Search Results (22)

This review explores the biofilm architecture and drug resistance of Enterococcus faecalis in clinical and environmental settings. The biofilm in E. faecalis is a heterogeneous, three-dimensional, mushroom-like or multilayered structure, characteristically forming diplococci or short chains interspersed with water channels for nutrient exchange and waste removal. Exopolysaccharides, proteins, lipids, and extracellular DNA create a protective matrix. Persister cells within the biofilm contribute to antibiotic resistance and survival. The heterogeneous architecture of the E. faecalis biofilm contains both dense clusters and loosely packed regions that vary in thickness, ranging from 10 to 100 µm, depending on the environmental conditions. The pathogenicity of the E. faecalis biofilm is mediated through complex interactions between genes and virulence factors such as DNA release, cytolysin, pili, secreted antigen A, and microbial surface components that recognize adhesive matrix molecules, often involving a key protein called enterococcal surface protein (Esp). Clinically, it is implicated in a range of nosocomial infections, including urinary tract infections, endocarditis, and surgical wound infections. The biofilm serves as a nidus for bacterial dissemination and as a reservoir for antimicrobial resistance. The effectiveness of first-line antibiotics (ampicillin, vancomycin, and aminoglycosides) is diminished due to reduced penetration, altered metabolism, increased tolerance, and intrinsic and acquired resistance. Alternative strategies for biofilm disruption, such as combination therapy (ampicillin with aminoglycosides), as well as newer approaches, including antimicrobial peptides, quorum-sensing inhibitors, and biofilm-disrupting agents (DNase or dispersin B), are also being explored to improve treatment outcomes. Environmentally, E. faecalis biofilms contribute to contamination in water systems, food production facilities, and healthcare environments. They persist in harsh conditions, facilitating the spread of multidrug-resistant strains and increasing the risk of transmission to humans and animals. Therefore, understanding the biofilm architecture and drug resistance is essential for developing effective strategies to mitigate their clinical and environmental impact. Full article

Background: Ampicillin plus ceftriaxone (AC) is a first-line treatment for Enterococcus faecalis infective endocarditis (IE). Its administration in outpatient parenteral antibiotic treatment (OPAT) programs is challenging. The design of a ceftriaxone regimen suitable for OPAT requires deep knowledge of ceftriaxone pharmacokinetics (PK). Objective: We aim to explore ceftriaxone PK in elderly patients and propose dose regimens adapted to OPAT to maintain synergistic concentrations (Cs) with ampicillin against E. faecalis. Methods: We conducted a prospective observational pharmacokinetic study on patients (>55 years old) affected by E. faecalis IE. Ceftriaxone free concentration was measured at three time-points: before the administration (C_min) and two and four hours after ceftriaxone administration (C₂ and C₄). Both structural and covariate population pharmacokinetic models were built. Monte Carlo simulations of six ceftriaxone dosages were performed and the probability of target attainment (PTA) of an optimal Cs range was analyzed. The pharmacokinetic/pharmacodynamic index (PK/PD) to predict efficacy was defined as maintaining free ceftriaxone concentrations superior to the Cs at 50–100% of the dosing interval (fT ≥ Cs ≥ 50–100% of the dosing interval). Ceftriaxone dosing regimens were considered optimal if at least 90% of the simulated population was able to achieve the defined PK/PD targets. Results: Twenty-four episodes from 16 patients were included. Mean free ceftriaxone concentration pre-dose, +2 h, and +4 h were C_min = 7.8 ± 6.5 mg/L, C₂ = 34 ± 26.5 mg/L, and C₄ = 22.7 ± 19.7 mg/L, respectively. A two-compartment model with first-order absorption and elimination best described the data. Ceftriaxone one-hour infusions only achieved the minimum PK/PD target when the 2 g/12 h regimen was tested. On the other hand, ceftriaxone continuous infusion maintained a Cs above the PK/PD target for 100% of the dosing interval using ceftriaxone 4–6 g regimens. Conclusions: Our findings suggest that the optimal ceftriaxone exposure may be achieved using high-dose continuous infusions to ensure an ampicillin-killing effect when treating E. faecalis IE. Full article

