Treatment of Enterococcus faecalis Endocarditis: History
View Latest Version
Please note this is an old version of this entry, which may differ significantly from the current revision.
Contributor:
Francesco Nappi
,
Sanjeet Singh Avtaar Singh
,
Vikram Jitendra
,
Antonio Fiore

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.

  • infective endocarditis
  • Enterococcus faecalis
  • Enterococcus faecalis pili
  • biofilm

1. Introduction

Enterococcus faecalis is a bacterium commonly found in the human gastrointestinal and biliary tracts. Its pathogenic effect is responsible for a significant proportion of surgical-site, urinary-tract, and bloodstream infections. Similarly, Group D streptococci (e.g., Streptococcus gallolyticus, Streptococcus bovis), which have been reclassified as Enterococci spp., are recognised for their ability to facilitate infective endocarditis (IE) linked with gastrointestinal- and urogenital-tract disorders that utilise the portal venous system as a means of entrance [1][2][3][4][5][6]. Studies in molecular biology and clinical therapeutics supporting enterococcal IE have indicated that the pili’s role is relevant to greater bacterial aggression due to their biogenesis, host immune response, and resistance to antimicrobial therapy [7][8][9][10][11][12].
Research has shown that F pili have three key functions in bacterial mating: firstly, they initiate contact between mating pairs; secondly, they facilitate the transfer of genetic material; and lastly, they draw the mating cells into close contact, which boosts the fertility of the bacterial union [13][14]. This could partly clarify the involvement of E. faecalis as one of the causative pathogens of bacterial IE, which is responsible for high mortality rates and severe complications such as exacerbating congestive heart failure, glomerulonephritis, and septic embolism.
Current guidelines suggest treating enterococcal endocarditis with a combination of antimicrobials immediately after diagnosis in order to manage the infection medically. However, worries regarding the emergence of bacteria resistant to multiple antibiotics, including strains of enterococcus that are resistant to vancomycin, have created uncertainty around the best guideline-directed medical therapy (GDMT) by widening an increasing gap [15][16][17][18]. There is substantial epidemiological evidence that more than 20% of enterococci isolated from intensive care unit patients’ infections are resistant to vancomycin. This is supported by several studies [8][9][16].
The occurrence of IE caused by E. faecalis affects one third of patients over 70 years old [19][20][21][22][23], with projections indicating increasing frequency in the future due to longer life expectancy [22][23]. The highest rise in the incidence of IE worldwide is among the elderly population, with elderly patients at 4.6 times higher risk than the general population [19][23]. Factors that contribute to the promotion of IE include the high frequency of undiagnosed degenerative valvular disease, as well as an increase in invasive procedures and implanted medical devices. These factors may also impact the outcome of IE in elderly patients, who experience significantly higher morbidity and mortality rates compared to younger adults. However, international guidelines for treating IE in elderly patients lack recommendations due to limited evaluation, which hinders precise management guidance [24].
The risk of infection reoccurring after valve replacement for IE is still worrying. Therefore, there has been a long-standing debate about the best substitute for a valve in this case [2][6][17][18][24]. According to surgical dogma, autologous or allogeneic tissue is the preferred choice over synthetic materials in an infected field that contains 60% gram-positive cocci (GPC). Given the reluctance to use foreign artificial materials, such as mechanical xenograft valve prosthetics or conventional stents, cardiac surgeons have preferred the use of allogeneic tissue. This approach has been particularly effective in cases of prosthetic-valve endocarditis (PVE) and other complex and aggressive cardiac injuries, such as evolving root abscess and invasion of the intervalvular fibrosa causing bivalvular involvement (both aortic and mitral valves) and a higher risk of fistulisation in the left atrium. Reported benefits have been significant [2][6][24].

2. Pathophysiology of E. faecalis Endocarditis

The initial query is what classifies E. faecalis as a pathogen. In fact, the pathogenic action of E. faecalis is distinct in its execution. Unlike group A streptococci or Staphylococcus aureus which are highly virulent pathogens that rely on the secretion of numerous hemolysins and toxins to effectively counteract innate immune responses [25][26], E. faecalis employs a lesser number of virulence factors for pathogenesis [11]. Emerging evidence indicates that the initial stage of E. faecalis infection is primarily initiated by attaching and colonising the surfaces of host tissue [7][11].
Supporting this hypothesis, scholars detected predominantly gram-positive pathogens, indicating the important function played by proteins in the adhesive matrix molecules (MSCRAMM) family that may be potential targets for the development of new and effective immunotherapies [27]. Sillanpaa and colleagues [28] have identified 17 proteins from the E. faecalis V583 genome [12] possessing cell-wall-anchoring motifs and MSCRAMM-like structural features [12][28]. These proteins contain one or more segments of 150 to 500 amino acids, which have Ig-like folds that are typical of the MSCRAMM Ig family found in Staphylococcus aureus, as observed in studies [28][29]. The detection of antibodies in E. faecalis endocarditis patients’ sera that interact with some of these proteins provides a clear explanation that these antibodies are effectively expressed in vivo during the infection. The researchers observed that a large proportion of patients’ sera had particularly high titres against three of these proteins—EbpA, EbpB, and EbpC [28].
There is evidence to suggest that two protein adhesins, enterococcus surface protein (Esp) and collagen adhesion protein of E. faecalis (Ace), play a significant role in promoting the attachment of enterococcus to host tissues [30][31]. Additionally, the aggregation substance (AS) facilitates the aggregation of replicating bacteria [32], further complementing the work of these two proteins.
During enterococcal infections, the secretion of virulence factors that degrade tissue is of significant importance. Consistency in the presence of these factors is essential for optimal infection control. Protease expression regulation in Enterococci occurs through the quorum-sensing locus of regulators (fsr) in E. faecalis, which includes the fsrC sensory kinase, fsrA response regulator, and fsrB-derived autoinducer [12][33]. Carniol et al. [33] examined the pathogenic and biomolecular mechanisms following the creation of an infectious site that contains a certain amount of enterococci. The activation of protease secretion occurs through non-latent Fsr signalling. The subsequent stage is the development of a biofilm, facilitated by Esp, Ace, Fsr, and proteases. The authors noted that within the bacterial community formed and attached to the surface enclosed in an extracellular matrix, enterococci exhibit a slower growth rate, higher resistance to antibiotics, and a high frequency of lateral gene transfer [33]. Cytolysin is expressed during this phase, being a toxin secreted by enterococci, which is cytolytic in nature due to two peptides possessing modifications characteristic of lantibiotics. The latter is made up of thioether amino acids, which result from post-translational modification of precursors synthesised at the ribosomal level [34][35]. These peptides work together to break down several host cells, including polymorpho-nuclear leukocytes, which are a crucial part of the immune defense against E. faecalis infection [14].
Microbiologists have recently confirmed the presence of pili on the surface of various strains of gram-positive bacteria, including Streptococcus spp., Actinomyces spp., and Corynebacterium spp. [36][37][38][39]. The presence of adhesins on the tip of the pilus, as well as the major and minor subunits of the pilus, has been proven by investigators using antibodies as detection reagents [40]. The analysis conducted on the genome has detected the structural genes that encode the pilina subunits in C. diphtheriae and A. naeslundii. These genes are situated in close proximity to the genes that code for sortase-like enzymes [40][41][42].
Sortases function as transpeptidases in the cell wall envelope of gram-positive bacteria, like staphylococci, listeria, or bacilli. Their main role is to cleave selection signals of surface proteins, thereby blocking their C-terminal carboxyl group through amide bond formation [43][44]. Deleting the sortase or pilin subunit gene expression removes pili formation [40].
The importance of sortases in facilitating pilus assembly has been highlighted by their ability to generate transpeptide bonds between cleaved pilin precursors’ C-terminal carboxyl group and the amino group of lysine residues’ side chain in pilina motif sequences. This model allows for several predictions that significantly back the more aggressive nature of pathogens capable of processing it. Gram-positive pathogens are mainly involved, with their genomic sequences possessing gene clusters encoding sortase, as well as surface proteins with sorting signals and pilin motif sequences that produce pili [45]. This forecast has been supported by various studies focusing on the crucial role of pili in promoting the pathogenicity of enterococci [46], and identifying pili’s presence on the surface of group B streptococci or pneumococci [47][48].

