Destructive Erysipelothrix rhusiopathiae Endocarditis Confirmed on Valve Tissue Culture After Persistent Blood Culture Negativity

ABSTRACT

Erysipelothrix rhusiopathiae is a zoonotic, gram‐positive bacillus that is a virulent cause of infective endocarditis (IE) and incurs a high mortality rate. Its virulence is compounded by intrinsic resistance to common empirical agents including vancomycin and aminoglycosides. Given it is historically associated with a high rate of bacteraemia, its presentation in this case report as blood culture‐negative but tissue culture positive infective endocarditis is highly uncommon. We report the case of an immunocompetent female in her 60s with relevant environmental exposure presenting with acute heart failure. Later determined to be secondary to highly destructive, native IE confirmed on transesophageal echocardiography (TOE). Despite the significant burden of disease, three sets of blood cultures collected during a period without antibiotic treatment remained persistently negative. The patient underwent urgent mechanical aortic valve replacement. With the definitive diagnosis only being established post‐operatively after culture of the excised aortic valve tissue yielded E. rhusiopathiae . Following identification and susceptibility testing, antibiotic therapy was rationalized to 4 weeks of intravenous benzylpenicillin monotherapy, resulting in clinical recovery. This case highlights the rare but significant presentation of E. rhusiopathiae IE underscoring the critical role of advanced tissue diagnostics in high‐burden, culture‐negative endocarditis. Further, this case reinforces the need for clinicians to maintain a high index of suspicion for this organism in patients with relevant environmental exposures, ensuring timely initiation of appropriate antibiotic regimens particularly given its intrinsic resistance to commonly used empirical endocarditis therapies.

Key Clinical Message

Blood culture–negative infective endocarditis can be caused by Erysipelothrix rhusiopathiae , a zoonotic gram‐positive bacillus intrinsically resistant to vancomycin and aminoglycosides. In patients with relevant animal exposure and destructive valve disease, consider early valve‐tissue culture and/or 16S rRNA testing to enable prompt targeted therapy.

Echocardiographic evidence of Erysipelothrix rhusiopathiae infective endocarditis.

1. Introduction

Erysipelothrix rhusiopathiae is a globally distributed, pleomorphic, gram‐positive, non‐spore‐forming bacillus that is intrinsically resistant to glycopeptide antibiotics. It is generally regarded as a zoonotic pathogen [1]. Most human infections have been associated with occupational exposure to animals, particularly aquatic species and farm livestock [2]. Clinical manifestations in humans typically occur in three forms: localized cutaneous disease (erysipeloid), generalized cutaneous disease, and systemic infection often alongside bacteraemia, which is frequently complicated by IE [2]. Although musculoskeletal, intra‐abdominal, and central nervous system involvement have been documented, these manifestations remain uncommon [3].

The significance of gram‐positive rods isolated from blood cultures may be dismissed, particularly as clinically significant pathogens in this group are relatively rare and may represent contaminant skin flora from collection especially when compared to gram‐negative rods [4]. However, the significance of possible E. rhusiopathiae growth on culture should not be underestimated when grown from sterile samples, as misidentification or under‐recognition may lead to undertreatment [1]. The organism possesses several virulence factors including neuraminidase, which induces vascular damage, a polysaccharide capsule that confers resistance to phagocytosis, and adherence proteins with endothelial affinity that facilitate biofilm formation [1].

Antimicrobial susceptibility in vitro studies indicate that penicillins, cephalosporins, and imipenem exhibit the greatest bactericidal activity against E. rhusiopathiae . Conversely, the organism demonstrates intrinsic resistance to vancomycin, teicoplanin, cotrimoxazole, aminoglycosides, and rifampicin. These agents are frequently included in empirical regimens for severe gram‐positive infections and IE, particularly in β‐lactam‐intolerant patients [1]. This resistance profile underscores the importance of accurate identification and targeted antimicrobial therapy.

Historically, E. rhusiopathiae bacteraemia has been strongly associated with endocarditis. A systematic review spanning 1912 to 1988 reported that 90% of E. rhusiopathiae septicaemia cases were complicated by IE in a cohort of 49 cases [5]. By comparison, IE complicates bacteraemia caused by 18.2% of Staphylococcus aureus cases, 11.5% of Enterococcus faecalis cases, and 5.7% of Streptococcal infections [1]. IE due to E. rhusiopathiae predominantly affects native aortic and mitral valves, with a notable male predominance and alcohol use disorder identified as a probable risk factor. Outcomes are frequently poor, with reported mortality rates approaching 33% [1].

More recent data reinforces these observations. A systematic review of any form of E. rhusiopathiae infection cases in humans reported between 2000 and 2020 identified 62 infections, of which 37.1% involved endocarditis. Among these, 60.9% required surgical intervention, including nine aortic valve replacements and five mitral valve replacements [2]. These findings highlight the clinical severity and therapeutic challenges posed by this uncommon yet clinically significant pathogen.

