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Subcutaneous
port-related Candida endocarditis with impact on the right atrial septum –
First reported case and review of literature.

Abstract:

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The use of subcutaneous catheter devices has increased over
the past two decades along with its associated infections. One of the
complications are infective endocarditis (IE), which usually occurs on the
valves of the heart. However, IE can rarely occur on the atrial septal wall.
The most common pathogens associated with catheter-related IE are
staphylococcus bacteria, and it is rarely caused by fungi. We present a case of
a 77-year-old Caucasian female with infective endocarditis located on the right
side of the atrial septum, caused by Candida
albicans due to the use of a subcutaneous catheter port. We will discuss
the diagnostic criteria and treatment plan for this patient, and other
treatment options available for these cases. To our knowledge a similar case
was reported in Brazil, but this is the first reported case in the United
States of catheter-related infective endocarditis of the right atrial septal
wall due to Candida albicans.

Introduction:

Infective endocarditis is described as an infection of the
endothelial lining of the heart (1). Native or prosthetic valves are usually
involved, but it can also involve adjacent structures or cardiac devices (1). Right-sided
endocarditis is rare due to lower hemodynamic pressures, but the risk increases
significantly in patients using central venous catheters (2). The diagnosis of
IE can be easily established in patients with classic features like fever, new
cardiac murmur, or bacteremia (1). However, in clinical practice atypical
presentations occur frequently, which makes the diagnosis more difficult. Therefore,
the diagnosis of IE should depend on integrating multiple factors like
clinical, microbiological, imaging and laboratory findings (1). The treatment
for cases with no valvular involvement is still not completely understood (2).
We present a case of a 77-year-old Caucasian female with infective endocarditis
located on the right side of the atrial septum, caused by Candida albicans due to the use of a subcutaneous catheter port.

Case
Presentation:

History and physical
examination:

The patient is a pleasant 75-year-old Caucasian female, who
was feeling unwell a day before coming to the hospital. According to her family
she was febrile with a temperature 103 F. She could not provide much
information. Most of her information was obtained from past medical records. She
was doing well and was afebrile during initial presentation. She did not
mention any chest pain, pressure, or heaviness. She denied any nausea,
vomiting, or diarrhea, upper respiratory symptoms, sore throat, or ear aches.
Her past medical history consisted of the following: recurrent urinary tract
infection, multidrug resistant infections and colonization with extended
spectrum beta lactamase (ESBL) infection, previous Clostridium difficile
colitis infection, recent acute kidney injury, non-insulin dependent diabetes
mellitus, hypertension, encephalopathy, functional quadriplegia, history of an
old cerebrovascular accident (CVA) with deficit, chronic diastolic heart
failure, septic arthritis (treated years ago), anemia, coronary artery disease
(CAD), rheumatoid arthritis (RA) with deformity, osteomyelitis of the elbow,
and hyperlipidemia. Her past surgical history included a cholecystectomy,
surgery of both knees, bypass heart surgery, and cardiac catheterization. The
patient lived a very sedentary lifestyle and required assistance in activities
of daily living.  

On physical examination, the patient was in slight
distress. Her vitals were as follows: blood pressure of 103/64, pulse of 77
beats per minute, respiratory rate of 20 breaths per minute, and temperature of
103 F.

The patient had bilateral arcus senilis. The head was
atraumatic and normocephalic. Pupils were equal, round and reactive to light
and accommodation. There was no pallor or icterus. The ears were remarkable.
The throat was within normal limits. There was a carotid bruit on neck
examination. The neck was supple with no lymphadenopathy or thyromegaly. S1 and
S2 were normal but there was a systolic ejection murmur, unchanged from
previous exam at the right sternal border. Respiratory sounds were clear to
auscultation with no wheezes, crackles or bronchial breath sounds. The stomach was
distended but bowel sounds are audible. There was no visceromegaly. There were
chronic changes in both extremities but absence of Osler nodes or Janeway
lesions. Peripheral pulses were somewhat depressed. The patient had deformities
of rheumatoid arthritis, but no symptoms of acute inflammatory arthritis. The
patient had contractures of both lower and upper extremities. There was speech
impairment and diffuse muscle weakness. Deep tendon reflexes were depressed.
Cranial nerve testing was significant for right-sided facial asymmetry.