2.1. Enterococcal Pili and Infective Endocarditis

Sillanpää and colleagues [28] identified three open reading frames, ef1091–ef1093, that showed sorting signals and pilin motif sequences. Patients infected with E. faecalis were found to have a higher frequency of antibodies against these proteins in their sera compared to uninfected control patients [28]. Nallapareddy and colleagues [46] advanced the research on f1091–ef1093 and Sortase C (srtC), demonstrating that these three open reading frames and srtC are constituents of an operon that encodes pili associated with endocarditis and biofilm formation (ebp). Using immunofluorescence electron microscopy, researchers found EbpA, EbpB, and EbpC pili present on the surface of E. faecalis. Biofilm assays revealed that mutants lacking pili were unable to form biofilms.
Similarly, Tendolkar and colleagues [49] recognised a cluster of surface protein and sortase genes implicated in the formation of biofilms, which also contained the biofilm enhancer in Enterococcus. Nevertheless, this study did not demonstrate the capacity of enterococci to create pili [49].

2.2. Lesion Development and Progression of Infective Endocarditis in Heart Structure

Enterococci act as causative pathogens, causing infectious foci with aggressive colonisation due to their unique biogenesis. Standardisation of language and adherence to specific units and metrics are crucial in understanding the severity of the ailments caused by these bacteria. Enterococcus faecalis is the most prominent strain, resulting in both native valvular endocarditis (NVE) and prosthetic valvular endocarditis (PVE) in elderly or chronically ill patients [1][2][3][5]. The lesions commonly exhibit progressive evolution, forming large abscess cavities that affect one or more valves. In the most aggressive forms of IE, extensive parts of the heart, such as the aortic root, the intervalvular fibrosa, and the heart trigones, are destroyed [50][51][52][53][54][55]. It is well established that the evolution of Enterococcus faecalis infection is caused by the increasing resistance that these pathogens often develop towards vancomycin, aminoglycosides, and ampicillin. This has been documented in numerous studies [8][9][12][49][56][57][58][59][60][61].
The normally resilient cardiac endothelium is susceptible to bacteremia during E. faecalis-induced IE associated with an underlying colon tumor. Following endothelial injury, inflammatory cytokines and tissue factors are released, resulting in fibronectin expression and the formation of a platelet-fibrin thrombus that promotes bacterial adhesion [36][38][62]. Endothelial damage occurs due to the presence of valvular sclerosis, rheumatic valvulitis, or direct bacterial activity, commonly in cases of IE caused by Staphylococcus aureus, strains of enterococcus spp. (such as E. faecalis, Group D streptococci S. gallolyticus, S. bovis), or Streptococcus viridans (including S. mutans, S. salivarius, S. anginosus, S. mitis, and S. sanguinis). 
The formation of a biofilm, consisting of layers of bacteria held in a matrix of polysaccharides and proteins, can aid in bacterial survival and increase resistance to antibiotics. This suggests that pili attached to sortase, previously discovered in Corynebacterium spp., Actinomyces spp., group A and group B streptococci, and pneumococci, may also contribute significantly to the development of enterococcal infections [63].

3. Imaging Criteria

Infective endocarditis is a complex condition with notable morbidity and a high mortality rate during hospitalisation. Management of IE requires a multidisciplinary approach, a dedicated Endocarditis Team, and prompt access to advanced imaging techniques. Early surgical intervention when deemed necessary can be beneficial in reducing in-hospital mortality [24][64]. Patients with infective endocarditis (IE) caused by E. faecalis should undergo a detailed assessment of symptoms and a transthoracic echocardiogram (TTE). This will primarily evaluate the development of vegetations affecting one or more leaflets, the extent of the infection in the heart and aorta components (such as the leaflet, annulus, trigones, intervalvular fibrous, left atrium, and aortic root), as well as the size and function of the left ventricle.
Echocardiography remains the primary imaging technique for detecting anatomical evidence of infective endocarditis [19][65][66][67]. It is also a crucial Major Criterion in the 2023 Duke-ISCVID IE Criteria. While valvular vegetation is the typical echocardiographic sign of infective endocarditis (IE), other complications affecting valvular leaflets (such as perforation or pseudoaneurysm), paravalvular structures (such as abscess or fistula), or prosthetic valves (like valvular dehiscence) can also signal IE [5][66]. Transthoracic echocardiography is less sensitive than transesophageal echocardiography (TEE) for diagnosing IE.
Therefore, transesophageal echocardiography (TEE) is generally necessary when infective endocarditis (IE) is suspected, particularly in cases involving prosthetic valves, cardiac devices, or suspected complications such as perforation, paravalvular lesions, fistula, and prosthetic-valve dehiscence [5][19][64][65][66][67].
TEE assesses abscess development and progression, and the mechanism and severity of valve regurgitation. It is noteworthy that TTE shows moderate sensitivity (75%) and specificity (over 90%) in the detection of vegetation that confirms suspected native valvular endocarditis, as observed in studies [64][65][67][68]. Patients who present negative or equivocal evidence of infection on TTE, yet possess a high clinical probability of IE, should undergo TEE given its sensitivity of more than 90%. 
For the assessment of developing lesions, TEE is superior to TTE in detecting significant cardiac issues such as abscess, leaflet perforation, and pseudo-aneurysm. As a result, in most cases, TEE should be performed even if TTE has already provided enough indications for a definitive diagnosis. Research suggests that in the case of suspected endocarditis in patients with prosthetic valves, the TTE’s sensitivity is inadequate, not exceeding 36–69%. Therefore, a TEE is frequently required. [64][65][67][68][69][70][71] The selection of TEE is crucial in the case of a heart-device infection [5][64][65][68][69][70]. 
Today, it is strongly recommended to complete the diagnostic procedure with a CT scan, an 18F-FDG-PET/CT, and a cardiac MRI. The ISCVID Working Group included cardiac computed tomography (CCT) as a supplementary imaging modality in the 2023 Duke-ISCVID IE Criteria. Although CCT’s capability to detect vegetations is inferior to that of echocardiography, it exhibits a greater sensitivity in detecting paravalvular lesions due to its enhanced spatial resolution [65][71][72][73].
Positron emission CT with 18F-fluorodeoxyglucose ([18F] FDG PET/CT) has been incorporated as an imaging modality in the 2023 Duke-ISCVID IE Criteria. [18F] FDG PET/CT surpasses the diagnostic shortcomings of echocardiography when prosthetic material is being evaluated [36], thus resulting in the reclassification of a substantial section of suspected PVE cases from “possible” to “definite” IE. Due to ongoing controversies surrounding the efficacy of [18F] FDG PET/CT in rejecting IE, the ISCVID Working Group is currently prioritising investigations into its positive predictive value. The addition of [18F] FDG PET/CT as a Major Criterion in the Duke Criteria is shown to have a significant improvement in identifying definite PVE (pooled sensitivity, 0.86 [0.81–0.89]; pooled specificity, 0.84 [0.79–0.88]) when compared to echocardiography alone [5][65][74]. [18F] FDG PET/CT holds particular significance in diagnosing cardiac infections in patients with intricate cardiac implants, like multiple prosthetic valves, combined aortic valves and grafts, and congenital heart disease [5][65][74][75][76][77].

