Urothelial Carcinoma Associated with Infective Endocarditis Due to a Leuconostoc Species: A Rare Presentation

Table of contents

1. Introduction

nfective endocarditis (IE) is commonly caused by the hematogenous spread of various microorganisms that target the endocardium with staphylococci and streptococci accounting for the majority of cases. Due to the multitude of bacterial and even fungal pathogens, treatment options should be targeted specifically against microorganisms that are isolated in blood cultures. If an empiric antibiotic therapy is warranted, first-line treatment usually targets methicillin susceptible and resistant staphylococci, streptococci, and enterococci. Although there is an important caveat, clinicians must consider when using vancomycin antibiotic therapy.

Leuconostoc is a genus of gram-positive bacteria, placed within the family of Lacto-bacillaceae, this type of bacteria, which can be found in green vegetables and are used in wine, cheese, and sugar production, is an uncommon cause of disease in human beings(1); these microorganisms have only recently been recognized as a potential cause of infection in a variety of patient populations(2) II.

2. Case Report

We report the case of a 60 years old male, with a medical history ofnasopharyngeal carcinoma 26 years ago treated by chemotherapy and radiotherapy complicated with hypothyroidism under levothyroxine, our patient was diagnosed with a right renal urothelial carcinoma (UC) 2 years ago that was treated with surgery, an end stage kidney failure undergoing dialysis twice a week using a tunneled central venous catheter that was placed 3 years ago and a deafness caused by an operated cholesteatoma.

Author ?: e-mail: [email protected]

The patient was admitted in the cardiology department for significant weight loss associated to nausea, vomiting, dyspnea, total hematuria and episodic fever (39°C) for the last 2 months. The medical examination revealed a conscious patient with a blood pressure of 100/64 mmHg, heart rate of 113bpm, temperature of 38.5 C, respiratory rate of 18cpm, and oxygen saturation of 97% on room air. The cardiovascular examination found a grade IV/VI systolic and diastolic murmurs, no Janeway lesions or Osler nodes were found.

Complete blound count found an anemia with a hemoglobin rate at 5g/dl, white blood cell count (WBC) at 18,000/ ml, C-reactive protein (CRP) elevated at 104 mg/dl, Procalcitoninat1, erythrocyte sedimentation rate (ESR) was 48 mm, creatinine (Cr) 40.6 mg/dl, with a GFR of 15 ml / min / m²; a positive rheumatoid factor, hypothyroidism with a pituitary thyroid stimulating hormone at 100mUI/l.

The EKG showed an incomplete left bundle branch block with noanginal symptoms, transthoracic echocardiography (TTE) showed a mitral valve with calcified leaflets, moderate mitral regurgitation (Fig. 1), severe mitral stenosis with a valve area of 1.5cm2, and a mobile vegetation measuring 14x6 mm on A2 part of the anterior mitral valve (Fig 2 and 3). We also observed a tricuspid aortic valve with calcified leaflets and reduced cusp separation, moderate aortic regurgitation, moderate aortic stenosis with a valve area of 1.2 cm2. The left ventricular size was within normal limits and the left ventricular ejection fraction was 63%. Transoesophageal echocardiography (TEE) showed a 16x8 mm mitral vegetation .An empirical antibiotic therapy was initiated after the collection of recipient blood samples for culturing.

Leuconostoc species grew in 2 out of 2 blood cultures. Antibiotic treatment was adapted to the antibiogram with ceftriaxone and gentamicin. A cranial and Thoracoabdomino pelvic scan were realized and revealed an occipital ischemic injury, bilateral mild pleural effusion, metastatic damage to the liver, bladder tumor occupying all the lumen measuring 59x56x49mm and a mild peritoneal effusion.

Considering the results of imaging studies, clinical findings and blood tests, a diagnosis of infective endocarditis due to leuconostocspp was established. When dealing with IE caused by Leuconostoc, vancomycin is not a suitable option for treatment. Leuconostoc is catalase-negative, produces lactic acid, and is characterized by its intrinsic and chromosomal resistance to vancomycin. (2,3,4). It was previously believed that this bacterial species was non-pathologic in nature until recently published reports revealed the infectious potential of the Leuconostocspecies in many patient populations (5,6).

The patient received intravenous antibiotic therapy consisting of ceftriaxone 2g and gentamycin adapted to renal function.

