Premature newborn with intracardiac fungus balls and endocarditis which is curable only with anti-fungal therapy: Case presentation

doi:10.4236/crcm.2013.25084

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Vol.2, No.5, 315-317 (2013) Case Reports in Clinical Medicine

http://dx.doi.org/10.4236/crcm.2013.25084

Premature newborn with intracardiac fungus balls

and endocarditis which is curable only with

anti-fungal therapy: Case presentation

Mecnun Cetin*, Serkan Ozen, Munevver Yildirimer, Murat Deveci, Senol Coskun,

Metehan Kizilkaya

Division of Pediatric Cardiology, Department of Pediatrics, Faculty of Medicine, Celal Bayar University, Manisa, Turkey;

*Corresponding Author: [email protected]

Received 22 November 2012; revised 26 December 2012; accepted 3 January 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Invasive fungal infections often caused by Can-

dida species are infections which have high

morbidity and mort ality rates in newborn infant s.

5% of the cases have also concomitant endo-

carditis and this causes mortality rates ov er 60% .

Thus it has vital importance to diagnose and

treat these patients with endocarditis in early

stages. Most preferred treatment option is a sur-

gical incision in addition to systemic anti-fungal

therapy. Here we presented an extremely low

birth weight, premature newborn with endocar-

ditis caused by Candida tropicalis and cured

solely by systemic anti-fungal treatment without

the need for surgical intervention.

Keywords: Invasive Fungal Infection; Endocarditis;

Candida tropicalis

1. INTRODUCTION

Frequency of invasive fungal infection in newborns is

increasing due to the reasons such as increasing number

of low/extremely low birth weight newborns that are

hospitalized in newborn intensive care units, increased

invasive interventions, need for parenteral nutrition, use

of broad-spectrum antibiotics and need for long term

mechanical ventilation [1]. The most common infectious

agent is C. albicans. These fungal infections develop

severe symptoms in extremely low birth weight new-

borns and have mortality rates of 30% - 60% [2]. Endo-

carditis develops in 5% of invasive Candida infections

and these cases have over 60% mortality rate. In this

article a case of extremely low birth weight newborn

with endocarditis caused by Candida tropicalis and cured

by only systemic anti-fungal therapy due to high risk of

mortality with surgical intervention, anticoagulant and

thrombolytic treatment is presented.

2. CASE

Female baby, who was born 980 gr. from 24-year-old

mother’s first pregnancy, with C-section at 28 weeks

because of umbilical cord prolapse, had APGAR scores

of 3 and 7 respectively at 1st and 5th minutes. After five

hours, with onset of respiratory distress, grunting, apnea

and presence of acidosis and hypoxia in her arterial

blood gas, patient was intubated and connected to me-

chanical ventilator. Umbilical catheter was inserted and

TPN solution and sefotaxim (100 mg/kg/day, two doses)

plus amikacin (18 mg/kg/dose, in every 35 hours) was

initiated. With the detection of reticulonodular pattern in

PA chest radiography patient was diagnosed as respira-

tory distress syndrome and administered surfactant.

Complete blood count and biochemical values of the

patient were normal. On third day, stage III hemorrhage

in left hemisphere was detected on transfontanel ultra-

sonography. On the fourth day, Patent Ductus Arteriosus

(PDA) was found by transthoracic echocardiogram (TTE)

that was performed upon detection of 2/6 grade systolic

murmurs during cardiovascular system examination. Pa-

tient received three doses of intravenous ibuprofen (first

dose of 10 mg/kg and subsequent two doses of 5 mg/kg)

with 24 hour intervals. In control echocardiogram per-

formed one week later it was observed that PDA was

closed. However at the interconnection of vena cava in-

ferior and left atrium a hyperechoic mass (fungus ball) of

11.3 mm × 5 mm (Figure 1) was spotted. Same day as

yeast cell proliferation in previously collected blood cul-

ture sample was detected, abdominal catheter was re-

moved and systemic liposomal amphotericin B therapy

M. Cetin et al. / Case Reports in Clinical Medicine 2 (201 3) 315-317

316

Figure 1. Appearance of the fungus ball at interconnection of

vena cava inferior and right atrium (IVC: Inferior vena cava;

HV: Hepatic vein; RA: Right atrium).