4. Treatment Option at referral Centre for IE

Surgery is necessary for 40–50% of patients with IE [78]. Prior to the introduction of valve-repair procedures, valve replacement was the favoured option for severe valve regurgitation due to the likelihood of IE recurrence [64][79]. Valve replacement may be preferred in specific circumstances, including cases of advanced age, or when a combined or complex surgical procedure is required, involving complete tissue removal in cases of PVE. It may also be recommended in instances of extensive and harmful NVE when infectious fields encompass a significant portion of the damaged heart [24][64][78][80][81][82][83][84][85][86]. The latest treatments employ transcatheter-valve therapy (TVT) to treat structural heart disease, which has demonstrated itself as a secure and useful technique for many patients. However, it is preferable to limit its use to elderly patients with coexisting medical conditions.

The accomplishment of valve surgery for IE is based on four general principles. First, surgical procedures must ensure the complete removal of infectious vegetations, followed by the repair or replacement of one or more heart valves. Secondly, the full integrity of the cardiac structures should be restored. Thirdly, to prevent the relapse of infection, complete debridement of the infected tissue should be performed. Valve replacement with allogeneic or autologous tissue is recommended to restore full cardiac function. Finally, if a surgeon performs a valve repair, they must ensure that there is no more than a trace of mild valve regurgitation after completing the repair [55][64][79][80][81][82][83][84][85][86].

4.1. Shared Decision-Making in IE Caused by Enterococcus faecalis

E. faecalis-induced endocarditis often presents a severe clinical picture that requires urgent hospital admission to a referral centre for endocarditis treatment. Delaying surgical procedures is not advised, and patients with IE from E. faecalis may experience heart failure due to regurgitation or valve obstruction, which is the main indication for surgery. Reported evidence from historical cohorts has demonstrated that the consequence of delaying surgery beyond 24 h of hospital admission could be catastrophic. These patients could develop refractory pulmonary edema or cardiogenic shock, leading to a rapid deterioration in their clinical status [87][88].
The prevention of embolism is the second concern of E. faecalis IE driving surgery. This complication affects 25–50% of patients and can result in infarction of the end organs such as limbs, spleen, kidney, and coronary arteries. Stroke is the most frequent neurological complication, but embolic complications can arise in any vascular bed [64][85][89].
The onset of E. faecalis endocarditis on the right side of the heart could considerably increase the likelihood of emboli to the lungs or systemic circulation via a patent foramen ovale. The majority of emboli are observed within the first 2 weeks of diagnosis and the risk quickly diminishes once antibiotics treatment is initiated [90][91]. In cases of embolism resulting from IE caused by Staphylococcus aureus or E. faecalis, the vegetations that contribute to the embolic process are typically large (over 10 mm in length), highly mobile, and commonly found on the mitral valve [64][92]. Surgery may be necessary if emboli continue to occur, and patients display evidence of persistent threatening vegetations as shown by echocardiography. Surgery is now considered safe after an ischemic stroke and the recommended delay of at least one month to avoid cerebral hemorrhage has been reassessed and significantly reduced intervention times are now in place [64][85].
Managing E. faecalis-induced IE is particularly challenging after TAVI, given the complexity of diagnosis and decision-making in this patient group. Therefore, the considerations for managing this specific type of IE are even more vital. TAVI-IE is a newly emerging entity, which is distinctly different from standard aortic-valve surgery–IE in terms of clinical features, microbiology, risk factors, and outcomes [65][93]. Higher exposure to healthcare procedures, older age, higher rates of comorbidities, and technical factors linked to the procedure can lead to an increased risk of bacteremia, which may contribute to increased risk of TAVI-IE [65][94][95][96][97].
The exact role and timing of surgery are still debated. Currently, surgical intervention is only recommended after meticulous individual case analysis, and it is unclear which patients will benefit from surgery. TAVI-IE is also a technical challenge, mainly due to the stent frame’s adherence to the aorta (particularly for self-expandable TAVI) and mitral-aortic fibrosa removal, particularly in inflamed tissues. There is a consensus that there is no disparity in TAVI-IE incidence between the two types of TAVI prosthesis. Nonetheless, two studies indicate a greater prevalence of TAVI-IE and vegetations attached to the stent frame among patients who receive self-expandable prostheses [95][96].

4.2. The Use of Biological Substitutes in the Context of E. faecalis Infective Endocarditis

Surgery can be very challenging in cases of abscesses that develop in the aortic annulus due to the colonisation of E. faecalis. This colonisation often leads to detachment of the intervalvular fibrosa, involvement of the aortic root and fibrous trigones, as well as the formation of a left atrial fistula. The surface pili of E. faecalis attract mating cells, promoting bacterial union, and leading to the formation of abscess cavities which may invade large areas of the heart [34][38][46]. Furthermore, the growth and expansion of pili-dependent infectious fields in E. faecalis-induced IE results in lesions larger than 10 mm, affecting multiple valve leaflets and often causing a severe inflammatory response [3][10][11][46]. This inflammatory response also affects the perivalvular tissues, causing them to become extremely fragile. The annulus’ consistency, as well as that of the surrounding regions, cannot be relied upon for suturing [53][64][68][80][98][99].
Over the course of one year, the range of pathogens causing PVE is equivalent to that of NVE, with enterococcal spp. being predominantly present [5]. As indicated in the case report, the clinical presentation is frequently upheld by extraordinary and negative imaging outcomes, in addition to the not-so-evident Duke criteria [5][100][101]. The formation of root abscesses and progression to valve dehiscence is common, with up to 60% of patients experiencing this occurrence rate. Surgery is typically necessary and performed before the patient’s clinical condition declines within 48 h of diagnosis. The surgical procedure is frequently technically challenging and high-risk, and recurrent PVE rates can vary between 6% and 15% [78]. PVE mortality is exceedingly high, especially when it is caused by S aureus, in comparison to enterococcal spp. One-year mortality rates can reach 50% [80][98][102][103].
To prevent infection recurrence caused by S. aureus and E. faecalis colonies, a biological substitute such as an aortic homograft or another full root xenograft is recommended for these patients. However, the clinical effectiveness of using an aortic homograft in the field of IE remains uncertain due to the absence of RCTs [93][98][104][105][106][107][108][109][110]. 
It is worth noting that no significant disparities in overall mortality and recurrence of infection have been reported when comparing conventional mechanical and biological substitutes in IE [98][104][105]. Klieverik and his team [108] found that patients who received homografts had a similar rate of recurrent endocarditis compared to those with mechanical valves, but with a lower freedom from reoperation (76% vs. 93%, respectively). 
These patients were managed with aortic homografts and experienced a freedom from recurrent infection rate of 95% at over two years, and an operative mortality rate of 3.9%. Fukushima et al. [106] found reinfection rates of just 0.2% at 30 days, but 5.5% of patients suffered from late infections at a median time of 5 years (ranging from 4 months to 16 years) after allograft implantation. Arabkhani and colleagues [107] reported favourable outcomes 27 years postoperatively utilising aortic homografts, with a low reoperation rate for recurring infections (2.2%). Allogeneic tissues demonstrated favourable responses to antibiotic treatment, effective in 21–25% of cases [93][98].
The use of allogeneic tissues in severe heart infections, whether in natural or artificial valves, is endorsed by Steffen et al. [111]. Post-implantation, the allogenic tissue exhibited a notable anti-bacterial effect, even after a storage period of five years. Antibiotic combinations administered during allograft treatment suggest a substantial impact on their resistance to infection. Tests conducted on ascending aortic homograft tissue have shown a significant increase in resistance to staphylococcal and enterococcal bacteria (Enterococcus faecalis and S. aureus), with lower bacterial contamination compared to homograft aortic valves. Kuhen and colleagues [112] proposed that administering antibiotics after thawing an allograft can significantly reduce infection recurrence, a benefit not yet demonstrated with conventional prostheses or Dacron grafts. However, using antibiotics to pretreat the prosthesis can reduce the risk of vascular-graft infection. The mechanism for this beneficial action and its potential interaction with pili function in E. faecalis-induced IE are unknown.