2. Literature Review

A comprehensive literature search, completed for the purpose of this case report, of peer‐reviewed journals indexed in MEDLINE Complete, CINAHL Complete, and ScienceDirect from 1971 to 2025. With search terms ‘ Erysipelothrix rhusiopathiae ’ AND ‘Endocarditis’, 61 relevant articles were identified. As shown in Table 1, 26 cases involving human infections with evidence of E. rhusiopathiae IE were included.

TABLE 1.

Cases involving human infections with microbiological, radiological or intraoperative evidence of E. rhusiopathiae IE.

Case	Author, year	Means of diagnosis	Valve involvement	References
1	Veras, 2025	Blood culture positive	Mitral	[6]
2	Basu, 2013	Not specified	Mitral	[7]
3	Joo, 2011	Blood culture positive	Mitral	[8]
4	Barkhordarian, 2024	Blood culture positive	Aortic	[9]
5	Wojciech Jan Skorupski, 2021	Blood culture positive	Aortic	[10]
6	Wilson, 2019	Blood culture positive	Not specified	[11]
7	Sherlock, 2025	Blood culture positive	Aortic, Mitral	[12]
8	De Narvaez, 2022	Blood culture positive	Aortic, Mitral, Tricuspid	[13]
9	Boo, 2003	Tissue culture positive, Blood culture negative	Aortic	[14]
10	Urzedo, 2025	Blood culture positive	Mitral	[15]
11	Artz, 2001	Blood culture positive, Tissue culture negative	Aortic, Paravalvular abscess	[16]
12	Hill, 1997	Blood culture positive	Aortic, Tricuspid	[17]
13	Altibi, 2019	Blood culture positive	Aortic	[18]
14	Wang, 2020	Blood culture positive	Aortic	[19]
15	Sang‐Bae, 2003	Blood culture positive	Aortic	[20]
16	Yamamoto, 2008	Blood culture positive, 16S rRNA PCR result not specified	Tricuspid	[21]
17	Karambelkar, 2020	Blood culture positive	Tricuspid	[22]
18	Carson, 2005	Blood culture positive, histologically proven	Aortic, Mitral, Tricuspid	[23]
19	Balkhair, 2019	Blood culture negative, 16 s rRNA PCR positive	Mitral	[24]
20	Nielsen, 2018	Blood culture positive, 16S rRNA PCR positive	Aortic	[25]
21	Romney, 2001	Blood culture positive	Mitral	[26]
22	Campbell, 2013	Blood culture positive	Aortic	[27]
23	Tan, 2017	Blood culture positive	Aortic, Mitral	[28]
24	Chong, 1986	Blood culture positive	Not specified	[29]
25	Challa, 2023	Blood culture positive	Tricuspid	[30]
26	Rocha, 1989	Blood culture positive	Aortic	[31]

Only three cases were not reported to be blood culture positive; one case was blood culture negative but 16S rRNA PCR positive, one case was blood culture negative but tissue culture positive, and one case did not specify the means of diagnosis.

Valvular involvement, shown in Figure 1, was not specified in two cases. Among remaining cases, the aortic valve was involved in 62.5% of cases, mitral valve in 41.7%, and tricuspid in 25.0%. Multivalvular involvement was reported in five cases; three involved 2 valves, and two cases described involvement of 3 valves. One case reported a paravalvular abscess.

FIGURE 1.

Valvular involvement of literature search identified cases.

This literature review highlights the unique nature of case detailed below as well as the diagnostic challenges posed by atypical presentations, and the need for heightened clinical suspicion of E. rhusiopathiae when gram‐positive rods are isolated on appropriately collected blood cultures.

3. Case Presentation

An immunocompetent female in her 60s from a rural setting, with a medical history only notable for prior episodes of lower limb cellulitis and significant alcohol use, presented with a seven‐day history of progressively worsening exertional dyspnoea, orthopnoea, and paroxysmal nocturnal dyspnoea. She reported her symptoms had escalated significantly in the 48 h preceding admission accompanied by non‐specific chest pain. The patient reported an antecedent, non‐system specific febrile illness several months prior.

She had recently ceased both smoking (fifteen pack‐year history) and alcohol (approximately ten standard drinks per day) 1 month prior to presentation. She denied any history of intravenous drug use. Environmental history revealed proximity to livestock (neighboring cattle, chickens, and deer) and the presence of domestic animals (a dog), though she denied any mucosal/bodily fluid exposure or associated injury.

Upon presentation to her local hospital, she was afebrile and initial examination revealed normal vital signs. Cardiopulmonary auscultation uncovered diminished breath sounds with bi‐basal crackles and a soft diastolic murmur. She had mild bilateral pedal oedema confined to the ankles; however, her jugular venous pressure was normal on examination. Her dental hygiene was unremarkable and there were no peripheral stigmata of IE or embolic phenomena.

