Enterococcal Infections Research Articles

Conjugation of Polycationic Peptides Extends the Efficacy Spectrum of β-Lactam Antibiotics.

Antibiotic-resistant enterococci represent a significant global health challenge. Unfortunately, most β-lactam antibiotics are not applicable for enterococcal infections due to intrinsic resistance. To extend their antimicrobial spectrum, polycationic peptides are conjugated to examples from each of the four classes of β-lactam antibiotics. Remarkably, the β-lactam-peptide conjugates gained an up to 1000-fold increase in antimicrobial activity against vancomycin-susceptible and vancomycin-resistant enterococci. Even against β-lactam-resistant Gram-negative strains, the conjugates are found to be effective despite their size exceeding the exclusion volume of porins. The extraordinary gain of activity can be explained by an altered mode of killing. Of note, the conjugates showed a concentration-dependent activity in contrast to the parent β-lactam antibiotics that exhibited a time-dependent mode of action. In comparison to the parent β-lactams, the conjugates showed altered affinities to the penicillin-binding proteins. Furthermore, it is found that peptide conjugation also resulted in a different elimination route of the compounds when administered to rodents. In mice systemically infected with vancomycin-resistant enterococci, treatment with a β-lactam-peptide conjugate reduced bacterial burden in the liver compared to its originator. Therefore, peptide modification of β-lactam antibiotics represents a promising platform strategy to broaden their efficacy spectrum, particularly against enterococci.

Molecular Characterization of Enterococcus faecium Clinical Isolates Harbouring erm (T) from an Italian Hospital.

The presence of erm(T) gene conferring resistance to macrolides, lincosamides and streptogramin B (MLSB), was screened in 296 enterococci collected from clinical samples in a central Italy hospital and seven Enterococcus faecium isolates resulted positive to erm(T) by PCR. All isolates were resistant to erythromycin, tetracycline, ciprofloxacin and ampicillin but susceptible to vancomycin and chloramphenicol. Whole Genome Sequencing analysis revealed that in five E. faecium isolates, all belonging to the sequence type ST80 included in the clonal complex CC17 responsible of nosocomial infections, erm (T) gene was chromosome-located, in different genetic contexts. In E. faecium 735,236, erm (T) was on a 4,159-bp region flanked by two IS1216 and inserted at the 3' end of the mp gene. In E. faecium 711,448 and 739,437, erm (T) was found in a 4,463-bp region identical to that detected in E. faecium 735,236 except for 319bp. In E. faecium 713,729 and 757,415, erm (T) was on a 7,038-bp region flanked by IS1251 and ISEfm2 transposases and encompassed between the genes encoding a recombinase and three hypothetical proteins. erm(T)-carrying minicircles were detected in all isolates by inverse PCR assays demonstrating that erm(T) was included in mobile elements. However, in conjugation assays by filter mating, the erm(T) transferability was unsuccessful. Although macrolides are not used to treat enterococcal infections, the resistance is nonetheless widespread. These antibiotics are critically important in human medicine, but only few studies focused on erm (T)-harbouring clinical enterococci. The emergence of erm (T)-mediated erythromycin resistance among enterococci, potentially transferable to other nosocomial pathogens, should be constantly monitored.

The 5-Item Modified Frailty Index (mFI-5) for risk stratification of patients with infective endocarditis undergoing cardiac surgery