5. Conclusions

It is highly recommended to include molecular biology knowledge in conjunction with microbiology in the shared decision-making process alongside microbiological specialists. Intravenous combination therapy is generally preferred over monotherapy to minimise resistance and offer antimicrobial synergy [113]. Currently, there is encouraging laboratory data but limited clinical evidence to support the use of combination beta-lactam therapy for this indication. Further research is needed to determine the potential benefits of combining beta-lactam therapy contrasted with monotherapy to treat Gram-positive blood infections. Nonetheless, in cases of bacteremia unresponsive to standard antibiotic treatment, combining therapy may be advantageous [113]. The only exceptions are S. aureus and E. faecalis, as they are vulnerable to methicillin. Other treatment options for infections that have become resistant to vancomycin are obtainable, including linezolid, tigecycline, and daptomycin [114][115].

Given the rise in antibiotic resistance, there has been a growing interest in microbiological research that focuses on using bacterial factors as immunotherapeutic targets. This decision is based on the fact that bacterial factors play a significant role in an organism’s ability to colonise, infect, and ultimately cause disease [27]. MSCRAMMs have received significant attention recently due to their widespread presence and unique ability to promote the initiation of infections, including endocarditis [32], in both traditional and opportunistic pathogens [27][116]. Their central role in these processes is of particular interest. Unfortunately, complications have been identified in isolating and defining MSCRAMM from E. faecalis, which has yielded limited success due to this microorganism’s lack of adherence to ECM proteins in laboratory growth conditions [33][117]. This stands in contrast to its relatives, such as staphylococci and streptococci, which exhibit enhanced aggression.

To overcome this challenge, Sillanpa and colleagues utilised a bioinformatics method to identify multiple proteins that predict MSCRAMM-like structures [28]. By evaluating their reactivity with sera from E. faecalis-infected patients, the researchers concluded that some of these predicted proteins are indeed expressed by E. faecalis during infection. In particular, the study conducted by Sillanpa and colleagues [28], which examined antibodies in the sera of patients with E. faecalis endocarditis, identified nine recombinant forms of proteins anchored to the cell wall of E. faecalis. The authors noted three genes and a Sortase C (SrtC) gene, associated with sortase, which were expressed in vivo.

Research has shown that Enterococcus faecalis virulence is enhanced by cell-wall-linked proteins, such as sortase-mediated endocarditis and biofilm-linked pilus (Ebp), which play a crucial role in biofilm formation both in vitro and in vivo. Furthermore, a substantial body of contemporary literature has reported a rise in multi-drug resistance in the fight against Enterococcus faecalis infections. The creation of biofilms is a particular concern because it not only has the potential to protect drug-resistant organisms from antibiotics and opsonophagocytosis, but it can also increase horizontal gene transfer [33][118]. Previous studies on E. faecalis have demonstrated that various factors can significantly reduce the density of biofilms [57][58][59][60][61]. Disruption of esp, which encodes the surface protein of Enterococci in certain strains, promotes the latter. This promotion is facilitated by various factors including the fsr 2-component system, gelE which encodes for gelatinase, the Epa gene cluster which encodes for the polysaccharide Epa, and finally by atn which encodes for an autolysin or bopD sugar-binding transcriptional regulator [57][58][59][60][61].

This entry is adapted from the peer-reviewed paper 10.3390/microorganisms11102604