(6 mg/kg/day, one daily dose) was initiated. Later it was

realized that proliferated agent in the blood culture was

amphotericin B sensitive Candida tropicalis and same C.

tropicalis proliferation was observed in both second

blood culture and abdominal catheter culture. There was

no proliferation in urine culture. Lumber puncture and

eye examination was normal. Patient was intubated and

extubated sporadically 3 times with recurrent severe ap-

nea exacerbations during the follow-ups. Surgical exci-

sion was planned for patient’s fungus ball in the vena

cava inferior but patient’s extremely low birth weight,

unstable clin ical condition and high cardio-pulmoner by-

pass risk postponed the surgery and only liposomal am-

photericin B therapy was continued. We couldn’t use

anticoagulant and thrombolytic treatment due to presence

of intracranial hemorrhage. In periodically obtained echo-

cardiograms of patient during follow-ups, shrinkage of

fungal mass was observed. At the 50th day of the anti-

fungal treatment complete disappearance of the mass was

observed (Figure 2) and treatment continued in follow-

ing next 10 days. Patient was administered 60 days of

anti-fungal therapy at total. There were no significant

side effects related to anti-fungal therapy. After clinical

stabilization was achiev ed during follow-ups, pa tient was

discharged from hospital as 2100 gr.

3. DISCUSSION

Candida species can cause organ specific invasive in-

fections aside from non-lethal local mucocutaneous in-

fections. Most common infectious agents in invasive

fungal infections are Candida species [3]. Recently in-

creased number of nosocomial Candida infections among

populations are reported all around the world. In 1960-

70’s most of nosocomial candidasis cases were caused by

Figure 2. Disappearance of fungus ball (IVC: Inferior vena

cava; HV: Hepatic vein; RA: Right atrium).

C. albicans however recently a significant increase in

incidence of infections caused by non-albicans Candida

species (C. tropicalis, C. glabrata, C. parapsilosis, C

krusei, C. guiliermondii, C. lipolytica, and C. pelliculosa)

has been observed [4]. In our case C. tropicalis prolifera-

tion was observed in blood culture.

Risk factors for invasive candidiasis in neonatal period

includes low gestational week, early membrane rupture,

use of H-2 receptor blockers in intensive care units, in-

tubation and mechanical ventilation, the presence of cen-

tral venous catheter, use of broad-spectrum antibiotics,

lack of enteral nutrition and utilization of to tal parenteral

nutrition [5,6]. Five of these risk factors were present in

our patien t .

Systemic fungal infection is reported in very low birth

weight infants less than 1500 g, as the third most fre-

quent cause of late-onset sepsis and is associated with

high mortality [7]. Fungal endocarditis is an uncommon

complication of invasive candidial infection, but there is

a reported increase in the incidence of such infection over

the last 15 years [8,9]. Therefore, early recognition of

infection and therap y is imperativ e.

Invasive candidiasis must definitely be considered in

cases with extremely low birth weight premature new-

borns who have risk factors for candidiasis. Successful

treatment of patients with endocarditis requires early re-

cognition and aggressive treatment. The first and most

basic principle of treatment is elimination of the source

that is associated with increased risk for candidiasis and

the second step is initiating appropriate anti-fungal ther-

apy.

Management of fungal endocarditis in premature in-

fants is controversial. Use of prolonged anti-fungal ther-

apy in conjunction with surgical removal of thrombus is

M. Cetin et al. / Case Reports in Clinical Medicine 2 (201 3) 315-317

317

[2] Zaoutis, T.E., Heydon, K., Localio, R., Walsh, T.J. and

Feudtner, C. (2007) Outcomes attributable to neonatal can-

didiasis. Clinical Infectious Diseases, 44, 1187-1193.

doi:10.1086/513196

shown to be an effective approach to the treatment o f th is

complication [10]. Use of prolonged anti-fungal treat-

ment alone is reported in few critically ill infants with

fungal endocarditis [11]. In our case, due to high risk of

mortality for cardiopulmoner bypass, only 60 days lipo-

somal amphotericin B therapy was administered. Due to

intracranial hemorrhage risk n o anticoagu lant and throm-

bolytic therapy was used. We observed that intracardiac

vegetation shrunk on the 20th day of the treatment and

completely disappeared on the 50th day. There are few

cases, similar to our case, in literature which are treated

and cured by only anti-fungal therapy without the use of

anticoagulants and thrombolytics and surgical interven-

tion.