4. Investigations and Diagnosis

Initial laboratory evaluation demonstrated evidence of acute inflammation and myocardial strain: white blood cell count was 13.3 × 10⁹ cells/L, C‐Reactive Protein was 87 mg/L, and high‐sensitivity Troponin I was initially mildly elevated at 163 ng/L and static on repeat testing. B‐type Natriuretic Peptide was significantly elevated at 2510 pg/mL. An acute renal injury was noted with an acutely decreased eGFR of 41 mL/min/1.73 m².

A computerized‐tomography (CT) pulmonary angiogram excluded pulmonary embolism but confirmed features of severe biventricular failure, including large bilateral pleural effusions and a small pericardial effusion. Further investigations identified rhinovirus on respiratory swab and Enterococcus faecium on urine culture (ampicillin‐resistant, vancomycin‐sensitive) which was deemed in keeping with a contaminant, particularly given the absence of any dysuria/pyuria.

A transthoracic echocardiogram (TTE), shown in Figures 2, 3, 4, performed on day three of admission identified a mobile echodensity attached to the aortic valve associated with moderate aortic regurgitation, raising suspicion for IE.

FIGURE 2.

Pre‐operative TTE demonstrating an independently mobile lesion attached to the aortic valve measuring ~0.68 cm, at least moderate aortic regurgitation, mild–moderate mitral regurgitation.

FIGURE 3.

Pre‐operative TTE demonstrating an independently mobile lesion attached to the aortic valve measuring ~0.68 cm, at least moderate aortic regurgitation, mild–moderate mitral regurgitation.

FIGURE 4.

Pre‐operative TTE demonstrating an independently mobile lesion attached to the aortic valve measuring ~0.68 cm, at least moderate aortic regurgitation, mild–moderate mitral regurgitation.

Empiric intravenous 2 g ceftriaxone and 500 mg azithromycin were initiated by the treating team at admission. This was subsequently discontinued after 3 days due to an absence of any microbial evidence on blood cultures taken during the first 3 days of admission as well as the absence of any clinical syndrome strongly suggestive of endocarditis following the local infectious diseases (ID) team review.

A CT angiogram of the chest subsequently excluded aortic dissection as a cause of her aortic regurgitation.

Transoesophageal echocardiogram (TOE) on day five was reported as showing bivalvular native infective endocarditis with a heavy burden of vegetations on both the aortic and mitral valves. The TOE, shown in Figures 5, 6, 7, 8, 9, visualized a highly mobile, filamentous vegetation (1.4 × 1.29 cm) in the left ventricular outflow tract with severe aortic regurgitation, significant mitral regurgitation and a mitral leaflet perforation with two regurgitant jets. No root abscess was identified.

FIGURE 5.

Pre‐operative TOE demonstrating a highly mobile, filamentous vegetation (1.4 × 1.29 cm) in the left ventricular outflow tract with severe aortic regurgitation, significant mitral regurgitation, and a mitral leaflet perforation with dual jets.

FIGURE 6.

Pre‐operative TOE demonstrating a highly mobile, filamentous vegetation (1.4 × 1.29 cm) in the left ventricular outflow tract with severe aortic regurgitation, significant mitral regurgitation, and a mitral leaflet perforation with dual jets.

FIGURE 7.

Pre‐operative TOE demonstrating a highly mobile, filamentous vegetation (1.4 × 1.29 cm) in the left ventricular outflow tract with severe aortic regurgitation, significant mitral regurgitation, and a mitral leaflet perforation with dual jets.

FIGURE 8.

Pre‐operative TOE demonstrating a highly mobile, filamentous vegetation (1.4 × 1.29 cm) in the left ventricular outflow tract with severe aortic regurgitation, significant mitral regurgitation, and a mitral leaflet perforation with dual jets.

FIGURE 9.

Pre‐operative TOE demonstrating a highly mobile, filamentous vegetation (1.4 × 1.29 cm) in the left ventricular outflow tract with severe aortic regurgitation, significant mitral regurgitation and a mitral leaflet perforation with dual jets.

The patient was immediately re‐commenced on empirical antibiotics for blood culture‐negative IE with intravenous 2 g once daily ceftriaxone, 2 g six hourly flucloxacillin, and a single dose of 7 mg/kg intravenous gentamicin for coverage of ‘some form of virulent organism’, presumed to be of an oral source at the time. The three sets of blood cultures collected after initial ID review during a period without antibiotics (days three, four and five of admission) remained negative despite seemingly worsening infective endocarditis.