References

  1. Murray, B.E.; Weinstock, G.M. Enterococci: New aspects of an old organism. Proc. Assoc. Am. Physicians 1999, 111, 328–334.
  2. Richards, M.J.; Edwards, J.R.; Culver, D.H.; Gaynes, R.P. Nosocomial infections in combined medical-surgical intensive care units in the United States. Infect. Control Hosp. Epidemiol. 2000, 21, 510–515.
  3. Megran, D.W. Enterococcal endocarditis. Clin. Infect. Dis. 1992, 15, 63–71.
  4. Chirouze, C.; Athan, E.; Alla, F.; Chu, V.H.; Ralph Corey, G.; Selton-Suty, C.; Erpelding, M.L.; Miro, J.M.; Olaison, L.; Hoen, B.; et al. Enterococcal endocarditis in the beginning of the 21st century: Analysis from the International Collaboration on Endocarditis-Prospective Cohort Study. Clin. Microbiol. Infect. 2013, 19, 1140–1147.
  5. Fowler, V.G.; Durack, D.T.; Selton-Suty, C.; Athan, E.; Bayer, A.S.; Chamis, A.L.; Dahl, A.; Di Bernardo, L.; Durante-Mangoni, E.; Duval, X.; et al. The 2023 Duke-International Society for Cardiovascular Infectious Diseases Criteria for Infective Endocarditis: Updating the Modified Duke Criteria. Clin. Infect. Dis. 2023, 77, 518–526.
  6. Nappi, F.; Martuscelli, G.; Bellomo, F.; Avtaar Singh, S.S.; Moon, M.R. Infective Endocarditis in High-Income Countries. Metabolites 2022, 12, 682.
  7. Gilmore, M.S. The Enterococci: Pathogenesis, Molecular Biology, and Antibiotic Resistance; ASM Press: Washington, DC, USA, 2020; p. 439.
  8. Fridkin, S.K.; Gaynes, R.P. Antimicrobial resistance in intensive care units. Clin. Chest Med. 1999, 20, 303–316.
  9. Ammerlaan, H.S.; Harbarth, S.; Buiting, A.G.; Crook, D.W.; Fitzpatrick, F.; Hanberger, H.; Herwaldt, L.A.; van Keulen, P.H.; Kluytmans, J.A.; Kola, A.; et al. Secular trends in nosocomial bloodstream infections: Antibiotic-resistant bacteria increase the total burden of infection. Clin. Infect. Dis. 2013, 56, 798–805.
  10. Koch, S.; Hufnagel, M.; Theilacker, C.; Huebner, J. Enterococcal infections: Host response, therapeutic, and prophylactic possibilities. Vaccine 2004, 22, 822–830.
  11. Pillar, C.M.; Gilmore, M.S. Enterococcal virulence—Pathogenicity island of E. faecalis. Front. Biosci. 2004, 9, 2335–2346.
  12. Paulsen, I.T.; Banerjei, L.; Myers, G.S.; Nelson, K.E.; Seshadri, R.; Read, T.D.; Fouts, D.E.; Eisen, J.A.; Gill, S.R.; Heidelberg, J.F.; et al. Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus faecalis. Science 2003, 299, 2071–2074.
  13. Wang, Y.A.; Yu, X.; Ng, S.Y.; Jarrell, K.F.; Egelman, E.H. The structure of an archaeal pilus. J. Mol. Biol. 2008, 381, 456–466.
  14. Wang, Y.A.; Yu, X.; Silverman, P.M.; Harris, R.L.; Egelman, E.H. The structure of F-pili. J. Mol. Biol. 2009, 385, 22–29.
  15. Giessel, B.E.; Koenig, C.J.; Blake, R.L., Jr. Management of bacterial endocarditis. Am. Fam. Physician 2000, 61, 1725–1732.
  16. Gould, F.K.; Denning, D.W.; Elliott, T.S.; Foweraker, J.; Perry, J.D.; Prendergast, B.D.; Sandoe, J.A.; Spry, M.J.; Watkin, R.W. Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: A report of the Working Party of the British Society for Antimicrobial Chemotherapy. J. Antimicrob. Chemother. 2012, 67, 269–289.
  17. Cahill, T.J.; Baddour, L.M.; Habib, G.; Hoen, B.; Salaun, E.; Pettersson, G.B.; Schäfers, H.J.; Prendergast, B.D. Challenges in Infective Endocarditis. J. Am. Coll. Cardiol. 2017, 69, 325–344.
  18. Cahill, T.J.; Prendergast, B.D. Infective endocarditis. Lancet 2016, 387, 882–893.
  19. Bai, A.D.; Steinberg, M.; Showler, A.; Burry, L.; Bhatia, R.S.; Tomlinson, G.A.; Bell, C.M.; Morris, A.M. Diagnostic accuracy of transthoracic echocardiography for infective endocarditis findings using transesophageal echocardiography as the reference standard: A meta-analysis. J. Am. Soc. Echocardiogr. 2017, 30, 639–646.e8.
  20. Correa de Sa, D.D.; Tleyjeh, I.M.; Anavekar, N.S.; Schultz, J.C.; Thomas, J.M.; Lahr, B.D.; Bachuwar, A.; Pazdernik, M.; Steckelberg, J.M.; Wilson, W.R.; et al. Epidemiological trends of infective endocarditis: A population-based study in Olmsted County, Minnesota. Mayo Clin. Proc. 2010, 85, 422–426.
  21. Chen, H.; Zhan, Y.; Zhang, K.; Gao, Y.; Chen, L.; Zhan, J.; Chen, Z.; Zeng, Z. The Global, Regional, and National Burden and Trends of Infective Endocarditis from 1990 to 2019: Results from the Global Burden of Disease Study 2019. Front. Med. 2022, 9, 774224.
  22. Resende, P., Jr.; Fortes, C.Q.; do Nascimento, E.M.; Sousa, C.; Querido Fortes, N.R.; Thomaz, D.C.; de Bragança Pereira, B.; Pinto, F.J.; de Oliveira, G.M.M. In-hospital Outcomes of Infective Endocarditis from 1978 to 2015: Analysis Through Machine-Learning Techniques. CJC Open 2021, 4, 164–172.
  23. Allegranzi, B.; Bagheri Nejad, S.; Combescure, C.; Graafmans, W.; Attar, H.; Donaldson, L.; Pittet, D. Burden of endemic health-care-associated infection in developing countries: Systematic review and metaanalysis. Lancet 2011, 377, 228–241.
  24. Writing Committee Members; Otto, C.M.; Nishimura, R.A.; Bonow, R.O.; Carabello, B.A.; Erwin, J.P., 3rd; Gentile, F.; Jneid, H.; Krieger, E.V.; Mack, M.; et al. 2020 ACC/AHA Guideline for the Management of Patients with Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J. Am. Coll. Cardiol. 2021, 77, 450–500.
  25. Novick, R.P. Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol. Microbiol. 2003, 48, 1429–1449.
  26. Cunningham, M.W. Pathogenesis of group A streptococcal infections. Clin. Microbiol. Rev. 2000, 13, 470–511.
  27. Rivas, J.M.; Speziale, P.; Patti, J.M.; Hook, M. MSCRAMM-targeted vaccines and immu- notherapy for staphylococcal infection. Curr. Opin. Drug Discov. Dev. 2004, 7, 223–227.
  28. Sillanpaa, J.; Xu, Y.; Nallapareddy, S.R.; Murray, B.E.; Hook, M. A family of putative MSCRAMMs from Enterococcus faecalis. Microbiology 2004, 150, 2069–2078.
  29. Deivanayagam, C.C.; Wann, E.R.; Chen, W.; Carson, M.; Rajashankar, K.R.; Höök, M.; Narayana, S.V. A novel variant of the immunoglobulin fold in surface adhesins of Staphylococcus aureus: Crystal structure of the fibrin-ogen binding MSCRAMM, clumping factor A. EMBO J. 2002, 21, 6660–6672.
  30. Budzik, J.M.; Schneewind, O. Pili prove pertinent to enterococcal endocarditis. J. Clin. Investig. 2006, 116, 2582–2584.
  31. Shankar, V.; Baghdayan, A.S.; Huycke, M.M.; Lin-dahl, G.; Gilmore, M.S. Infection-derived Enterococcus faecalis strains are enriched in esp, a gene encoding a novel surface protein. Infect. Immun. 1999, 67, 193–200.
  32. Galli, D.; Wirth, R. Comparative analysis of Enterococcus faecalis sex pheromone plasmids identifies a single homologous DNA region which codes for aggregation substance. J. Bacteriol. 1991, 173, 3029–3033.