Virulence attributes and putative antibiotic resistance genes from enterococcal isolates from wastewater treatment facilities for sustainable reuse and the areas where they discharge treated water were assessed using phenotypic and molecular methods. This analysis was performed on 269 Enterococci, of which 202 were vancomycin-resistant Enterococcus (VRE). VRE strains show markedly higher resistance across multiple antibiotics, especially glycopeptides and beta-lactams, compared to the more susceptible profile observed in vancomycin-susceptible Enterococcus (VSE) strains. vanC was found in every instance of E. gallinarum among VRE and enterococci susceptible to vancomycin (VSE) isolates but not in VR E. faecium/faecalis. Among VRE, 127 (62.9%) possessed at least one of the tetK, tetL, tetM, or tetO, while 22 (17.3%) had two of these genes. The multidrug efflux pump gene emeA was detected in 27 out of 202 (13.4%) VRE isolates and 8 out of 67 (11.9%) VSE isolates. Exactly 69 (78.4%) possessed at least one of the virulence determinants tested, with 10 (11.4%) and seven (8%) positive for haemolysis and gelatinase activity respectively. The gelatinase gene, gelE, was detected in 16 (18.1%) isolates, while more isolates (n = 23; 26.1%) were positive for gelatinase activity. Cytolytic (cyl) genes (1.1%), Angiotensin-converting-enzyme genes (ace) (13.6%), endocarditis-specific antigen A genes (efaA) (25%), hyaluronidase (hyl) genes (9.1%), enterococcal surface protein (esp) genes (4.5%), among others, were detected. Gelatinase activity and the amplified virulence genes were further validated by sequencing the gel-positive amplicons, which were almost identical (98.97%), and the gelE gene of Enterococcus sp. strain SQ07C was deposited under the GenBank accession number PQ381122. Overall, our results showed that the enterococcal isolates were considered as potential pathogens of notable threat to human health via exposure through reuse, and there is a need for more stringent treatment protocols. Full article

Background: While the relationship between recent dental treatment and the development of endocarditis is largely undisputed, the relationship between poor dental status and the development of infective endocarditis has not yet been proven beyond doubt. We have therefore analyzed this hypothetical connection using our established endocarditis register (B.E.R.). Patients and Methods: A total of 72 patients who underwent dental treatment (TREAT) and 55 patients with a desolate dental status (DESOLATE) were found in our database of 530 patients subsequently developing infective endocarditis necessitating valve surgery. A propensity score analysis was performed comparing TREAT as well as DESOLATE with matched patients without these conditions as CONTROL. Results: TREAT showed significantly more often Strept. mitis (26.9%) as well as other Streptococci (36.54%, p = 0.001) compared to CONTROL (3.51% and 10.53%, respectively), whereas Staphylococci and E. faecalis were found more often in CONTROL than in TREAT (S. aureus: 22.81% vs. 15.38%, n.s.; other Staphylococci 14.04% vs. 1.92%, p = 0.033; E. faec.: 26.32% vs. 9.62%, p = 0.045). DESOLATE showed significantly more Strept. mitis compared to CONTROL (27.91% vs. 4.88%, p = 0.007). Early mortality was 23.7% in the TREAT group, while it was 15.25% in the CONTROL group and 17.02% in the DESOLATE group vs. 20.83% in the CONTROL patients. Conclusions: The current results suggest that adequate endocarditis prophylaxis to prevent bacteremia may not be carried out in patients undergoing dental treatment and may occur spontaneously in patients with poor dental care. Both situations require new strategies to avoid such severe consequences. Full article

Background: Infective endocarditis is a severe, life-threatening condition which affects the endocardial lining of the heart. Right-sided IE typically affects the tricuspid valve and, less commonly, the pulmonary valve, often in association with intravenous drug use and intracardiac devices. Enterococcus faecalis, a significant pathogen in healthcare settings, is frequently resistant to several antibiotics, complicating treatment. Results: We present the case of a 69-year-old man diagnosed with isolated pulmonary valve endocarditis, with no identifiable risk factors, good oral hygiene, and no recent dental procedures. In our case, the E. faecalis strain, initially susceptible to ampicillin, acquired resistance during high-dose ampicillin and gentamicin therapy, leading to cardiac surgery and prolonged antibiotic treatment. Conclusions: IPE is rare, emphasizing the need for heightened clinical awareness and thorough diagnostic evaluation, especially in patients with endocarditis symptoms and known risk factors. Although ampicillin resistance in E. faecalis is uncommon, its emergence during treatment presents a challenge, necessitating careful antibiotic stewardship to improve outcomes. Full article

