Case report

J. Bishara Infective endocarditis in renal transplant

E. Robenshtok
M. Weinberger recipients
M. Yeshurun
A. Sagie
S. Pitlik

Key words: Abstract: Because of the increasing number of renal transplantations Authors’ affiliations:
endocarditis; kidney; transplants performed and the rarity of reported cases of infective endocarditis in
J. Bishara1,
these patients, we studied the clinical characteristics of this infection in E. Robenshtok1,
M. Weinberger1,
this population. We report on two cases from our experience and review
M. Yeshurun2,
reported cases of infective endocarditis in renal transplant recipients re- A. Sagie3,
S. Pitlik1
trieved from the MEDLINE system. In addition, we reviewed a large series
of infective endocarditis looking for patients with renal transplants. In 1
Department of Internal
Medicine C, Rabin Medical
addition to our 2 cases, 12 previously reported cases were found. The
Center, Beilinson Campus,
mean time from transplantation to diagnosis of infective endocarditis Sackler School of Medicine,
Tel Aviv University, Petach
was 3.5 years (range 2 months to 15 years). Causative organisms included
Tikvah, Israel,
fungi, Staphylococcus aureus (3 cases each), Corynebacterium sp. (2
2
Department of Internal
cases), Streptococcus viridans, VRE, Brucella sp., Clostridium sp., Nocardia
Medicine E, Rabin Medical
sp. and Erysipelothrix sp. (one case each). Skin manifestations of endo- Center, Beilinson Campus,
Sackler School of Medicine,
carditis and/or splenomegaly were not reported in these patients. Septic
Tel Aviv University, Petach
emboli and mycotic aneurysms were relatively common. The overall mor- Tikvah, Israel,
tality rate was 50% (7 of 14 patients died). Infective endocarditis seems 3
Unit of Echocardiography
to be rare in renal transplant recipients. The few reported cases are char- and Valvular Heart Diseases,
Rabin Medical Center,
acterized by unusual causative micro-organisms and atypical clinical pres-
Beilinson Campus, Sackler
entation. Further studies are needed to delineate the magnitude and School of Medicine, Tel Aviv
University, Petach Tikvah,
scope of this association.
Israel

Correspondence to:
Dr. S. Pitlik
Department of Internal
Medicine C
Rabin Medical Center
Beilinson Campus
Petach Tikvah
Israel
Infective endocarditis remains a prevalent disease with a signifi- Tel: π972 3 9376301
Fax: π972 3 9221605
cant mortality in the antibiotic era (1, 2). Infective endocarditis is e-mail:
hshmuely/post.tau.ac.il
increasingly recognized as a nosocomial disease in many patients
(1). Nosocomial bacteremia occurs more frequently in immuno-
compromised patients, primarily after transplantation or multiple
invasive procedures (1). Although a proportion of these patients
Received 8 December 1998, revised,
accepted for publication 24 March 1999 develop endocarditis, this particular infection has been rarely re-
Copyright c Munksgaard 1999 ported in renal transplant recipients. We report herein two cases
Transplant Infectious Disease . ISSN 1398-2273
of infective endocarditis in patients with renal transplants, and
Transpl Infect Dis 1999: 1: 138–143
Printed in Denmark . All rights reserved review the pertinent literature.