  33. Carniol, K.; Gilmore, M.S. Signal transduction, quorum-sensing, and extracellular protease activity in Enterococcus faecalis biofilm formation. J. Bacteriol. 2004, 186, 8161–8163.
  34. Coburn, P.S.; Gilmore, M.S. The Enterococcus faecalis cytolysin: A novel toxin active against eukaryotic and prokaryotic cells. Cell. Microbiol. 2003, 5, 661–669.
  35. Sahl, H.G.; Bierbaum, G. Lantibiotics: Biosynthesis and biological activities of uniquely modified peptides from gram-positive bacteria. Annu. Rev. Microbiol. 1998, 52, 41–79.
  36. Coburn, P.S.; Pillar, C.M.; Jett, B.D.; Haas, W.; Gilmore, M.S. Enterococcus faecalis senses target cells and in response expresses cytolysin. Science 2004, 306, 2270–2272.
  37. Yanagawa, R.; Honda, E. Presence of pili in species of human and animal parasites and pathogens of the genus Corynebacterium. Infect. Immun. 1976, 13, 1293–1295.
  38. Yeung, M.K. Actinomyces: Surface macromolecules and bacteria–host interactions. In Gram-Positive Pathogens; VFischetti, A., Novick, R.P., Ferretti, J.J., Portnoy, D.A., Rood, J.I., Eds.; American Society for Microbiology: Washington, DC, USA, 2000; pp. 583–593.
  39. Wu, H.; Fives-Taylor, P.M. Molecular strategies for fimbrial expression and assembly. Crit. Rev. Oral Biol. Med. 2001, 12, 101–115.
  40. Ton-That, H.; Schneewind, O. Assembly of pili on the surface of C. diphtheriae. Mol. Microbiol. 2003, 50, 1429–1438.
  41. Yeung, M.K.; Donkersloot, J.A.; Cisar, J.O.; Ragsdale, P.A. Identification of a gene involved in assembly of Actinomyces naeslundii T14V type 2 fimbriae. Infect. Immun. 1998, 66, 1482–1491.
  42. Li, T.; Khah, M.K.; Slavnic, S.; Johansson, I.; Stromberg, N. Different type I fimbrial genes and tropisms of commensal and potentially pathogenic Actinomyces spp. with different salivary acidic proline-rich protein and statherin ligand specificities. Infect. Immun. 2001, 69, 7224–7233.
  43. Mazmanian, S.K.; Liu, G.; Ton-That, H.; Schneewind, O. Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall. Science 1999, 285, 760–763.
  44. Ton-That, H.; Liu, G.; Mazmanian, S.K.; Faull, K.F.; Schneewind, O. Purification and characterization of sortase, the transpeptidase that cleaves surface proteins of Staphylococcus aureus at the LPXTG motif. Proc. Natl. Acad. Sci. USA 1999, 96, 12424–12429.
  45. Ton-That, H.; Schneewind, O. Assembly of pili in gram-positive bacteria. Trends Microbiol. 2004, 12, 251–261.
  46. Nallapareddy, S.R.; Singh, K.V.; Sillanpää, J.; Garsin, D.A.; Höök, M.; Erlandsen, S.L.; Murray, B.E. Endocarditis and biofilm-associated pili of Enterococcus faecalis. J. Clin. Investig. 2006, 116, 2799–2807.
  47. Lauer, P.; Rinaudo, C.D.; Soriani, M.; Margarit, I.; Maione, D.; Rosini, R.; Taddei, A.R.; Mora, M.; Rappuoli, R.; Grandi, G.; et al. Genome analysis reveals pili in Group B Streptococcus. Science 2005, 309, 105.
  48. Barocchi, M.A.; Ries, J.; Zogaj, X.; Hemsley, C.; Albiger, B.; Kanth, A.; Dahlberg, S.; Fernebro, J.; Moschioni, M.; Masignani, V.; et al. A pneumococcal pilus influences virulence and host inflammatory responses. Proc. Natl. Acad. Sci. USA 2006, 103, 2857–2862.
  49. Tendolkar, P.M.; Baghdayan, A.S.; Shankar, N. Putative surface proteins encoded within a novel transferable locus confer a high-biofilm phenotype to Enterococcus faecalis. J. Bacteriol. 2006, 188, 2063–2072.
  50. López, J.; Revilla, A.; Vilacosta, I.; Villacorta, E.; González-Juanatey, C.; Gómez, I.; Rollán, M.J.; San Román, J.A. Definition, clinical profile, microbiological spectrum, and prognostic factors of early-onset prosthetic valve endocarditis. Eur. Heart J. 2007, 28, 760–765.
  51. Alonso-Valle, H.; Fariñas-Alvarez, C.; García-Palomo, J.D.; Bernal, J.M.; Martín-Durán, R.; Gutiérrez Díez, J.F.; Revuelta, J.M.; Fariñas, M.C. Clinical course and predictors of death in prosthetic valve endocarditis over a 20-year period. J. Thorac. Cardiovasc. Surg. 2010, 139, 887–893.
  52. Nappi, F.; Singh, S.S.A.; Nappi, P.; Spadaccio, C.; Nenna, A.; Gentile, F.; Chello, M. Heart Valve Endocarditis. Surg. Technol. Int. 2020, 37, 203–215.
  53. Nappi, F.; Spadaccio, C. Simplest solutions are not always the cleverest: Can we stitch in an infected annulus? Should we rethink the current guidelines? J. Thorac. Cardiovasc. Surg. 2017, 154, 1899–1900.
  54. Nappi, F.; Spadaccio, C. keep fumbling around in the dark when it comes to infective endocarditis, or produce new, reliable data to redesign the guidelines? J. Thorac. Cardiovasc. Surg. 2018, 155, 75–76.
  55. Nappi, F.; Avtaar Singh, S.S.; Timofeeva, I. Learning from Controversy: Contemporary Surgical Management of Aortic Valve Endocarditis. Clin. Med. Insights Cardiol. 2020, 14, 1179546820960729.
  56. O’Toole, G.; Kaplan, H.B.; Kolter, R. Biofilm formation as microbial development. Annu. Rev. Microbiol. 2000, 54, 49–79.
  57. Mohamed, J.A.; Huang, W.; Nallapareddy, S.R.; Teng, F.; Murray, B.E. Influence of origin of isolates, especially endocarditis isolates, and various genes on biofilm formation by Enterococcus faecalis. Infect. Immun. 2004, 72, 3658–3663.
  58. Toledo-Arana, A.; Valle, J.; Solano, C.; Arrizubieta, M.J.; Cucarella, C.; Lamata, M.; Amorena, B.; Leiva, J.; Penadés, J.R.; Lasa, I. The enterococcal surface protein, Esp, is involved in Enterococcus faecalis biofilm formation. Appl. Environ. Microbiol. 2001, 67, 4538–4545.
  59. Hancock, L.E.; Perego, M. The Enterococcus faecalis fsr two-component system controls biofilm development through production of gelatinase. J. Bacteriol. 2004, 186, 5629–5639.
  60. Hufnagel, M.; Koch, S.; Creti, R.; Baldassarri, L.; Huebner, J. A putative sugar-binding transcriptional regulator in a novel gene locus in Enterococcus faecalis contributes to production of biofilm and prolonged bacteremia in mice. J. Infect. Dis. 2004, 189, 420–430.
  61. Kristich, C.J.; Li, Y.H.; Cvitkovitch, D.G.; Dunny, G.M. Esp-independent biofilm formation by Enterococcus faecalis. J. Bacteriol. 2004, 186, 154–163.
  62. Widmer, E.; Que, Y.A.; Entenza, J.M.; Moreillon, P. New concepts in the pathophysiology of infective endocarditis. Curr. Infect. Dis. Rep. 2006, 8, 271–279.
  63. Flemming, H.-C.; Wingender, J. The biofilm matrix. Nat. Rev. Microbiol. 2010, 8, 623–633.
  64. Avtaar Singh, S.S.; Costantino, M.F.; D’Addeo, G.; Cardinale, D.; Fiorilli, R.; Nappi, F. A narrative review of diagnosis of infective endocarditis-imaging methods and comparison. Ann. Transl. Med. 2020, 8, 1621.