(1) Background: Alternative antibiotics are needed to treat infective endocarditis (IE) caused by non-faecalis/non-faecium enterococci; we aimed to assess the in vitro activity of ampicillin plus ceftriaxone (AMP + CTR) against these enterococci and to describe its clinical efficacy in IE cases. (2) Methods: Time–kill curves with standard (ISI) and high (IHI) inocula were performed to test VanC isolates [3 E. casseliflavus (ECAS) and 1 E. gallinarum (EGALL)] and non-VanC isolates [1 E. durans (EDUR), 1 E. hirae (EHIR) and 1 E. raffinosus (ERAF)]. The narrative literature review of IE cases treated with AMP + CTR was analyzed alongside three study cases. Clinical outcomes were relapse and death. (3) Results: Ampicillin plus gentamicin (AMP + GEN) showed synergistic and bactericidal activity against most isolates. AMP + CTR was synergistic at ISI for EGALL, EDUR, and EHIR and bactericidal against EHIR. At IHI, indifferent activity was observed for all isolates. In IE cases treated with AMP + CTR, it was only effective for EDUR and EHIR. Clinical information for EGALL IE is lacking. For IE caused by ECAS and ERAF, AMP + CTR seems suboptimal or ineffective, respectively. (4) AMP + CTR cannot be recommended for treating IE due to ECAS/ERAF. In contrast, this combination was effective in IE caused by EDUR/EHIR and could be recommended. Full article

(1) Background: Granulicatella adiacens is a former nutritionally variant streptococci (NVS). NVS infective endocarditis (IE) is generally characterized by a higher rate of morbidity and mortality, partially due to difficulties in choosing the most adequate microbiological culture method and the most effective treatment strategy, and partially due to higher rates of complications, such as heart failure, peripheral septic embolism, and peri-valvular abscess, as well as a higher rate of valve replacement. Depending on the affected valve (native valve endocarditisNVE, or prosthetic valve endocarditisPVE), the American Heart Association (AHA) 2015 treatment guidelines (GLs) suggest penicillin G, ampicillin, or ceftriaxone plus gentamicin (2 weeks for NVE and up to 6 weeks for PVE), while vancomycin alone may be a reasonable alternative in patients who are intolerant of β-lactam therapy. The European Society of Cardiology (ESC) 2023 GLs recommend treating NVE with penicillin G, ceftriaxone, or vancomycin for 6 weeks, suggesting combined with an aminoglycoside (AG) for at least the first 2 weeks only for PVE; likewise, the same recommendations for IE due to Enterococcus faecalis. (2) Methods: Starting from the case of a 51-year-old man with G. adiacens aortic bio-prosthesis IE who was successfully treated with aortic valve replacement combined with double beta-lactams, an AG-sparing regimen, we performed microbiology tests in order to validate this potential treatment change. (3) Results: As for E. faecalis IE, we found that the combination of ampicillin plus cephalosporines (like ceftriaxone or ceftobiprole) showed a synergistic effect in vitro, probably due to wider binding to penicillin-binding proteins (PBPs), thus contributing to enhanced bacterial killing and good clinical outcome, as well as avoiding the risk of nephrotoxicity due to AG association therapy. (4) Conclusions: Further studies are required to confirm this hypothesis, but double beta-lactams and an adequate sourcecontrol could be a choice in treating G. adiacens IE. Full article

Enterococcus faecalis is a bacterial pathogen that can cause opportunistic infections. Studies indicate that initial biofilm formation plays a crucial regulatory role in these infections, as well as in colonising and maintaining the gastrointestinal tract as a commensal member of the microbiome of most land animals. It has long been thought that vegetation of endocarditis resulting from bacterial attachment to the endocardial endothelium requires some pre-existing tissue damage, and in animal models of experimental endocarditis, mechanical valve damage is typically induced by cardiac catheterisation preceding infection. This section reviews historical and contemporary animal model studies that demonstrate the ability of E. faecalis to colonise the undamaged endovascular endothelial surface directly and produce robust microcolony biofilms encapsulated within a bacterially derived extracellular matrix. This report reviews both previous and current animal model studies demonstrating the resilient capacity of E. faecalis to colonise the undamaged endovascular endothelial surface directly and produce robust microcolony biofilms encapsulated in a bacterially derived extracellular matrix. The article also considers the morphological similarities when these biofilms develop on different host sites, such as when E. faecalis colonises the gastrointestinal epithelium as a commensal member of the common vertebrate microbiome, lurking in plain sight and transmitting systemic infection. These phenotypes may enable the organism to survive as an unrecognised infection in asymptomatic subjects, providing an infectious resource for subsequent clinical process of endocarditis. Full article