138

Patients and methods
A literature review of endocarditis in renal transplant recipients was
performed via MEDLINE with the keywords endocarditis, trans-
plant, renal and kidney. Both English and non-English language
articles were retrieved. The review period included January 1970 to
July 1998. In addition, the references cited in the retrieved articles
were reviewed to detect additional cases. Only cases of endocarditis
that met the definition of definite infective endocarditis according
to the Duke criteria by Durack et al. (3) were included in the review.
Fig. 2. Transesophageal echocardiography demonstrating a 1.3
cm vegetation attached to the aortic valve (arrow).
Bishara et al : Infective endocarditis, renal transplant
Fig. 1. (A) CT scan of the brain showing an
intracerebral hemorrhage in the right frontal
lobe with signs of right lateral ventricle com-
pression. (B) CT scan of the brain showed in-
tracerebral bleeding in the left parietal lobe
(bold arrow).
Fourteen cases of infective endocarditis in renal transplant re-
cipients have been reported in the medical literature. Of these cases,
2 cases were excluded due to insufficient epidemiological and clin-
ical details (4).
The medical records of patients with clinical diagnosis of infec-
tive endocarditis who had been admitted to the Rabin Medical Cen-
ter, Beilinson Campus in Israel from January 1987 to December 1996
were reviewed (5). We also reviewed reports of large series of cases
(.100 cases) with infective endocarditis published from 1978 to
1998, looking for patients with underlying renal transplantation (2,
6–20).
Case 1
A 35-year-old female was admitted because of fever, vomiting, head-
ache and seizures. Five years earlier she had undergone renal trans-
plantation. Eight months prior to admission, chronic rejection was
diagnosed. Since then she had been managed with hemodialysis.
Her admission medication included azathioprine 75 mg/day and
prednisone 15 mg/day.
On admission laboratory studies revealed erythrocyte sedi-
mentation rate of 100 mm in the first hour, WBC 7900/mm3
(90% polymorphonuclear neutrophils); hemoglobin 7.6 g/dl; plate-
lets 62 000/mm3, serum creatinine 8.6 mg/dl; blood urea nitrogen
87 mg/dl; serum calcium 7.8 mg/dl, serum phosphorus 5.7 mg/
dl. Results of glucose, electrolytes and liver enzymes were nor-
Transplant Infectious Disease 1999: 1: 138–143 139
Bishara et al : Infective endocarditis, renal transplant
mal. Computed tomography (CT) of the brain revealed several
lesions compatible with acute intracerebral hemorrhages (Fig. 1).
Cerebral angiography was normal. Transesophageal echocardiog-
raphy demonstrated a 1.3 cm mobile lesion, attached to the aor-
tic valve, compatible with a vegetation (Fig. 2). Five consecutive
blood cultures grew Erysipelothrix rhusiopathiae. Speciation of
the micro-organism was confirmed at the Center for Disease
Control and Prevention, Atlanta, Georgia. On further questioning,
the patient recalled having cleaned her own aquarium several
weeks previously. Aquarium water cultures for Erysipelothrix
rhusiopathiae were negative. She was treated with intravenous
ceftriaxone, 1 g daily, for 6 weeks. Blood cultures taken 2 and
4 weeks after completion of therapy were sterile. The patient
recovered from her neurological deficits; follow-up echocardiogra-
phy revealed no aortic regurgitation and an excellent ejection
fraction of 55%. A repeated CT of the brain, one year later, was
interpreted as normal.
Case 2
A 41-year-old male sheep owner, 3 years after kidney transplantation,
was admitted with fever, weakness and a mild headache of 3 days’
duration. His maintenance immunosuppressive therapy included aza-
thioprine 150 mg/day and prednisone, 20 mg/day. On admission,
physical examination was unremarkable. Routine blood tests showed
erythrocyte sedimentation rate of 102 mm in the first hour; WBC
5200/mm3 (65% polymorphonuclear neutrophils), hemoglobin 12.5 g/
dl; platelets 130 000/mm3, serum creatinine 1.6 mg/dl, blood urea ni-
trogen 47 mg/dl. The results of serum glucose, electrolytes, calcium,
phosphorus and liver enzymes were within normal limits.
Six consecutive blood cultures taken during a 4-day period subse-
quently yielded Brucella melitensis. At this stage the patient admitted
to having occasionally consumed unpasteurized goat’s milk during
the past 3–4 years and had delivered lambs several weeks earlier.
Transesophageal echocardiography demonstrated a 3-mm, mobile
vegetation on a normal mitral valve. Three days after starting ther-
apy with doxycycline and rifampin, the patient’s temperature was
normal and he felt well. Blood cultures taken a week later were sterile.
Combination therapy with doxycycline 100 mg bid, rifampin 600
mg/day and trimethoprim–sulfamethoxazole 160/800 bid for 6 weeks
resulted in a complete recovery without residual heart disease.
Results
Review of the medical literature revealed 12 previously reported
cases of infective endocarditis in renal transplant recipients (21–28).
140 Transplant Infectious Disease 1999: 1: 138–143
These cases as well as our 2 cases are summarized in Table 1. The
mean age of these patients at presentation was 45.5 years (range
29–67 years). The male:female ratio was 1.3. The mean time from
renal transplantation to diagnosis of infective endocarditis was 3.5
years (range 2 months to 15 years). Nine patients were receiving
immunosuppressive therapy, which included corticosteroids, aza-
thioprine and cyclosporin A.
According to the Duke criteria (3) the diagnosis of infective endo-
carditis was definite in all reported cases, including ours. The pres-
ence of endocarditis was confirmed by autopsy in 2 cases (nos. 1
and 2) and at the time of surgery in 5 cases (nos. 3–7). Eight cases
(nos. 2–7, 13 and 14) had positive blood cultures with typical echo-
cardiographic findings. Seven patients had abnormal renal function
at presentation (nos. 1, 2, 4, 6, 7, 13 and 14). Among them there
were 5 patients with rejection (nos. 1, 2, 6, 7 and 13). The aortic and
mitral valves were equally involved in 5 cases each, followed by the
tricuspid valve in 2 cases (nos. 3 and 5). There were 2 cases of
mural endocarditis without any valve involvement (nos. 1 and 2)
and one case of right coronary sinus abscess (case 7).
Extracardiac complications included septic pulmonary emboli
and mycotic brain aneurysms in 4 cases each (nos. 1, 3, 8 and 13),
and bilateral septic emboli to the femoral arteries in 1 case (no. 2).
Skin manifestations of endocarditis and/or splenomegaly were not
reported in these patients.
The organisms responsible for endocarditis in these patients are
shown in Table 1. Endocarditis due to bacterial infection occurred
in 11 patients (78.5%). Fungal endocarditis was found in 3 cases
(21%), 2 of them due to Candida albicans (nos. 3 and 5) and one due
to Aspergillus sp. (no. 1). Staphylococcus aureus was the cause of
infective endocarditis in 3 cases (21%) (nos. 10–12). Two patients
had endocarditis due to Corynebacterium sp. (nos. 6 and 7) and one
patient due to Erysipelothrix sp. (no. 13).
Complete recovery from the infection was reported in 7 cases
(nos. 3–5, 7, 9, 13 and 14). Death occurred in 7 (50%) cases (nos. 1,
2, 6, 8 and 10–12).
Discussion
We have described two cases of endocarditis caused by relatively
unusual organisms in two renal transplant recipient patients. To
our knowledge endocarditis caused by Erysipelothrix rhusiopathiae
and Brucella melitensis in renal transplant recipients has not yet
been reported.
Infection with E. rhusiopathiae has been associated with a wide
variety of occupations. Those at greatest risk include fishermen,
 Bishara et al : Infective endocarditis, renal transplant