  65. Delgado, V.; Ajmone Marsan, N.; de Waha, S.; Bonaros, N.; Brida, M.; Burri, H.; Caselli, S.; Doenst, T.; Ederhy, S.; Erba, P.A.; et al. 2023 ESC Guidelines for the management of endocarditis. Eur. Heart J. 2023, 44, 3948–4042.
  66. Behmanesh, B.; Gessler, F.; Schnoes, K.; Dubinski, D.; Won, S.Y.; Konczalla, J.; Seifert, V.; Weise, L.; Setzer, M. Infective endocarditis in patients with pyogenic spondylodiscitis: Implications for diagnosis and therapy. Neurosurg. Focus 2019, 46, E2.
  67. Habib, G.; Badano, L.; Tribouilloy, C.; Vilacosta, I.; Zamorano, J.L.; Galderisi, M.; Voigt, J.U.; Sicari, R.; Cosyns, B.; Fox, K.; et al. Recommendations for the practice of echocardiography in infective endocarditis. Eur. J. Echocardiogr. 2010, 11, 202–219.
  68. De Castro, S.; Cartoni, D.; d’Amati, G.; Beni, S.; Yao, J.; Fiorell, M.; Gallo, P.; Fedele, F.; Pandian, N.G. Diagnostic accuracy of transthoracic and multiplane transesophageal echocardiography for valvular perforation in acute infective endocarditis: Correlation with anatomic findings. Clin. Infect. Dis. 2000, 30, 825–826.
  69. Mihos, C.G.; Nappi, F. A narrative review of echocardiography in infective endocarditis of the right heart. Ann. Transl. Med. 2020, 8, 1622.
  70. Nappi, F.; Iervolino, A.; Singh, S.S.A. The New Challenge for Heart Endocarditis: From Conventional Prosthesis to New Devices and Platforms for the Treatment of Structural Heart Disease. Biomed. Res. Int. 2021, 2021, 7302165.
  71. Nappi, F.; Spadaccio, C.; Dreyfus, J.; Attias, D.; Acar, C.; Bando, K. Mitral endocarditis: A new management framework. J. Thorac. Cardiovasc. Surg. 2018, 156, 1486–1495.
  72. Khalique, O.K.; Veillet-Chowdhury, M.; Choi, A.D.; Feuchtner, G.; Lopez-Mattei, J. Cardiac computed tomography in the contemporary evaluation of infective endocarditis. J. Cardiovasc. Comput. Tomogr. 2021, 15, 304–312.
  73. Oliveira, M.; Guittet, L.; Hamon, M.; Hamon, M. Comparative value of cardiac CT and transesophageal echocardiography in infective endocarditis: A systematic review and meta-analysis. Radiol. Cardiothorac. Imaging 2020, 2, e190189.
  74. Wang, T.K.M.; Sánchez-Nadales, A.; Igbinomwanhia, E.; Cremer, P.; Griffin, B.; Xu, B. Diagnosis of infective endocarditis by subtype using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography: A contemporary meta- analysis. Circ. Cardiovasc. Imaging 2020, 13, e010600.
  75. Nappi, F.; Spadaccio, C.; Moon, M.R. A management framework for left sided endocarditis: A narrative review. Ann. Transl. Med. 2020, 8, 1627.
  76. Benedetto, U.; Spadaccio, C.; Gentile, F.; Moon, M.R.; Nappi, F. A narrative review of early surgery versus conventional treatment for infective endocarditis: Do we have an answer? Ann. Transl. Med. 2020, 8, 1626.
  77. Nappi, F.; Singh, S.S.A.; Spadaccio, C.; Acar, C. Revisiting the guidelines and choice the ideal substitute for aortic valve endocarditis. Ann. Transl. Med. 2020, 8, 952.
  78. Prendergast, B.D.; Tornos, P. Surgery for infective endocarditis: Who and when? Circulation 2010, 121, 1141–1152.
  79. David, T.E. Aortic valve repair for active infective endocarditis. Eur. J. Cardiothorac. Surg. 2012, 42, 127–128.
  80. Navia, J.L.; Elgharably, H.; Hakim, A.H.; Witten, J.C.; Haupt, M.J.; Germano, E.; Houghtaling, P.L.; Bakaeen, F.G.; Pettersson, G.B.; Lytle, B.W.; et al. Long-term Outcomes of Surgery for Invasive Valvular Endocarditis Involving the Aortomitral Fibrosa. Ann. Thorac. Surg. 2019, 108, 1314–1323.
  81. Paul, G.; Ochs, L.; Hohmann, C.; Baldus, S.; Michels, G.; Meyer-Schwickerath, C.; Fätkenheuer, G.; Mader, N.; Wahlers, T.; Weber, C.; et al. Surgical Procedure Time and Mortality in Patients with Infective Endocarditis Caused by Staphylococcus aureus or Streptococcus Species. J. Clin. Med. 2022, 11, 2538.
  82. Grubitzsch, H.; Schaefer, A.; Melzer, C.; Wernecke, K.D.; Gabbieri, D.; Konertz, W. Outcome after surgery for prosthetic valve endocarditis and the impact of preoperative treatment. J. Thorac. Cardiovasc. Surg. 2014, 148, 2052–2059.
  83. Hussain, S.T.; Shrestha, N.K.; Gordon, S.M.; Houghtaling, P.L.; Blackstone, E.H.; Pettersson, G.B. Residual patient, anatomic, and surgical obstacles in treating active left-sided infective endocarditis. J. Thorac. Cardiovasc. Surg. 2014, 148, 981–988.
  84. Manne, M.B.; Shrestha, N.K.; Lytle, B.W.; Nowicki, E.R.; Blackstone, E.; Gordon, S.M.; Pettersson, G.; Fraser, T.G. Outcomes after surgical treatment of native and prosthetic valve infective endocarditis. Ann. Thorac. Surg. 2012, 93, 489–493.
  85. Samura, T.; Yoshioka, D.; Toda, K.; Sakaniwa, R.; Yokoyama, J.; Suzuki, K.; Miyagawa, S.; Yoshikawa, Y.; Hata, H.; Takano, H.; et al. Emergency valve surgery improves clinical results in patients with infective endocarditis complicated with acute cerebral infarction: Analysis using propensity score matching †. Eur. J. Cardiothorac. Surg. 2019, 56, 942–949.
  86. Eranki, A.; Wilson-Smith, A.R.; Ali, U.; Saxena, A.; Slimani, E. Outcomes of surgically treated infective endocarditis in a Western Australian population. J. Cardiothorac. Surg. 2021, 16, 349.
  87. Richardson, J.V.; Karp, R.B.; Kirklin, J.W.; Dismukes, W.E. Treatment of infective endocarditis: A 10-year comparative analysis. Circulation 1978, 58, 589–597.
  88. Croft, C.H.; Woodward, W.; Elliott, A.; Commerford, P.J.; Barnard, C.N.; Beck, W. Analysis of surgical versus medical therapy in active complicated native valve infective endocarditis. Am. J. Cardiol. 1983, 51, 1650–1655.
  89. Thuny, F.; Di Salvo, G.; Belliard, O.; Avierinos, J.F.; Pergola, V.; Rosenberg, V.; Casalta, J.P.; Gouvernet, J.; Derumeaux, G.; Iarussi, D.; et al. Risk of embolism and death in infective endocarditis: Prognostic value of echocardiography: A prospective multicenter study. Circulation 2005, 112, 69–75.
  90. Vilacosta, I.; Graupner, C.; San Román, J.A.; Sarriá, C.; Ronderos, R.; Fernández, C.; Mancini, L.; Sanz, O.; Sanmartín, J.V.; Stoermann, W. Risk of embolization after institution of antibiotic therapy for infective endocarditis. J. Am. Coll. Cardiol. 2002, 39, 1489–1495.
  91. Dickerman, S.A.; Abrutyn, E.; Barsic, B.; Bouza, E.; Cecchi, E.; Moreno, A.; Doco-Lecompte, T.; Eisen, D.P.; Fortes, C.Q.; Fowler, V.G., Jr.; et al. ICE Investigators.The relationship between the initiation of antimicrobial therapy and the incidence of stroke in infective endocarditis: An analysis from the ICE Prospective Cohort Study (ICE-PCS). Am. Heart J. 2007, 154, 1086–1094.
  92. Chambers, H.F.; Bayer, A.S. Native-Valve Infective Endocarditis. N. Engl. J. Med. 2020, 383, 567–576.