[3] Lamagni, T.L., Evans, B.G., Shigematsu, M., et al. (2001)

Emerging trends in the epidemiology of invasive mycoses

in England and Wales (1990-9). Epidemiology & Infec-

tion, 126, 397-414. doi:10.1017/S0950268801005507

[4] Trick, W. (2002) Secular trend of hospital-acquired can-

didemia among intensive care unit patients in the United

States during 1989-1999. Clinical İnfectious Diseases, 35,

627. doi:10.1086/342300

[5] Manzoni, P. (2006) Risk factors for progression to inva-

sive fungal infection in preterm neonates with fungal

colonization. Pediatrics, 11 8, 2359-2364.

doi:10.1542/peds.2006-1311

Another aspect that we would like to highlight is the

prophylactic anti-fungal therapy in high risk extremely

low birth weight group patients. Although this is a con-

troversial topic, application of fluconazole prophylaxis

for <1000 gr. newborns have grade A1 level of evidence

in Infectious Diseases Society of America’s (IDSA) Prac-

tice Guidelines and 3 mg/kg fluconazole should be ap-

plied parenterally and in two divided doses for at least 14

days starting from the first day of life [12]. Reason for us

not initiating prophylaxis was due to low frequency of

candidiasis cases in our center.

[6] Benjamin, D.K. (2006) Neonatal candidiasis among ex-

tremely low birth weight infants: Risk factors, mortality

rates, and neurodevelopmental outcomes at 18 to 22

months. Pediatrics, 117, 84-92.

doi:10.1542/peds.2004-2292

[7] Stoll, B.J., Hansen, N., Fanaroff, A.A., Wright, L.L.,

Carlo, W.A., Ehrenkranz, R.A., et al. (2002) Late onset

sepsis in very low birth weight neonates: The experience

of NICHD Neonatal Research Network. Pediatrics, 110,

285-291. doi:10.1542/peds.110.2.285

[8] Kossoff, E.H., Buescher, E.S. and Karlowicz, M.G. (1998)

Candidemia in Neonatal Intensive Care Unit: Trend dur-

ing fifteen years and clinical features of 111 cases. Pe-

diatric Infectious Disease Journal, 17, 504-508.

doi:10.1097/00006454-199806000-00014

We suggest that prophylactic anti-fungal therapy is

essential in cases with high risk factors for invasive can-

didiasis during neonatal period. Besides, serial echocar-

diographic evaluation of newborns with invasive candi-

diasis for possible cardiac involvement should definitely

be performed.

[9] Faix, R.G. (1984) Systemic candida infections in infants

in intensive care nurseries, high incidence of central ner-

vous system involvement. Journal of Pediatrics, 105,

616-622. doi:10.1016/S0022-3476(84)80433-3

As a result, solitary long-term systemic anti-fungal

treatment can be a favorable treatment option in newborn

patients with fungal endocarditis, such as the one in our

case, where surgical intervention, anticoagulant or throm-

bolytic therapy due to their high risk.

[10] Ankola, P.A., Perveen, S. and Fish, B. (2006) Fungal en-

docarditis. Journal of Perinatology, 26, 509-510.

doi:10.1038/sj.jp.7211557

[11] Zenker, P.N., Rosenberg, E.M., Van Dyke, R.B., Rabalais,

G.P. and Daum, R.S. (1991) Successful medical treatment

of presumed Candida endocarditis in critically ill infants.

Journal of Pediatrics, 11 9, 472-477.

doi:10.1016/S0022-3476(05)82067-0

REFERENCES

[1] Kaufman, D., Boy le, R., Hazen, K.C., Patrie, J. T., Robin-

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[12] Pappas, P.G. (2009) Clinical practice guidelines for the

management of candidiasis: 2009 update by the infectious

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