Abstract Background population aging has led to an increased burden of frailty as an emerging global health issue, and variables for its quantification in patients with infective endocarditis (IE) are lacking in current surgical risks scores. The 5-item modified frailty index (mFI-5) score has shown to be effective in the prediction of surgical outcomes in other medical scenarios. Purpose this study aimed to assess the role of the mFI-5 in the prediction of surgical outcomes in patients with left-sided IE undergoing cardiac surgery. Methods a total of 112 cases of confirmed left-sided IE undergoing surgery, were consecutively collected and followed during one year after diagnosis in two tertiary hospitals between 2016 and 2021. The mFI-5 score included 5 baseline patient-specific comorbidities: diabetes, congestive heart failure, non-independent functional status (Barthel index <80), hypertension and chronic obstructive pulmonary disease (range 0-5), and patients were categorised as mFI-low (<2, n=65), and mFI-high (>=2, n=47). Results mean age was 66 [SD 15] years, 67% were men and community-acquired infections were 75%. As shown in Table 1, mFI-high patients were older and, aside from the specific comorbidities included in the score, with more chronic kidney disease. The most isolated pathogen was S. viridans (n=32), predominantly in mFI-low, in contrast to enterococcal and polymicrobial IEs, which were more frequent in mFI-high. Larger vegetations were reported in mFI-high [16 (10) vs 13 (9) mm, p 0.03], with no differences regarding infection site or periannular complications. Acute kidney injury, decompensated heart failure and higher natriuretic peptides were more common in mFI-high. Regarding mortality, in-hospital deaths were more frequent in mFI-high group. When analyzing mFI-score as a discrete variable, in-hospital mortality was associated with higher median scores values [2 (2) vs 1(1) points, p 0.02], being 2 points the optimal cutoff point for prediction [AUC 0.64 (95% CI 0.54-0.73), Fig.1A]. Among survivors who completed follow-up (n=82), rehospitalization and all-cause mortality rates in mFI-high exceeded those from mFI-low. Predictors of in-hospital and 1-year mortality were assessed by logistic regression (Fig. 1B), confirming the independent prognostic association of mFI-5-score in patients with IE undergoing surgery. Conclusions patients with IE undergoing cardiac surgery with higher mFI-5 scores were older, more predisposed to enterococcal and polymicrobial infections, and had a greater comorbidity burden with a more complicated clinical course. The mFI-score was independently associated with in-hospital mortality as well as rehospitalizations and 1-year mortality, positioning itself as an additional tool for risk stratification in this cluster of patients.Table 1Figure 1

Clinical management and outcomes of patients with infective endocarditis according to frailty status

Abstract Background infective endocarditis (IE) remains a severe condition associated with a remarkably high mortality in certain groups of patients Purpose the aim of this study was to compare both the clinical management and short and mid-term prognosis of patients with IE according to their frailty status. Methods: a total of 200 cases of confirmed IE were consecutively collected in two tertiary hospitals between September 2016 and February 2021, and prospectively followed during one year after diagnosis. Patients were categorised according to the 5-item FRAIL scale as: Group A (n=48), for scores >2, and Group B (n=152), for scores <=2. Results mean age was 70 [SD 15] years, 64% were men and community-acquired infections were 69%. Baseline and clinical data are shown in Table 1. Enterococci were more frequent in Group A, but no significant differences were found regarding infection site, presence of vegetations or periannular complications, time to diagnosis or length of stay. During hospitalization, acute heart failure, delirium and bronchoaspiration were more common among frail patients. Unlike 18F-FDG PET/CT, which was more frequently done in Group B (34 vs 17%, p 0.03), transesophageal echocardiography was similarly performed between groups (92 vs 97%, p 0.08). Less frail patients underwent cardiac surgery (42 vs 68%, p 0.001), with a larger proportion of inoperable patients despite meeting surgical criteria (29 vs 12%, p 0.002). In-hospital mortality was higher in Group A, both overall and by therapeutic strategies, except in those inoperable patients with surgical indication but treated conservatively, where mortality did not differ between groups. Among survivors who completed follow-up (n=144), although recurrence rates were similar, readmission (75 vs 35%, p <0.001) and all-cause mortality rates (36 vs 5%, p <0.001) in Group A exceeded those from Group B. Predictors of in-hospital and 1-year mortality were assessed by logistic regression (Fig. 1), confirming the independent prognostic role of baseline FRAIL score in patients with IE [OR 1.5 (1.2-2.3) and 2.0 (1.5-2.6), respectively, for every additional scale point]. Conclusions frail patients with IE were older, more prone to enterococcal infections and in-hospital complications and had greater comorbidity burden. Both PET/CT and cardiac surgery were less performed in this group, which was characterized by a higher predicted surgical risk, as well as a worse short and mid-term prognosis.

25 years of experience on the management of enterococcal infective endocarditis an observational study.