Hospital Course

Considering the fever and new heart murmur in this patient,
blood cultures, urine cultures, complete blood count, metabolic panel, and
urinalysis were ordered for the patient. Her blood cultures grew Candida in
both bottles. Subsequently, her subcutaneous port device was immediately
removed and a 2D echocardiogram was ordered. She was given intravenous fluconazole.
Give her family’s request and past medical history, surgical intervention was
not performed.

In addition to blood cultures being positive for Candida albicans, urine cultures were also
positive for gram-negative bacilli. The hematology results showed a
significantly high white blood cell count with neutrophil predominance, as
shown in table 1. The coagulation results are shown in table 2. The metabolic
panel is shown in table 3. The urinalysis results are shown in table 4. The 2D
Echocardiogram results showed vegetation on the right atrial septum, as labeled
in figure 1. In comparison, her previous 2D echocardiogram from few months ago
showed no vegetations, as shown in figure 2.

Considering a recent acute kidney injury in our patient, amphotericin B was avoided,
and patient was started on Caspofungin for the initial treatment, followed by
lifelong suppression with fluconazole.

Table
1: Hematology results

Collected

Result

Units

Reference
range

White
blood cells

14.7

X10^3

4.8-10.8

Hemoglobin

11.8

X10^6

12.0-16.0

Mean
corpuscular hemoglobin concentration

31.8

g/dl

33.0-37.0

Red
cell distribution width

17.2

%

11.5-14.5

Neutrophils

89.4

%

42.0-75.0

Lymphocytes

0.9

%

20.0-40.0

Monocytes

9.2

%

2.0-7.0

Neutrophils

13.1

X10^3

1.5-7.1

Lymphocytes

0.1

X10^3

0.7-4.3

Monocytes

1.3

X10^3

0.2-1.2

 

Table
2: Coagulation results

Collected

Result

Units

Reference Range

Prothrombin
time (PT)

14.7

Seconds

9.3-11.9

International
normalized ratio (INR)

1.42

 

0.87-1.13

Partial
thromboplastin time (PTT)

38.6

Seconds

23.8-33.3

 

Table
3: Metabolic Panel

Collected

Result

Units

Reference Range

Sodium

145

mEq/dl

136-145

Potassium

3.4

mEq/dl

3.5-5.1

Chloride

113

mEq/dl

98-107

Calcium

8.0

mg/dl

8.5-10.1

Albumin

2.7

g/dl

3.4-5.0

Lactate

1.6

mmol/l

0.4-2.0

Glucose

181

mg/dl

70-99

Blood
urea nitrogen

23

mg/dl

7-18

Creatinine

1.37

mg/dl

0.55-1.02

Albumin

3.3

g/dl

3.4-5.0

Aspartate
aminotransferase

11

U/L

15-37

Alanine
aminotransferase

14

U/L

14-59

Sedimentation
rate

30

mm/hour

0-20

Procalcitonin

6.96

ng/ml

0-1.90

C-reactive
protein

2.1

mg/dl

0.0-0.2

 

Table
4: Urinalysis result

Collected

Result

Units

Reference range

Appearance

Cloudy

 

clear

Color

Amber

 

Yellow,
straw, colorless, pale yellow

Specific
gravity

1.023

 

1.016-1.022

PH

5

 

5.0-7.0

Protein

+1

 

Negative

Bilirubin

+1

 

Negative

Blood

+1

 

Negative

Leukocytes

+1

 

Negative

Urine
blood glucose

2.0

mg/dl

Normal,
1

White
blood cells

21-50

 

0-2,
none seen

Red
blood cells

11-20

 

0-2,
none seen

Bacteria

1+

 

None
seen

Mucus

3+

 

None
seen

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure
1: 2D echocardiogram results

2D echocardiogram of the patient, showing an infective vegetation
(red circle) attached to the right side of the inter-atrial septum. RA=right
atrium, LA=Left atrium

 

 

 

 

Figure
2: Previous 2D echocardiogram results

2-D echo-cardiogram result of the patient from January 2016,
showing a normal interatrial septum (red circle) with no vegetations. RA = right
atrium, LA = left atrium, RV = right ventricle, LV = left ventricle

 

Discussion:

The clinical manifestations of IE can range from acute and
rapidly progressing to chronic with non-specific symptoms (3). Fever is present
in up to 90% of patients and is the most common symptom (3). Patients may also experience
weight loss and chills (3). According to an article by Habib, et al. physicians
should suspect IE in patients with a new regurgitant murmur or embolic events
of unknown origin, or if there is sepsis of an unknown origin; especially if
the organism is known to be associated with IE. IE should be suspected if fever
is associated with the following: Cardiac prosthetic devices such as
implantable defibrillators or a prosthetic valve, previous history of IE,
previous valvular disease or congestive heart failure, immunosuppression,
intravenous drug abuse, recent treatment for associated bacteremia, blood
cultures positive for IE associated organisms or for chronic Q fever (Coxiella burnetii). Other signs of IE
associated with fever are vascular or immunologic phenomena, such as emboli,
Roth spots, Osler’s nodes, splinter hemorrhages or Janeway lesions. Peripheral
abscesses such as renal, splenic, cerebral, or vertebral lesions or a history
of a pulmonary embolism should also raise suspicion of IE. Physicians should
keep in mind that fever might not be present in patients that are elderly, immuno-compromised,
or were pre-treated with antibiotics (3).

About twenty percent of patients with IE also have cardiac
devices or prosthetic valves (4). The use of the modified duke criteria is not
as sensitive in this population group (4). The use of an echocardiogram is not
as accurate in these patients because the findings can be interpreted as
complex and inconclusive (4). Positron-emission computed tomography (PET/CT) can
be a useful addition for detecting IE in these patients (4). Pizzi, et al. performed
a cohort study on the effectiveness of using PET/CT in patients who were
diagnosed with suspected IE, specifically in patients with cardiac devices or
prosthetic valves. Ninety-two patients with suspected prosthetic valve or
cardiac device related IE from November 2012 to November 2014 were included. All
were given an echocardiogram and a PET/CT, and their findings were compared. They
found that adding PET/CT in addition to the duke criteria upon admission
increased the sensitivity of IE from fifty two percent to ninety one percent. The
diagnosis of possible IE cases upon admission were significantly reduced from
fifty four percent to five percent of patients. Diagnosing patients with
possible IE is a major issue in clinical practice because it can delay the
management process and cause complications. By reclassifying possible IE
patients into either definite or rejected IE, PET/CT could play a major role on
the management and prognosis of this patient population (4).