Infective endocarditis in renal transplant recipients

Age
(years)/ Time since
No Reference gender transplantation Immunosuppressive therapy Micro-organism Involved valve Treatment Outcome
1 21 29/F NS Corticosteroids; cytotoxic Aspergillus sp. None1 A D
drugs (US)
2 22 53/M 4.5 years Corticosteroids; azathioprine Clostridium ramosum None1 A D

3 23 31/F 19 months Corticosteroids; azathioprine Candida albicans Tricuspid A,S C

4 23 29/M 9.5 years Corticosteroids; azathioprine Streptococcus Aortic A,S C

viridans

5 24 31/F 18 months Prednisone; azathioprine Candida albicans Tricuspid A,S C

6 25 41/M 4 years None JK Corynebacterium Aortic & A,S D

para-aortic abscess
7 26 35/M 2 months Cyclosporine A; azathioprine; Corynebacterium Right coronary sinus A,S C
methylprednisolone abscess

8 27 62/M 6 months Methlyprednisolone; Nocardia asteroides Aortic A D

cyclosporine A

9 28 60/F 2 months NS VRE Mitral A C

10 28 58/M 18 months NS S. aureus Mitral A D

11 28 65/F 3 years NS S. aureus Mitral (prosthetic) A D

12 28 67/M 15 years NS S. aureus Aortic & mitral A D

13 PR (1) 35/F 5 years Prednisone; azathioprine Erysipelothrix Aortic A C

rhusiopathiae

14 PR (2) 41/M 3 years Prednisone; azathioprine Brucella melitensis Mitral A C

1
PR, present report; NS, not stated; US, unspecified; mural endocarditis; A, antibiotics; S, surgery; D, death; C, cure, VRE, vancomycin-resistant enterococcus