As they are effective and well tolerated, aminopenicillins are still the cornerstone for the treatment of enterococcal infections. Current treatment guidelines for infective endocarditis (IE) recommend combination treatments, which carry a higher risk of adverse effects and are based on limited in vitro and experimental data. The aim of this study was therefore to evaluate the treatments of enterococcal IE in real-life practice. A total of 4121 episodes of enterococcal bloodstream infections, occurring between 1994 and 2019, were screened for the evidence of IE. Baseline characteristics, risk factors for complicated infections and treatment information were assessed and analyzed using Cox regression analysis. Overall, 80 (3.9%) IE episodes were identified of which 78 were included in the final analysis. Treatment regimens in our cohort comprised aminopenicillin-monotherapy (n = 20), teicoplanin-monotherapy (n = 26), other monotherapies (OMT) (n = 8), as well as combinations of ampicillin plus daptomycin (n = 8), ampicillin plus gentamicin (n = 4) or other combinations (n = 9). Overall mortality at 28-days was low (9 of 75) and increased to (19 of 75) after 6-months. Frequency of moderate to severe valve regurgitation (p = 0.89), or signs of uncontrolled infection (p = 0.5) and vegetation size ≥ 10mm (p = 0.11) were similar in the treatment groups. None of the treatment groups was associated with increased hazard for IE-related mortality. This retrospective study complements previous evidence, demonstrating that monotherapy regimens may be a suitable and effective option for the treatment of IE and supports the need for a prospective evaluation of aminopenicillin-monotherapy for initial and subsequent therapy in these patients.

Sentinel Surveillance reveals phylogenetic diversity and detection of linear plasmids harboring vanA and optrA among enterococci collected in the United States.

Enterococcus faecalis and Enterococcus faecium are frequent causes of healthcare-associated infections. Antimicrobial-resistant enterococci pose a serious public health threat, particularly vancomycin-resistant enterococci (VRE), for which treatment options are limited. The Centers for Disease Control and Prevention's Division of Healthcare Quality Promotion Sentinel Surveillance system conducted surveillance from 2018 to 2019 to evaluate antimicrobial susceptibility profiles and molecular epidemiology of 205 E. faecalis and 180 E. faecium clinical isolates collected from nine geographically diverse sites in the United States. Whole genome sequencing revealed diverse genetic lineages, with no single sequence type accounting for more than 15% of E. faecalis or E. faecium. Phylogenetic analysis distinguished E. faecium from 19 E. lactis (previously known as E. faecium clade B). Resistance to vancomycin was 78.3% among E. faecium, 7.8% among E. faecalis, and did not occur among E. lactis isolates. Resistance to daptomycin and linezolid was rare: E. faecium (5.6%, 0.6%, respectively), E. faecalis (2%, 2%), and E. lactis (5.3%, 0%). All VRE harbored the vanA gene. Three of the seven isolates that were not susceptible to linezolid harbored optrA, one chromosomally located and two on linear plasmids that shared a conserved backbone with other multidrug-resistant conjugative linear plasmids. One of these isolates contained optrA and vanA co-localized on the linear plasmid. By screening all enterococci, 20% of E. faecium were predicted to harbor linear plasmids, whereas none were predicted among E. faecalis or E. lactis. Continued surveillance is needed to assess the future emergence and spread of antimicrobial resistance by linear plasmids and other mechanisms.IMPORTANCEThis work confirms prior reports of E. faecium showing higher levels of resistance to more antibiotics than E. faecalis and identifies that diverse sequence types are contributing to enterococcal infections in the United States. All VRE harbored the vanA gene. We present the first report of the linezolid resistance gene optrA on linear plasmids in the United States, one of which co-carried a vanA cassette. Additional studies integrating epidemiological, antimicrobial susceptibility, and genomic methods to characterize mechanisms of resistance, including the role of linear plasmids, will be critical to understanding the changing landscape of enterococci in the United States.

Activity of the Caged Xanthone Morellic Acid against Vancomycin-Resistant Enterococcus Infection by Targeting the Bacterial Membrane.

Vancomycin-resistant Enterococcus (VRE) is an important nosocomial opportunistic pathogen that is associated with multidrug resistance. Here, we demonstrate that morellic acid inhibits VRE by restoring its sensitivity to vancomycin and ampicillin with low drug resistance and efficient biofilm clearance effects. Morellic acid binds to inner membrane phospholipids, such as phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL) of VRE, such that the fluidity and proton-motive force (PMF) interfere with the damaged inner membrane, causing intracellular reactive oxygen species (ROS) accumulation and bacterial death. Transcriptional analyses supported this effect on inner membrane-related pathways such as fatty acid biosynthesis and glycerophospholipid metabolism. Moreover, morellic acid significantly eliminated residual bacteria in the spleen, liver, kidneys, and abdominal effusion in mice. Our findings indicate the potential applications of morellic acid as an antibacterial agent or adjuvant for treating VRE infections.