Enterococcus faecalis (E. faecalis) is a commensal bacterium that causes various infections in surgical sites, the urinary tract, and blood. The bacterium is becoming a significant concern because it tends to affect the elderly population, which has a high prevalence of undiagnosed degenerative valvular disease and is often subjected to invasive procedures and implanted medical devices. The bacterium’s actions are influenced by specific characteristics like pili activity and biofilm formation. This resistance significantly impedes the effectiveness of numerous antibiotic therapies, particularly in cases of endocarditis. While current guidelines recommend antimicrobial therapy, the emergence of resistant strains has introduced complexity in managing these patients, especially with the increasing use of transcatheter therapies for those who are not suitable for surgery. Presentations of the condition are often varied and associated with generalised symptoms, which may pose a diagnostic challenge. We share our encounter with a case study that concerns an octogenarian who had a TAVI valve and developed endocarditis. We also conducted a literature review to identify the essential treatment algorithms for such cases. Full article

E. faecalis has been associated with bacteremia, sepsis, and bacterial endocarditis and peri-implantitis. This microorganism can remain in the alveolus even after extraction of the root remnant. This study aimed to evaluate the corrosion on different surfaces of commercially pure titanium (Ti) grade 4 (Ticp-G4) as a function of the bacterial biofilm effect of Enterococcus faecalis. A total of 57 discs were randomly divided according to their surface finish (n = 19). For microbiological analysis (n = 9), the discs were placed in 12-well plates containing E. faecalis culture and incubated at 37 °C for 7 days. The results show that for the intergroup analysis, considering the “electrolyte” factor, there was a difference between the groups. There was greater biofilm formation for the D.A.Zir group, with greater electrochemical exchange for Biofilm, and the presence of biofilm favored greater electrochemical exchange with the medium. Full article

Background: Enterococcus faecalis is responsible for a large variety of severe infections. This study is a case series reporting our experience in the treatment of E. faecalis invasive infections with ampicillin in combination with ceftobiprole (ABPR). Methods: We retrospectively analyzed all the medical records of patients admitted to the University Hospital of Udine from January to December 2020 with a diagnosis of infective endocarditis or primary or non-primary complicated or uncomplicated bacteremia caused by E. faecalis. Results: Twenty-one patients were included in the final analysis. The clinical success rate was very high, accounting for 81% of patients, and microbiological cure was obtained in 86% of patients. One relapse was recorded in one patient who did not adhere to the partial oral treatment prescribed. Therapeutic drug monitoring (TDM) was always performed for ampicillin and ceftobiprole, and serum concentrations of both drugs were compared to the MICs of the different enterococcal isolates. Conclusions: ABPR is a well-tolerated antimicrobial regimen with anti-E. faecalis activity. TDM can help clinicians optimize medical treatments to achieve the best possible efficacy with fewer side effects. ABPR might be a reasonable option for the treatment of severe invasive infections caused by E. faecalis due to the high level of enterococcal penicillin-binding protein (PBP) saturation. Full article

Today, Enterococcus faecalis is one of the main causes of infective endocarditis in the world, generally affecting an elderly and fragile population, with a high mortality rate. Enterococci are partially resistant to many commonly used antimicrobial agents such as penicillin and ampicillin, as well as high-level resistance to most cephalosporins and sometimes carbapenems, because of low-affinity penicillin-binding proteins, that lead to an unacceptable number of therapeutic failures with monotherapy. For many years, the synergistic combination of penicillins and aminoglycosides has been the cornerstone of treatment, but the emergence of strains with high resistance to aminoglycosides led to the search for new alternatives, like dual beta-lactam therapy. The development of multi-drug resistant strains of Enterococcus faecium is a matter of considerable concern due to its probable spread to E. faecalis and have necessitated the search of new guidelines with the combination of daptomycin, fosfomycin or tigecycline. Some of them have scarce clinical experience and others are still under investigation and will be analyzed in this review. In addition, the need for prolonged treatment (6–8 weeks) to avoid relapses has forced to the consideration of other viable options as outpatient parenteral strategies, long-acting administrations with the new lipoglycopeptides (dalbavancin or oritavancin), and sequential oral treatments, which will also be discussed. Full article

