Le Infezioni in Medicina, n. 4, 425-428, 2023

doi: 10.53854/liim-3104-1

EDITORIAL

Did the updated Duke criteria missed Erysipelothrix rhusiopathiae from the list of typical microorganisms causing infective endocarditis?

Lorenzo Volpicelli, Alessandra Oliva, Mario Venditti

Department of Public Health and Infectious Disease, Sapienza University of Rome, Italy

Article received 11 January 2023; accepted 25 October 2023

Corresponding author

Mario Venditti

E-mail: mario.venditti@uniroma1.it

SummaRY

Infectious endocarditis is a severe condition still characterized by a high morbidity and mortality rate. An early diagnosis may positively impact the outcome, so we need our diagnostic tools to match with the ever-changing epidemiologic and microbiologic landscape of infectious diseases.

We read with great interest the update to the Modified Duke Criteria for the diagnosis of Infectious Endocarditis recently proposed by the International Society for Cardiovascular Infectious Diseases and decided to propose the addition of Erysipelothrix rhusiopathiae to the list of typical microorganisms causing Endocarditis. This pathogen is widespread distributed in the world, has a zoonotic origin, harbors virulence factors and a multidrug resistance phenotype. Moreover, its retrieval from blood seems to have an important correlation with the presence of Endocarditis.

The inclusion of E. rhusiopathiae in the list of typical microorganisms may represent a further refinement of the Modified Duke Criteria, which represent a fundamental tool in the management of patients with suspected endocarditis.

Keywords: Erysipelothrix rhusiopathiae, Erysipeloid, Endocarditis, Modified Duke Criteria.

Infectious Endocarditis (IE) remains a severe condition with a high mortality rate where the prompt establishment of an adequate antibiotic therapy may improve the outcome [1]. Unfortunately, the formulation of an early diagnosis is getting more challenging due to the increasing age of occurrence, the evolving epidemiology, the misuse of antibiotics in the general population and the ever-growing prevalence of prosthetic devices [2]. Recently, the International Society for Cardiovascular Infectious Diseases (ISCVID) proposed a further update of the Modified Duke Criteria for IE diagnosis [3]. Among many relevant changes, ISCVID revised the list of typical microorganisms causing IE, defined as those pathogens whose isolation as bloodstream infection (BSI) agents is strongly associated with a concurrent IE, even if they do not represent a prevalent cause of IE [3]. Based on the high risk of IE in patients with bacteremia, S. lugdunensis, E. faecalis, Granulicatella, Abiotrophia and Gemella species and all Streptococcus species except for S. pneumoniae and S. pyogenes are now considered typical; on the contrary, non-faecalis Enterococci were omitted. Moreover, the new definitions consider the clinical context in which the episode of bacteremia occurs, and hence some pathogens are now typical only in the setting of intracardiac prosthetic material [3]. Considering these assumptions, we suggest the inclusion of Erysipelothrix rhusiopathiae in the new list of typical IE agents.