Table 1

fish handlers, butchers, slaughterhouse workers, veterinarians and
housewives. Infection is especially common among individuals who
handle fish. The organism is communicable from animals to
humans by direct cutaneous contact (29).
Brucellosis is a worldwide zoonotic infection affecting more than
500 000 persons yearly. Endocarditis is the most devastating compli-
cation of this disease and is encountered in ,2% of these patients
(30). Our second patient had two risk factors for the acquisition of
brucellosis, i.e. direct exposure to parturient sheep and consumption
of unpasteurized milk products.
Kidney transplantation has become an accepted therapy for
many patients with end-stage renal disease. The quality of life and
survival rates following renal transplantation have significantly im-
proved owing to advances in surgical techniques, immunosuppres-
sive therapy and medical management. However, allograft rejection
and infection remain major causes of morbidity and mortality fol-
lowing renal transplantation (31). The spectrum of infection in this
group of patients has been studied extensively during the last two
decades (31–37); however, endocarditis is not mentioned in any of
these previous reviews.
Paterson et al. (28) found a prevalence of infective endocarditis
of 1.7% in a cohort of liver transplant recipients. They quoted a
study which reported a prevalence of infective endocarditis of 6%
among heart transplant recipients. They found no data from which
prevalence of endocarditis can be calculated among kidney trans-
plant recipients (28).
Approximately 30% of patients with end-stage renal disease
may develop premature aortic and mitral valve calcification. In a
small proportion of them, the calcification is severe and produces
aortic or mitral stenosis. Premature aortic and mitral valve calcifi-
cation is also frequent in dialysis patients and appears to be related
to abnormal calcium and phosphate metabolism due to uncontrolled
secondary hyperparathyroidism (38, 39).
Among the wide variety of infections in renal transplant recipi-
ents, septicemia is not uncommon and causes high mortality. The
urinary tract is the most common source of septicemia, followed by
the lung, the operative wound site, the abdomen and numerous
other sources (4, 37).
McHenry et al. (4) found only 2 patients with fulminant staphylo-
coccal endocarditis among 36 renal transplant recipients with 47
episodes of septicemia (not included in this review owing to lack of
details), whereas we could not find any episodes of infective endo-

Transplant Infectious Disease 1999: 1: 138–143 141

Bishara et al : Infective endocarditis, renal transplant

carditis among 258 renal transplants in 233 patients in our 5-year
retrospective survey (37). Based on our experience among 252 pa-
tients with infective endocarditis in a recent 10-year retrospective
survey (5), we found only 2 cases of community-acquired infective
endocarditis in renal transplant recipients (present case reports).
In several large series of infective endocarditis, published in the
English language medical literature (2, 6–20), we could not find any
case with underlying renal transplantation among reported cases of
endocarditis.
Several risk factors, such as frequent hospitalization, surgical
and other invasive procedures, uremia, and extensive use of im-
munosuppressive therapy, make kidney transplant patients prone
to infections in general and bacteremia in particular. The few cases
of infective endocarditis in renal transplant recipients reported in
the literature may not reflect the true prevalence of the disease.
Infective endocarditis in renal transplant recipients can be caused
by a variety of unusual and rare pathogens, including fungi and
agents of zoonoses.
Infective endocarditis in patients undergoing renal transplan-
tation and receiving immunosuppressive therapy may be difficult
to diagnose. Fever may be lacking; if present, it may be mistaken
for acute rejection, drug reaction or other infectious diseases rather
than infective endocarditis. The classic manifestations of endocar-
ditis, such as new murmur, Osler nodes, Roth spots, splinter hemor-
rhages, petechiae and splenomegaly usually are not seen in these
patients.
The early diagnosis of endocarditis is essential in order to in-
itiate appropriate antibiotic treatment. In selected cases, surgery can
be undertaken and prevent significant subsequent morbidity and
mortality. A high index of suspicion is required to make the diag-
nosis. Large prospective studies are required to delineate the true
incidence of infective endocarditis among the growing population
of renal transplant patients.

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