Currently, ampicillin plus ceftriaxone (AC) is one of the preferred treatments for Enterococcus faecalis infective endocarditis. However, there is a lack of stability data for the combination of both drugs in elastomeric devices, so the inclusion of AC in Outpatient Parenteral Antimicrobial Therapy (OPAT) programs is challenging. The objective of the study was to determine the stability of AC in elastomeric pumps when stored at 8 ± 2 °C, 25 ± 2 °C, 30 ± 2 °C and 37 ± 2 °C using LC-MS/MS. The combination was diluted in 0.9% sodium chloride and the final concentrations were ampicillin 24 g/L plus ceftriaxone 8 g/L. Physical and chemical stability were evaluated at 12, 20, 24, 36 and 48 h after preparation. Stability was met at each time point if the percentage of intact drug was ≥90% of its respective baseline concentration and color and clearness remained unchanged. The drug combination was stable for 48 h when it was kept at 8 ± 2 °C. At 25 ± 2 °C and 30 ± 2 °C, they were stable for 24 h of storage. At 37 ± 2 °C, the stability criterion was not met at any time point. These results prove that AC could be included in OPAT programs using elastomeric infusion devices for the treatment of E. faecalis infections. Full article

Lactococcus garvieae causes infectious diseases in animals and is considered an emerging zoonotic pathogen involved in human clinical conditions. In silico analysis of plasmid pLG50 of L. garvieae Lg-Granada, an isolate from a patient with endocarditis, revealed the presence of two gene clusters (orf46–47 and orf48–49), each one encoding a novel putative bacteriocin, i.e., garvicin AG1 (GarAG1; orf46) and garvicin AG2 (GarAG2; orf48), and their corresponding immunity proteins (orf47 and orf49). The chemically synthesised bacteriocins GarAG1 and GarAG2 presented inhibitory activity against pathogenic L. garvieae strains, with AG2 also being active against Listeria monocytogenes, Listeria ivanovii and Enterococcus faecalis. Genetic organisation, amino acid sequences and antimicrobial activities of GarAG1 and GarAG2 indicate that they belong to linear non-pediocin-like one-peptide class IId bacteriocins. Gram-positive bacteria that were sensitive to GarAG2 were also able to ferment mannose, suggesting that this bacteriocin could use the mannose phosphotransferase transport system (Man-PTS) involved in mannose uptake as a receptor in sensitive strains. Intriguingly, GarAG1 and GarAG2 were highly active against their own host, L. garvieae Lg-Granada, which could be envisaged as a new strategy to combat pathogens via their own weapons. Full article

(1) Background: This paper aims to provide a description of non-faecalis non-faecium enterococci isolated from a tertiary care hospital in Romania and to briefly review the existing literature regarding the involvement of Enterococcus raffinosus, Enterococcus durans and Enterococcus avium in human infections and their antimicrobial resistance patterns; (2) Methods: We retrospectively analyzed all Enteroccocus species isolated from the “Prof. Dr. O. Fodor” Regional Institute of Gastroenterology and Hepatology from Cluj-Napoca during one year focusing on non-faecalis non-faecium Enterococci. A brief review of the literature was performed using case reports involving Enterococcus raffinosus, Enterococcus durans and Enterococcus avium; (3) Results: Only 58 out of 658 Enteroccocus isolates were non-faecalis non-faecium and met the inclusion criteria. These species were isolated more often (p < 0.05) from the surgical ward from mixed etiology infections with E. coli. In our review, we included 39 case reports involving E. raffinosus, E. durans and E. avium; (4) Conclusions: Isolation of non-faecalis non-faecium enterococci displays an emerging trend with crucial healthcare consequences. Based on the analysis of the case reports, E. avium seems to be involved more often in neurological infections, E. durans in endocarditis, while E. raffinosus displays a more heterogenous distribution. Full article