Trends in Enterococcus faecium Bacteremia: Exploring Risk Factors with Emphasis on Prior Antibiotic Exposure

Enterococcal bacteremia (EB) is on the rise both in Sweden and globally. While Enterococcus faecalis (E. faecalis) is susceptible to ampicillin and piperacillin/tazobactam (pip/taz), Enterococcus faecium (E. faecium) is not. Historically, most enterococcal infections have been caused by E. faecalis, but the epidemiology is changing with increasing recognition of enterococci as nosocomial pathogens and the emergence of resistance to commonly used antimicrobial agents. The use of pip/taz has increased dramatically in Sweden, but it is unknown if this has affected the relative incidence of E. faecalis/E. faecium bacteremia. Here, we investigate whether the number and proportion of E. faecium bacteremia (EfmB) cases have increased. Additionally, risk factors associated with EfmB with a focus on prior antibiotic exposure are analyzed. Medical journals of 360 patients with EB admitted to Sahlgrenska University Hospital are reviewed. The proportion of EfmB cases increased from 41% in 2015 to 51% in 2021. Hospital-acquired infection, previous exposure to pip/taz, and carbapenems are identified as independent risk factors for EfmB. There are considerable patient-related differences between the EfmB and EfsB groups, but there is no difference in mortality rates. In conclusion, the increasing proportion of EfmB cases is concerning and is seen parallel to the expanding use of pip/taz, one possible contributing factor. Our findings suggest that a cautious approach to antibiotic use is essential to prevent the spread of antibiotic-resistant bacteria.

Combinatory Effect of Nitroxoline and Gentamicin in the Control of Uropathogenic Enterococci Infections.

Enterococcus faecalis, responsible for a majority of human and nosocomial enterococcal infections, is intrinsically resistant to aminoglycoside antibiotics (such as gentamicin, GEN), which must be used in a combined therapy to be effective. Nitroxoline (NTX) is an old antibiotic, underused for decades, but rediscovered now in an era of growing antibiotic resistance. In this in vitro study, the types of interactions between NTX and GEN on 29 E. faecalis strains were analyzed with an aim to find synergistic antimicrobial and antiadhesion combinations. Transmission electron microscopy (TEM) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to analyze changes in cell morphology and bacterial proteome after monotreatments and combined treatments. The results showed the synergistic effect for six combinations on eight strains, including the ATCC29212, and an additive effect for most strains. Combinations causing a complete inhibition of adhesion were established. Cell membrane integrity was affected by NTX, while combined NTX/GEN treatment caused dramatic changes in cell morphology. Upregulation of the expression of many proteins was established, with some emerging only after combined treatment. The results strongly imply that NTX has the potential for use in combined therapy with GEN against enterococci and it could further provide a substantial contribution to an ongoing fight against antimicrobial resistance and nosocomial infections.

V-313.3: Vancomycin resistant enterococcus infection in multivisceral transplant and small bowel transplant recipients: A 10-year single center experience.

V-313.3: Vancomycin resistant enterococcus infection in multivisceral transplant and small bowel transplant recipients: A 10-year single center experience.

Pharmacokinetic/pharmacodynamic analysis of vancomycin in patients with Enterococcus faecium bacteraemia: a retrospective cohort study

ObjectivesThe trough concentration of vancomycin and the area under the concentration–time curve (AUC)/minimum inhibitory concentration (MIC) ratio are crucial in determining vancomycin efficacy against methicillin-resistant Staphylococcus aureus. However, the use...

Linezolid in enterococcal urinary tract infection: a multicentre study.

Few data have been published on the efficacy of linezolid in enterococcal urinary tract infection (e-UTI). The aims of this study were to describe the characteristics of patients with enterococci UTI treated with linezolid, and to evaluate the efficacy and the tolerance of linezolid treatment. An observational multicentre retrospective study was conducted in 5 hospitals in France. Patients were included if they met the following criteria: ≥18 years, clinical and microbiological criteria for enterococcal UTI and linezolid treatment > 48h. Primary outcome was clinical failure. Eighty-one patients were included between January 2015 and December 2021. The median age was 73.0 [64; 83] years and 47 (58%) were men. The median Charlson comorbidity index was 3.00 [2; 6]. E. faecium was reported in 65 (80%) cases and E. faecalis in 26 cases (32%). Polymicrobial infections occurred in 41 (51%) cases. No enterococci was resistant to vancomycin. Before linezolid prescription an empiric antimicrobial treatment was started in 48 (59%) cases and was effective against enterococci in 19/48 (39.5%) patients for a median of 3.5 days [2.0; 4.0]. The median duration of linezolid antibiotic treatment was 13 days [10; 14]. Three adverse events were reported, none were serious but one led to discontinuation of treatment. Treatment failure was reported in 2 cases (2.5%). This study provides evidence for efficacy and safety of linezolid in enterococcal UTI.