E. rhusiopathiae is a pleomorphic Gram-positive bacillus that ubiquitously contaminates soil and water and persist for a long period of time in the environment, including marine locations [4]. It is responsible for an erysipelas-like syndrome in wild and farm animals, possibly progressing to arthritis, sepsis, and IE. Substantial economic losses are associated with swine, turkey, and chicken erysipelas and with sheep polyarthritis [4]. In humans produces an occupational skin infection typical of livestock and seafood handlers, named erysipeloid, which manifests predominantly on hands as a superficial, inflammatory, painful, violaceous plaque usually self-limiting within 3-4 weeks without specific therapy [5]. Occasionally, the infection progresses causing a generalized cutaneous form and/or a systemic syndrome with BSI, hematogenous dissemination and possibly IE, that can take a fulminant course [5]. Endocarditis from E. rhusiopathiae appears to involve mainly native aortic and mitral valves, with a male predominance and alcohol abuse as a probable risk factor. Surgery is commonly required (about 57%) and the outcome of IE is frequently poor with a mortality rate of about 33% [6]. The evidence concerning the incidence of IE among patients with BSI from E. rhusiopathiae consists largely of case reports and case series, sometimes with conflicting results, while only 3 larger studies are available (Table 1). An early systematic review included 49 cases and stated that E. rhusiopathiae BSI may reveal the presence of an underlying IE with a very high likelihood (up to 90%) [5, 7]. This association was questioned by subsequent studies. A single-center retrospective study examined all cases of adults with E. rhusiopathiae BSI hospitalized in the previous 22 years. To be included patients required at least 2 simultaneous, positive blood cultures sets so that the numerosity obtained was very low (N=5). Finally, only 20% of subjects had ultrasound documented IE, but interestingly all the patients required 4-6 weeks of treatment to resolve symptoms [8]. A recent 20-year systematic review analyzed 62 cases of infections from E. rhusiopathie, the majority involving adult men with an animal-related job and living in a high-income country. Hypertension, diabetes, and alcoholism were the main associated diseases. Skin lesions were the most common manifestations of infection (33,9%), followed by heart valve involvement that affected 37,1% of the cohort and 60,9% of them required valve replacement surgery [9].

Table 1 - Prevalence of infectious endocarditis in patients with Erysipelothrix rhusiopathiae infection

By comparison (Table 1), BSI from Staphylococcus aureus is complicated by IE in 18,2% of cases, from Enterococcus faecalis in 11,5% and from Streptococcus-like bacteria in about 5,7% [10-12]. In a large retrospective cohort study the overall prevalence of IE in patients with BSI from many Streptococcal species was 6,4%, with S. mutans and S. sanguinis displaying the higher rates (>30%) [13].

E. rhusiopathiae is also equipped with some important virulence factors: the release of neuraminidase causes vascular damage, a polysaccharide capsule protects from phagocytosis and some adherence proteins with specific endothelial affinity are involved in the establishment of biofilm [14]. In addition, conventional culture techniques present low yield for E. rhusiopathiae due to slow growth rate and frequent contamination, requiring molecular techniques to increase sensitivity and avoid false positive results [15, 16].

In vitro susceptibility studies identified penicillin, cephalosporin, and imipenem as the most bactericidal drugs [17]. Worryingly, E. rhusiopathie is intrinsically resistant to vancomycin, teicoplanin, cotrimoxazole, aminoglycosides and rifampicin, antimicrobials that are often included in the empirical treatment of severe Gram-positive infections and IEs, especially for β-lactam-intolerant patients [15, 17].

So far, thanks to its stable penicillin susceptibility, this pathogen elicited low concern, but in recent times the nightmare of resistance is giving prove of itself in the context of veterinary medicine. Two in vitro findings on isolates collected from outbreaks of septicemic erysipelas in birds showed how this pathogen is acquiring additional resistance to commonly used molecules. Samples from poultry proved resistance to penicillin G in 42% and to erythromycin in 76%, while isolates from geese were resistant to norfloxacin in 68% and tetracycline in 63% [18, 19].

In conclusion, E. rhusiopathiae is a worldwide distributed, zoonotic, intrinsically glycopeptide-resistant pathogen with the potential to develop a multidrug-resistant phenotype, that harbors some dangerous virulence factors and is able to cause a severe form of IE. We recognize that evidence is still limited in quality and require larger and systematic studies but, as things stand, its recovery from blood has a likelihood of endocardial involvement higher than many pathogens that are presently regarded as typical of IE. The inclusion of E. rhusiopathiae in the updated list of typical IE microorganisms of the Modified Duke Criteria may constitute a further refinement of this fundamental tool for the diagnosis and management of patients with suspected IE.

Funding

This work received no funding.

Conflict of interest

The authors declare no conflict of interest.

Author contributions

LV: original draft preparation, research and editing; AO: conceptualization, review and editing; MV: conceptualization, review and editing.

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