Prompt diagnosis and treatment of invasive Candida infection is essential for an
improved prognosis. However, early diagnosis is challenging. There is a candida
scoring system, which could help physicians identify patients that could
benefit from early antifungal treatment. The bedside candida scoring system
equation is calculated as follows: (0.908 x total parenteral nutrition) +
(0.007 x surgery) + (1.112 x multifocal Candida species colonization) + (2.038
x severe sepsis) (5). The variables are given the value one or zero depending
on whether they are present or not, respectively (5). A study by Leroy, et al.
evaluated the effectiveness of this score in a cohort study of critically ill
patients with candida infection. The cohort was performed from January 2010 to
March 2011 in five intensive care units (ICUs) in France. They included ninety-four
patients who developed hospital-acquired sepsis on ICU admission or during
their stay in the ICU. The incidence of invasive candidiasis was collected and
the relationship with the candida score was evaluated. They found invasive
candidiasis in five of the patients. They determined the rate of invasive
candidiasis was 0% in patients with a score of 2-3, 17.6% in patients with a
score of 4, and 50% in patients with a score of 5 (p<0.0001) (5). Even though this study was taken in the context of ICU patients with hospital-acquired sepsis, it could still be used by physicians to screen for Candida infection before waiting for blood culture results.  The treatment for cases of infective endocarditis from candida usually involves surgical removal of the infected valve, followed by an antifungal agent (6). The antifungals used are amphotericin B or its liposomal form, with or without adding flucytosine (6,7). Amphotericin B therapy is an effective non-surgical approach for patients with Candida infective endocarditis (7). Monotherapy with echinocandin (such as caspofungin and micafungin) can also be used as an initial treatment, especially for patients who are at increased risk of side effects from amphotericin B (8). The patients who can't undergo surgical procedure are recommended to receive lifelong suppression with oral fluconazole, after the initial therapy with amphotericin B or caspofungin. Surgery is recommended in patients with prosthetic related infective endocarditis (9). This patient's lesion was located on the wall of the atrial septum and she is elderly with multiple comorbidities; which made surgical intervention difficult. Physicians should always take into consideration factors such as age and past medical history before considering surgical intervention for infective endocarditis. Our review of the literature revealed one similar case reported in Brazil by De Araújo, et al. Their patient was a 49-year-old male on chronic dialysis with a tunneled catheter who presented with fever and chills. He also complained of dyspnea, dry cough and nausea. The patient had a venous catheter in the right subclavian vein. Cardiovascular examination showed no abnormalities. No other relevant information was found on physical examination. The blood cultures were positive for Candida parapsilosis. Transesophageal echocardiogram showed a mobile mass adhered to the inter-atrial septum close to the tip of the catheter. Their cardiology team decided not to perform surgery and initiated antibiotic therapy with Amphotericin B instead. They then switched the patient to Fluconazole. After three months of therapy, the patient was asymptomatic and showed no vegetation on transesophageal echocardiogram. Subsequently, antifungal treatment was suspended (2). This case showed similarities in terms of diagnosis and management, except we did not use Amphotericin B given our patient's circumstances. Conclusion: This was the first reported case of prosthetic-related endocarditis due to Candida albicans impacting the right atrial septal wall in the United States. This patient did not present with the typical features of IE. However, she was using a subcutaneous port device, which led to the suspicion of a possible IE induced by the device. This demonstrates the significance of taking a detailed patient history before ordering tests or forming differential diagnosis. It is important for physicians to suspect IE in febrile patients who use subcutaneous port devices, and promptly order a blood culture. If blood cultures are positive, removing the port device is highly recommended. Obtaining a transesophageal echocardiogram is also recommended. For patients requiring subcutaneous port devices, it is important that caregivers place the catheter tip correctly in the superior vena and confirm its location with imaging to avoid these complications. The transesophageal echocardiogram findings were critical in locating the vegetation in this patient. Physicians should avoid surgery in elderly patients with multiple comorbid conditions because it could lead to serious complications, such as bleeding. Non-surgical interventions with antifungal treatment have been proven effective in patients with candida associated infective endocarditis. The goal of presenting this case was to show that IE could occur in patients without valvular involvement. Hopefully there could be specific recommendations in the future on how to manage IE in patients without valvular involvement. References: 1.      Topan A, Carstina D, Slavcovici A, Rancea R, Capalneanu R, Lupse M. Assesment of the Duke criteria for the diagnosis of infective endocarditis after twenty-years. An analysis of 241 cases. Clujul Medical. 2015;88:321-326. doi:10.15386/cjmed-469. 2.    De Araújo GN, Valle FH, Freitas DM, Lampa FM, Gus M, Rohde LE. "Case Report: Catheter-related interatrial septum endocarditis caused by candida parapsilosis." International Journal of Cardiovascular Sciences. 2017;30:274-276 3.    Habib G, Hoen B, Tomos P, et al.: Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the task force on the prevention, diagnosis, and treatment of infective endocarditis of the European Society of Cardiology (ESC). Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC) for Infection and Cancer. Eur Heart J. 2009;30:2369-413. doi:10.1093/eurheartj/ehp285 4.    Pizzi MN, Roque Albert, Fernández-Hidalgo N, et al.: Improving the diagnosis of infective endocarditis in prosthetic valves and intracardiac devices with 18F-FDG-PET/CT-angiography: Initial results at an infective endocarditis referral center. Circulation. 2015;132:1113-26. doi: 10.1161/CIRCULATIONAHA.115.015316 5.    Leroy G, Lambiotte F, Thévenin D, Lemaire C, Parmentier E, Devos P, Leroy O. Evaluation of "Candida score" in critically ill patients: a prospective, multicenter, observational, cohort study. Ann of Intensive Care. 2011;1:50. doi:10.1186/2110-5820-1-50. 6.    Smego Jr, Raymond A., and Hassan Ahmad. "The role of fluconazole in the treatment of Candida endocarditis: a meta-analysis." Medicine 90.4 (2011): 237-249. 7.    Melamed R, Leibovitz E, Abramson O, Levitas A, Zucker N, Gorodisher R. Successful non-surgical treatment of Candida tropicalis endocarditis with liposomal amphotericin-B (AmBisome)." Scand J Infect Dis. 2000;32:86-9. doi: 10.1080/003655400458893 8.    Laniado-Laborín, R, Cabrales-Vargas MN. Amphotericin B: side effects and toxicity. Rev Iberoam Micol. 2009;26:223-7. doi: 10.1016/j.riam.2009.06.003. 9.    Kang DH. Timing of surgery in infective endocarditis. Heart. 2015;101:1786-1791.    

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