  93. Savage, E.B.; Saha-Chaudhuri, P.; Asher, C.R.; Brennan, J.M.; Gammie, J.S. Outcomes and prosthesis choice for active aortic valve infective endocarditis: Analysis of the Society of Thoracic Surgeons Adult Cardiac Surgery Database. Ann. Thorac. Surg. 2014, 98, 806–814.
  94. Harding, D.; Cahill, T.J.; Redwood, S.R.; Prendergast, B.D. Infective endocarditis complicating transcatheter aortic valve implantation. Heart 2020, 106, 493–498.
  95. Regueiro, A.; Linke, A.; Latib, A.; Ihlemann, N.; Urena, M.; Walther, T.; Husser, O.; Herrmann, H.C.; Nombela-Franco, L.; Cheema, A.N.; et al. Association between transcatheter aortic valve replacement and subsequent infective endocarditis and in-hospital death. JAMA 2016, 316, 1083–1092.
  96. Mangner, N.; Woitek, F.; Haussig, S.; Schlotter, F.; Stachel, G.; Höllriegel, R.; Wilde, J.; Lindner, A.; Holzhey, D.; Leontyev, S.; et al. Incidence, Predictors, and Outcome of Patients Developing Infective Endocarditis Following Transfemoral Transcatheter Aortic Valve Replacement. J. Am. Coll. Cardiol. 2016, 67, 2907–2908.
  97. Amat-Santos, I.J.; Messika-Zeitoun, D.; Eltchaninoff, H.; Kapadia, S.; Lerakis, S.; Cheema, A.N.; Gutiérrez-Ibanes, E.; Munoz-Garcia, A.J.; Pan, M.; Webb, J.G.; et al. Infective endocarditis after transcatheter aortic valve implantation: Results from a large multicenter registry. Circulation 2015, 131, 1566–1574.
  98. David, T.E.; Gavra, G.; Feindel, C.M.; Regesta, T.; Armstrong, S.; Maganti, M.D. Surgical treatment of active infective endocarditis: A continued challenge. J. Thorac. Cardiovasc. Surg. 2007, 133, 144–149.
  99. Nappi, F.; Acar, C. Monobloc or Separate Aortic and Mitral Homografts for Endocarditis of the Intervalvular Fibrosa? Ann. Thorac. Surg. 2021, 112, 1382–1383.
  100. Pérez-Vázquez, A.; Fariñas, M.C.; García-Palomo, J.D.; Bernal, J.M.; Revuelta, J.M.; González-Macías, J. Evaluation of the Duke criteria in 93 episodes of prostheticvalve endocarditis: Could sensitivity be improved? Arch. Intern. Med. 2000, 160, 1185–1191.
  101. Chirouze, C.; Alla, F.; Fowler, V.G., Jr.; Sexton, D.J.; Corey, G.R.; Chu, V.H.; Wang, A.; Erpelding, M.L.; Durante-Mangoni, E.; Fernández-Hidalgo, N.; et al. ICE Prospective Investigators. Impact of early valve surgery on outcome of Staphylococcus aureus prostheticvalve infective endocarditis: Analysis in the International Collaboration of Endocarditis–Prospective Cohort Study. Clin. Infect. Dis. 2015, 60, 741–749.
  102. Wang, A.; Athan, E.; Pappas, P.A.; Fowler, V.G., Jr.; Olaison, L.; Paré, C.; Almirante, B.; Muñoz, P.; Rizzi, M.; Naber, C.; et al. International Collaboration on Endocarditis-Prospective Cohort Study Investigators. Contemporary clinical profile and outcome of prosthetic valve endocarditis. JAMA 2007, 297, 1354–1361.
  103. Nappi, F.; Nenna, A.; Petitti, T.; Spadaccio, C.; Gambardella, I.; Lusini, M.; Chello, M.; Acar, C. Long-term outcome of cryopreserved allograft for aortic valve replacement. J. Thorac. Cardiovasc. Surg. 2018, 156, 1357–1365.e6.
  104. Moon, M.R.; Miller, D.C.; Moore, K.A.; Oyer, P.E.; Mitchell, R.S.; Robbins, R.C.; Stinson, E.B.; Shumway, N.E.; Reitz, B.A. Treatment of endocarditis with valve replacement: The question of tissue versus mechanical prosthesis. Ann. Thorac. Surg. 2001, 71, 1164–1171.
  105. Kim, J.B.; Ejiofor, J.I.; Yammine, M.; Camuso, J.M.; Walsh, C.W.; Ando, M.; Melnitchouk, S.I.; Rawn, J.D.; Leacche, M.; MacGillivray, T.E.; et al. Are homografts superior to conventional prosthetic valves in the setting of infective endocarditis involving the aortic valve? J. Thorac. Cardiovasc. Surg. 2016, 151, 1239–1246.
  106. Fukushima, S.; Tesar, P.J.; Pearse, B.; Jalali, H.; Sparks, L.; Fraser, J.F.; Pohlner, P.G. Long-term clinical outcomes after aortic valve replacement using cryopreserved aortic allograft. J. Thorac. Cardiovasc. Surg. 2014, 148, 65–72.e62.
  107. Arabkhani, B.; Bekkers, J.A.; Andrinopoulou, E.R.; Roos-Hesselink, J.W.; Takkenberg, J.J.; Bogers, A.J. Allografts in aortic position: Insights from a 27-year, single-center prospective study. J. Thorac. Cardiovasc. Surg. 2016, 152, 1572–1579.e1573.
  108. Klieverik, L.M.; Yacoub, M.H.; Edwards, S.; Bekkers, J.A.; Roos-Hesselink, J.W.; Kappetein, A.P.; Takkenberg, J.J.; Bogers, A.J. Surgical treatment of active native aortic valve endocarditis with allografts and mechanical prostheses. Ann. Thorac. Surg. 2009, 88, 1814–1821.
  109. Sabik, J.F.; Lytle, B.W.; Blackstone, E.H.; Marullo, A.G.; Pettersson, G.B.; Cosgrove, D.M. Aortic root replacement with cryopreserved allograft for prosthetic valve endocarditis. Ann. Thorac. Surg. 2002, 74, 650–659.
  110. Jassar, A.S.; Bavaria, J.E.; Szeto, W.Y.; Moeller, P.J.; Maniaci, J.; Milewski, R.K.; Gorman, J.H., 3rd; Desai, N.D.; Gorman, R.C.; Pochettino, A. Graft selection for aortic root replacement in complex active endocarditis: Does it matter? Ann. Thorac. Surg. 2012, 93, 480–487.
  111. Steffen, V.; Marsch, G.; Burgwitz, K.; Kuehn, C.; Teebken, O.E. Resistance to infection of long-term cryopreserved human aortic valve allografts. J. Thorac. Cardiovasc. Surg. 2016, 151, 1251–1259.
  112. Kuehn, C.; Graf, K.; Mashaqi, B.; Pichlmaier, M.; Heuer, W.; Hilfiker, A.; Stiesch, M.; Chaberny, I.F.; Haverich, A. Prevention of early vascular graft infection using regional antibiotic release. J. Surg. Res. 2010, 164, 185–191.
  113. Bartash, R.; Nori, P. Beta-lactam combination therapy for the treatment of Staphylococcus aureus and Enterococcus species bacteremia: A summary and appraisal of the evidence. Int. J. Infect. Dis. 2017, 63, 7–12.
  114. Li, G.; Walker, M.J.; De Oliveira, D.M.P. Vancomycin Resistance in Enterococcus and Staphylococcus aureus. Microorganisms 2022, 11, 24.
  115. Rangama, S.; Lidbury, I.D.E.A.; Holden, J.M.; Borsetto, C.; Murphy, A.R.J.; Hawkey, P.M.; Wellington, E.M.H. Mechanisms Involved in the Active Secretion of CTX-M-15 β-Lactamase by Pathogenic Escherichia coli ST131. Antimicrob. Agents Chemother. 2021, 65, e0066321.
  116. Marston, H.D.; Dixon, D.M.; Knisely, J.M.; Palmore, T.N.; Fauci, A.S. Antimicrobial resistance. JAMA 2016, 316, 1193–1204.
  117. Guzman Prieto, A.M.; van Schaik, W.; Rogers, M.R.; Coque, T.M.; Baquero, F.; Corander, J.; Willems, R.J. Global emergence and dissemination of enterococci as nosocomial pathogens: Attack of the clones? Front. Microbiol. 2016, 7, 788.
  118. Parsek, M.R.; Singh, P.K. Bacterial bio-films: An emerging link to disease pathogenesis. Annu. Rev. Microbiol. 2003, 57, 677–701.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
This entry is offline, you can click here to edit this entry!
Video Production Service
Feedback