The Nephrologyteam was consulted to assist in the management of the patient's chronic kidney disease. Throughout the patient's hospitalization, his tunneled central venous catheter was removed and the patient received a transfusion of 4 blood bags perdialysis because of his severe anemia with a control of hemoglobin at 9.5g/dl.

During his hospitalization, the patient had a transurethral endoscopic bladder resection of his mass that revealed a secondary extension of his primary renal cancer.

Otherdepartments took part in the management of our patient, endocrinology with the adaptation of doses of L-thyroxin and Oncology team who pronounced that his cancer is in a late stage and decided for a palliative chemotherapy after treatment of his actual endocarditis.

2 months after his discharge from cardiology department, a palliative chemotherapy was decided by oncologists but the patient died from a severe hematuria before starting his chemotherapy.

3. III.

4. Discussion

This case reports a story of a cancer patient afflicted by a complicated course of infective endocarditis with an uncommon organism: leuconostocspp. What had initially been described as a nagging headache, quickly developed into what we now know to be Leuconostoc species bacteremia from seeded aortic valves. In evaluating what may have led to this patient's eventual clinical course, it is imperative to note all predisposing factors. Our patient had a history of nasopharyngeal cancer, a renal carcinoma and a chronic renal failure undergoing dialysis with a persistent central venous catheter that was never changed and kept over 3 years, all of those factors had placed our patient at an extremely elevated risk for infective endocarditis. This case is interesting because the pathogenic bacterial species for IE are typically staphylococci and streptococci, not Leuconostoc species. (1) Until 1985, Leuconostocs were known as ''nonpathogenic to plants and animals''. However, due to continued reports of different infections, they are currently recognized as opportunistic pathogens affecting patients with a wide spectrum of underlying diseases; Still the portal of entry remains uncertain. One possibility is their introduction into the blood stream during catheter implantation, which could explain the case of our patient, another portal of entry is the gastrointestinal tract due to the natural habitat of Leuconostoc in food, which would explain the association with underlying gastrointestinal disease and frequent gastrointestinal symptoms. (7) Leuconostoc is a genus of Gram-positive, catalase and oxidase negative, chain forming ovoid cocci placed within the family of leuconostocaceae (1,5,8). This bacterial species was thought to be nonpathologic until recently published reports have revealed theirinfectious potential in immunocompromised and severely ill patients. IE with Leuconostoc species can be troubling considering they are hetero-fermentative and potentially "slime" (dextran and sucrose producing) forming. (9,10).

High-level resistance to vancomycin is nearly a constant in Leuconostoc species. Reports suggest the involvement of a chromosomal factor, which leads to a change in the end of a pentapeptide in the cell wall. This vancomycin binding side usually ends in alaninealanine, but in Leuconostoc species it ends in alaninelactate. Another possibility, as in Enterococci, is the production of a new membrane protein codified by plasmids (11).

Concerning treatment, multiple studies showed that the complete elimination of most bacterial pathogens of endocarditis needs two to four weeks of monotherapy, so we opted to treat our patient for six weeks following the American Heart Association (AHA) guidelines for treatment of penicillin-resistant bacteria in a high-riskpatient (12,15). Additionally, the AHA advises that daptomycin alone is not effective against multidrug resistant IE and should be used in combination with other agents (12). Upon further review of the available literature on Leuconostoc species infection, several studies listed daptomycin as an effective treatment for Leuconostoc-associated bacteremia (13). Considering our patient had anuncommon bacteria and an aortic valve vegetation, we pursued a full six-week course of an intravenous antibiotic therapy. As published reports do show effective therapy of penicillin-resistant group viridians streptococci with combination therapy, typically ceftriaxone or penicillin with gentamycin (14,15), our team opted for empiric treatment with ceftriaxone associated to gentamycine.

5. IV.

6. Conclusion

Infective endocarditis can prove to be a threatening disease when left untreated also if caused by a new organism. It is critical for clinicians to be aware of the many pathogenic organisms, including Leuconostoc species, and appropriate management strategies in order to avoid different complications that may ensue. It is also clear that a higher index of suspicion must be maintained in patients with multiple predisposing factors such as the patient in the case presented.

Figure 1. I
Urothelial Carcinoma Associated with Infective Endocarditis Due to a Leuconostoc Species:A Rare Presentation
Figure 2. Figure 1 :Figure 2 :I
12Figure 1: Moderate mitral regurgitation
Figure 3. Figure 3 :I
3Figure 3: The mitral vegetation measuring 18*9mm

Appendix A

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Date: 2022-01-04