Loratadine Derivative Lo-7: A Weapon against Drug-Resistant Enterococcus and Streptococcal Infections.

The primary obstacles in the management of Enterococcus and Streptococcal infections are drug resistance and biofilm formation. Our study revealed that loratadine at a concentration of ≥25 μM exhibited significant inhibitory effects on biofilm formation in 167 clinical strains of Enterococcus faecalis and 15 clinical isolates of Streptococcus agalactiae, Streptococcus pyogenes, and Streptococcus pneumoniae. Additionally, the antibiofilm activity against E. faecalis and Streptococcal was demonstrated by several loratadine derivatives with altered side-chain carbamate moieties. This study investigated the antibacterial activity of the loratadine derivative Lo-7 against clinical strains of S. agalactiae and S. pyogenes, with minimum inhibitory concentrations ranging from 12.5 to 25 μM. The findings revealed that a low concentration of loratadine derivative Lo-7 (3.125 μM) significantly augmented the bactericidal efficacy of vancomycin against multidrug-resistant (MDR) S. agalactiae, both in vitro and in vivo. The loratadine derivative Lo-7, even at low concentrations, demonstrated significant efficacy in eliminating intracellular MDR S. agalactiae within macrophages, potentially indicating a unique advantage over vancomycin, linezolid, and loratadine. Mechanistically, exposure to the loratadine derivative Lo-7 resulted in membrane depolarization without affecting membrane permeability in S. agalactiae. The potential targeting of the SecG subunit of the SecYEG membrane-embedded channel by the loratadine derivative Lo-7 in S. agalactiae was identified through quantitative proteomics, a drug affinity responsive target stability assay, and molecular docking.

Characterization and Anti-Biofilm Activity of Lytic Enterococcus Phage vB_Efs8_KEN04 against Clinical Isolates of Multidrug-Resistant Enterococcus faecalis in Kenya.

Enterococcus faecalis (E. faecalis) is a growing cause of nosocomial and antibiotic-resistant infections. Treating drug-resistant E. faecalis requires novel approaches. The use of bacteriophages (phages) against multidrug-resistant (MDR) bacteria has recently garnered global attention. Biofilms play a vital role in E. faecalis pathogenesis as they enhance antibiotic resistance. Phages eliminate biofilms by producing lytic enzymes, including depolymerases. In this study, Enterococcus phage vB_Efs8_KEN04, isolated from a sewage treatment plant in Nairobi, Kenya, was tested against clinical strains of MDR E. faecalis. This phage had a broad host range against 100% (26/26) of MDR E. faecalis clinical isolates and cross-species activity against Enterococcus faecium. It was able to withstand acidic and alkaline conditions, from pH 3 to 11, as well as temperatures between -80 °C and 37 °C. It could inhibit and disrupt the biofilms of MDR E. faecalis. Its linear double-stranded DNA genome of 142,402 bp contains 238 coding sequences with a G + C content and coding gene density of 36.01% and 91.46%, respectively. Genomic analyses showed that phage vB_Efs8_KEN04 belongs to the genus Kochikohdavirus in the family Herelleviridae. It lacked antimicrobial resistance, virulence, and lysogeny genes, and its stability, broad host range, and cross-species lysis indicate strong potential for the treatment of Enterococcus infections.

High Serum S100A12 as a Diagnostic and Prognostic Biomarker for Severity, Multidrug-Resistant Bacteria Superinfection and Herpes Simplex Virus Reactivation in COVID-19.

