterales (3GCR-E) from Oslo University Hospital (OUH). We described the incidence of MDROs and resistance proportion in Enterobacterales from 6 months prior to the person’s first cancer diagnosis and up to 3 years after. The cohort included 322,005 persons, of which 0.3% (878) were diagnosed with notifiable MDROs. Peak incidence rates per 100,000 person-years were 60.9 for MRSA, 97.2 for V/LRE, and 6.8 for CP-GNB. The proportion of 3GCR-E in Enterobacterales in blood or urine cultures at OUH was 6% (746/12,534). Despite overall low MDRO incidence, there was an unfavourable trend in the incidence and resistance proportion of Gram-negative bacteria. To address this, there is a need for effective infection control and surveillance. Our study demonstrated the feasibility of expanding the surveillance of MDROs and at-risk populations through the linkage of existing laboratory and register data.

The Synergistic Activity of Rhamnolipid Combined with Linezolid against Linezolid-Resistant Enterococcus faecium.

Enterococci resistance is increasing sharply, which poses a serious threat to public health. Rhamnolipids are a kind of amphiphilic compound used for its bioactivities, while the combination of nontraditional drugs to restore linezolid activity is an attractive strategy to treat infections caused by these pathogens. This study aimed to investigate the activity of linezolid in combination with the rhamnolipids against Enterococcus faecium. Here, we determined that the rhamnolipids could enhance the efficacy of linezolid against enterococci infections by a checkerboard MIC assay, a time-kill assay, a combined disk test, an anti-biofilm assay, molecular simulation dynamics, and mouse infection models. We identified that the combination of rhamnolipids and linezolid restored the linezolid sensitivity. Anti-biofilm experiments show that our new scheme can effectively inhibit biofilm generation. The mouse infection model demonstrated that the combination therapy significantly reduced the bacterial load in the feces, colons, and kidneys following subcutaneous administration. This study showed that rhamnolipids could play a synergistic role with linezolid against Enterococcus. Our combined agents could be appealing candidates for developing new combinatorial agents to restore antibiotic efficacy in the treatment of linezolid-resistant Enterococcus infections.

Are enterococcal bloodstream infections an independent risk factor for a poorer 5-year survival or just a marker for severity of illness?-The Munich multicentric enterococci cohort.

The present study provides a substantial contribution to literature, showing that patients with enterococcal bloodstream infections (BSI) have a lower survival rate than those with Escherichia coli (E. coli) bloodstream infections after adjusting for 17 limiting prognostic factors and excluding patients with a limited life expectancy [metastatic tumor disease, Charlson Comorbidity Index (CCI) (greater than or equal to) 5]. This difference in the 5-year long-term survival was mainly driven by Enterococcus faecium (ECFM) bloodstream infections, with vancomycin resistance not being a significant contributing factor. Our findings imply that E. faecium bloodstream infections seem to be an independent risk factor for poor long-term outcomes. As such, future research should confirm this relationship and prioritize investigating its causality through prospective studies.

The emergence of multidrug-resistant Gram-positive bloodstream infections in India - a single center prospective cohort study.

Gram-positive bloodstream infections (BSIs) are an emerging health concern, especially in resource-limited settings. There is a paucity of data regarding the antimicrobial resistance (AMR) pattern of Gram-positive BSIs. The rise in multidrug-resistant infections further convoluted antibiotic selection. We aimed to assess the incidence, clinical and microbiological profile, antimicrobial resistance (AMR) and outcome in Gram-positive BSIs. This was a single-center prospective study conducted at a tertiary care hospital in Western India. All patients (age ≥18 years) with culture-proven Gram-positive BSIs were included. Data were collected on all patients' demography, risk factors, AMR and clinical outcome. A total of 210 clinically significant isolates were grown from July 2020 to December 2021. The incidence of Gram-positive BSIs was 29% (n=61); 55.9% of cases were healthcare-associated, while 44.1% were community-acquired. Coagulase-negative staphylococci (CoNS) were the major isolates (36.1%), followed by Enterococcus spp. (27.9%), methicillin-susceptible Staphylococcus aureus (MSSA) (18%) and methicillin-resistant Staphylococcus aureus (MRSA) (14.7%). The proportion of vancomycin and teicoplanin-resistant CoNS isolates was 13.6% and 19%. Among Enterococcus isolates, the proportion of vancomycin-resistant enterococci (VRE) and linezolid-resistant enterococci (LRE) were 11.8% and 5.9%. The overall mortality in Gram-positive BSIs was 42.6%. Older age, MRSA infection, septic shock, and high NLR were significantly associated with mortality. On the Cox regression model, age ≥65 years (HR: 2.5; 95%CI: 1.1-5.8; p=0.024) and MRSA infection (HR: 3.6; 95%CI: 1.5-8.5; p=0.021) were found as independent predictors of 30-day mortality. This study found substantial mortality with Gram-positive BSIs, especially MRSA infections. Moreover, the emergence of VRE and LRE is also alarming. Active surveillance of AMR and evaluation of mortality predictors may help overcome the therapeutic challenges in managing BSIs.