5. Management and Outcome

Given the severity of the valvular damage, the high burden of vegetation, and the embolic risk, the patient was urgently transferred to a tertiary centre where she underwent an urgent mechanical aortic valve replacement. Intraoperatively there were 2 large vegetations in the right coronary cusp and one small vegetation in the non‐coronary cusp; interestingly, there was no evidence of any mitral vegetations. Post‐operative TTE confirmed the mechanical aortic valve prosthesis function and, notably, demonstrated no residual mitral valve pathology.

Pre‐ and post‐operative blood cultures remained persistently negative. Extended serological work‐up for other causes of blood culture‐negative endocarditis including ANA, p‐ANCA, c‐ANCA, Anti‐GBM, MPO, PR3, and Q fever serology was unrevealing.

Day six post operatively, the histological tissue cultures grew an alpha‐haemolytic pathogen. With this development, the ID team commenced vancomycin and ceased flucloxacillin. The definitive diagnosis was achieved on day eight post‐operatively when intraoperative aortic valve tissue culture yielded growth of E. rhusiopathiae . Antibiotic therapy was subsequently rationalized to IV Benzylpenicillin monotherapy 2.4 g four hourly for a total planned duration of 4 weeks, reflecting the organism's known susceptibility to Penicillin G (MIC 0.016) and Ceftriaxone MIC (0.064).

The patient's recovery during the remainder of this admission was uncomplicated. She was afebrile and transferred to her local hospital for ongoing care and discharge planning.

Four weeks post‐discharge, she developed an uncomplicated peripherally inserted central catheter line infection. This was managed empirically with a course of intravenous antibiotics. Serial blood cultures at this stage were negative, with only one bottle growing coagulase‐negative Staphylococcus sp. after a prolonged incubation (24.3 h) consistent with skin contamination. The patient remained clinically stable, afebrile, with down trending C‐reactive protein, and no echocardiographic evidence of recurrent IE on TTE or TOE.

The eight‐week post‐aortic valve replacement review was entirely uncomplicated, and the patient was clinically well.

6. Discussion

This case represents an instance of blood culture‐negative but histologically proven E. rhusiopathiae native aortic valve infective endocarditis. While E. rhusiopathiae accounts for a small fraction of IE cases, it is disproportionately associated with poorer outcomes.

Typically, E. rhusiopathiae endocarditis exhibits a high association with bacteraemia compared to other common IE pathogens. The presentation of this case as blood culture‐negative endocarditis, despite the high burden of disease, runs contrary to the established trend; this may be contributed by potential low‐grade/intermittent bacteraemia, potential fastidious growth or the initial incomplete treatment with ceftriaxone.

The apparent discrepancy between TOE and surgical findings may be explained by imaging artifact or interpretation differences, particularly in the context of severe aortic valve destruction and turbulent regurgitant flow. It is also possible that the mitral abnormality represented a transient lesion or secondary functional mitral regurgitation rather than persistent structural mitral valve infection.

This patient's clinical course underscores the diagnostic challenge posed by blood culture‐negative IE. In such settings, particularly those with highly destructive lesions demanding urgent surgery, advanced microbiological techniques are essential. Molecular diagnostics, such as 16S rRNA PCR, offer a powerful tool for pathogen identification in valve tissue when culture results are inconclusive or delayed. Although the diagnosis was eventually confirmed by traditional tissue culture in this case and fortunately the patient made a clinical recovery, a molecular approach may have expedited pathogen identification.

E. rhusiopathiae is linked to a relatively high mortality rate, which is attributed not only to its high virulence—as evidenced by the severe aortic and mitral regurgitation and valvular perforation noted on TOE in this patient—but also potentially to delays in initiating appropriate antibiotic therapy. Likely due to its propensity to being dismissed as a gram‐positive contaminant as well as its intrinsic resistance to vancomycin and aminoglycosides, which are often part of the empirical therapy for IE.

Clinicians should maintain an index of suspicion for this organism. E. rhusiopathiae should be considered in the differential diagnosis of IE, especially in patients with any history of occupational or environmental animal exposure. This case highlights the importance of closely monitoring the clinical course of all patients with suspected IE after the initiation of empirical antibiotics, as well as having a low threshold to rationalize antimicrobial therapy to include agents effective against this pathogen such as benzylpenicillin or ceftriaxone, if there is clinical worsening or plateau of improvement.

Author Contributions

Mahdid Azam: conceptualization, data curation, investigation, methodology, project administration, writing – original draft, writing – review and editing. Abbey Isaac: conceptualization, data curation, methodology, project administration, writing – original draft, writing – review and editing. Hashim Azam: conceptualization, data curation, project administration, writing – original draft. Raja Chinthamuneedi: data curation, resources, writing – original draft, writing – review and editing. Robert Horvath: conceptualization, supervision, writing – review and editing.

Funding

This work was supported by the University of Queensland.

Consent

Written informed consent was obtained from the patient for publication of this case report.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.