Neutrophils are critical immune cells in severe coronavirus disease 2019 (COVID-19). S100 calcium-binding protein A12 (S100A12) is highly expressed in neutrophils during acute inflammation. The aim of this study was to evaluate serum S100A12 levels as a diagnostic and prognostic tool in COVID-19. Serum samples of patients with moderate and severe COVID-19 were collected during 2020 to 2024. Enzyme-linked immunosorbent assay was used to measure serum S100A12 levels in 63 patients with moderate COVID-19, 60 patients with severe disease and 33 healthy controls. Serum S100A12 levels were elevated in moderate COVID-19 compared to controls and were even higher in severe cases. In moderate disease, serum S100A12 levels positively correlated with immune cell counts. While C-reactive protein and procalcitonin are established inflammation markers, they did not correlate with serum S100A12 levels in either patient cohort. Patients with severe COVID-19 and vancomycin-resistant enterococcus (VRE) infection had increased S100A12 levels. Elevated S100A12 levels were also observed in patients with herpes simplex reactivation. Fungal superinfections did not alter S100A12 levels. These data show that serum S100A12 increases in moderate and severe COVID-19 and is further elevated by VRE bloodstream infection and herpes simplex reactivation. Therefore, S100A12 may serve as a novel biomarker for severe COVID-19 and an early diagnostic indicator for bacterial and viral infections.

Risk Factors for 30-Day Mortality in Nosocomial Enterococcal Bloodstream Infections.

Enterococci commonly cause nosocomial bloodstream infections (BSIs), and the global incidence of vancomycin-resistant enterococci (VRE) BSIs is rising. This study aimed to assess the risk factors for enterococcal BSIs and 30-day mortality, stratified by Enterococcus species, vancomycin resistance, and treatment appropriateness. We conducted a retrospective cohort study (2014-2021) including all hospitalized adult patients with at least one blood culture positive for Enterococcus faecalis or Enterococcus faecium. We included 584 patients with enterococcal BSI: 93 were attributed to vancomycin-resistant E. faecium. The overall 30-day mortality was 27.5%; higher in cases of BSI due to vancomycin-resistant E. faecium (36.6%) and vancomycin-sensitive E. faecium (31.8%) compared to E. faecalis BSIs (23.2%) (p = 0.016). This result was confirmed by multivariable Cox analysis. Independent predictors of increased mortality included the PITT score, complicated bacteremia, and age (HR = 1.269, p < 0.001; HR = 1.818, p < 0.001; HR = 1.022, p = 0.005, respectively). Conversely, male gender, consultation with infectious disease (ID) specialists, and appropriate treatment were associated with reduced mortality (HR = 0.666, p = 0.014; HR = 0.504, p < 0.001; HR = 0.682, p = 0.026, respectively). In conclusion, vancomycin-resistant E. faecium bacteremia is independently associated with a higher risk of 30-day mortality.

Characteristics and outcomes of urinary tract infections caused by Enterococci: A multicenter retrospective study from two tertiary hospitals in Saudi Arabia

Enterococci are Gram-positive coccus bacteria that are normally present in the gastrointestinal tract and ordinarily function commensally with humans. Very few studies have investigated the characteristics of enterococcal infections. We aimed to characterize patients with urinary tract infections (UTIs) due to Enterococci and their outcomes. This was a retrospective cohort study between June 2012–November 2022. Patients who had clinically and microbiologically confirmed Enterococcal UTI based on a urine culture positive for E. faecalis or E. faecium with a count of ≥105 CFU/mL and having urinary tract symptoms were included. A total of 396 patients were eligible and included. The patients had a median age of 61 years and were mostly females (56.8 %). The most common characteristics were hospitalization in a non-ICU ward, having a urinary catheter, and recent use of antibiotics within the last 3 months (66.4 %, 59.3 %, and 51.8 %, respectively). Infection with E. faecalis was more common than E. faecium (77.3 % vs. 22.7 %). However, the latter exhibited higher rates of antibiotic resistance (P < 0.001 to several antibiotics) and was associated with significantly higher median C-reactive protein level (26.7 vs. 13 mg/dL; P = 0.025), mortality (23 % vs. 10.1 %; P = 0.002), and median length of stay (25 vs. 11.5 days; P < 0.001). We found that most patients with enterococcal UTIs had a history of having a urinary catheter and recent antibiotic use and were mostly females and hospitalized in non-ICU wards. E. faecium-infected patients experienced more severe episodes and poorer outcomes compared to patients infected with E. faecalis; thus, would need more aggressive therapy.

Draft genome sequences of clinical mastitis-associated Enterococcus faecalis and Enterococcus faecium carrying multiple antimicrobial resistance genes isolated from dairy cows

ObjectivesThe emergence of antimicrobial-resistant and mastitis-associated Enterococcus faecalis and Enterococcus faecium is of great concern due to the huge economic losses associated with enterococcal infections. Here we report the draft genome sequences of Enterococcus faecalis and Enterococcus faecium strains which were isolated from raw milk samples obtained from mastitis-infected cows in Bangladesh. MethodsStrains were isolated, identified and Genomic DNA was sequenced using Illumina NextSeq 550 platform. The assembled contigs were analyzed for virulence, antimicrobial resistance genes, and multi-locus sequence type. The genomes were compared to previously reported Enterococcus faecalis and Enterococcus faecium genomes to generate core genome phylogenetic trees. ResultsEnterococcus faecalis strain BR-MHR218Efa and Enterococcus faecium strain BR-MHR268Efe belonged to multilocus sequence type ST-190 and ST-22, respectively. Both sequence types seem to represent relatively rare sequence types. BR-MHR268Efe harbored only one antibiotic resistance gene encoding resistance towards macrolides (lsa(A)), while BR-MHR218Efa harbored ten different antibiotic resistance genes encoding resistance to aminoglycosides (ant[6]-Ia, aph(3′)-III), sulphonamides (aac(6′)-II), lincosamides (lnu(B)), macrolides (erm(B)), MLSB antibiotics (msr(C)), tetracyclines (tet(M), tet(L)), trimethoprim (dfrG) and pleuromutilin-lincosamide-streptogramin A (lsa(E)).The virulence gene composition was different in the two isolates. BR-MHR218Efa harbored only two virulence genes involved in adherence (acm, scm). BR-MHR268Efe harbored eight complete virulence operons including three operons involved in adherence (Ace, Ebp pili, EfaA), two operons involved in biofilm formation (BopD, Fsr) and three exoenzymes (gelatinase, hyaluronidase, SprE). ConclusionsThe genome sequences of strains BR-MHR268Efe and BR-MHR218Efa will serve as a reference point for molecular epidemiological studies of mastitis-associated Enterococcus faecalis and Enterococcus faecium. Additionally, the findings will help the understand the complex antimicrobial resistant livestock Enterococci.

The Impact of Enterococcus spp. in the Immunocompromised Host: A Comprehensive Review.

The immunocompromised host is usually vulnerable to infectious diseases due to broad-spectrum treatments and immunological dysregulation. The Enterococcus genus consists of normal gut commensals, which acquire a leading role in infective processes among individuals with compromised immune systems. These microorganisms may express a potential virulence and resistance spectrum, enabling their function as severe pathogens. The Enterococcus spp. infections in immunocompromised hosts appear to be difficult to resolve due to the immunological response impairment and the possibility of facing antimicrobial-resistant strains. As regards the related risk factors, several data demonstrated that prior antibiotic exposure, medical device insertion, prolonged hospitalization and surgical interventions may lead to Enterococcus overgrowth, antibiotic resistance and spread among critical healthcare settings. Herein, we present a comprehensive review of Enterococcus spp. in the immunocompromised host, summarizing the available knowledge about virulence factors, antimicrobial-resistance mechanisms and host-pathogen interaction. The review ultimately yearns for more substantial support to further investigations about enterococcal infections and immunocompromised host response.

Characteristics of Enterococcus species bloodstream infections among adults with and without onco-hematological malignancies: Experiences from the national center of Hungary.

Over the past decade, enterococcal bloodstream infection (BSI) shows increasing incidence globally among the elderly and in patients with comorbidities. In this study, we aimed to assess microbiological and clinical characteristics and long-term outcomes of BSIs caused by Enterococcus spp. in adult patients with and without active onco-hematological malignancies hospitalized at a national referral institute. A prospective analysis of consecutive enterococcal BSI cases was conducted in the National Institute of Hematology and Infectious Diseases (Budapest, Hungary) between December 2019 and April 2022. We compared characteristics and outcomes at 30-days and 1 year afterdiagnosis among patients with and without onco-hematological malignancies. In total, 141patients were included (median age 68 ± 21 years, female sex 36.9%), 37% (52/141) had active onco-hematological malignancies. The distribution of species was as follows: 50.4% Enterococcus faecalis, 46.1% Enterococcus faecium, 1.4% Enterococcus avium and Enterococcus gallinarum, and 0.7% Enterococcus raffinosus. No statistically significant differences in all-cause mortality rates were observed between patient subgroups at 30 days (32.7 vs. 28.1%; P = 0.57) and 1 year (75.0 vs. 60.7%; P = 0.09). Enterococcal bloodstream infections yielded a relevant burden of morbidity, but with nostatistical difference in long-term outcomes of adult patients with and without active onco-hematological malignancies.