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 Table of Contents  
CASE REPORT
Year : 2017  |  Volume : 6  |  Issue : 2  |  Page : 94-96

Successful medical treatment of Candida albicans endocarditis in an extremely low birth weight infant


Department of Pediatrics, Pediatric and Neonatal Intensive Care Unit, Bufalini Hospital, Cesena, Italy

Date of Web Publication13-Apr-2017

Correspondence Address:
Vittoria Rizzo
Pediatric-Neonatal Intensive Care Unit, Bufalini Hospital, V.le Ghirotti 286, 47521 Cesena FC
Italy
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcn.JCN_195_15

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  Abstract 

Fungal endocarditis is an uncommon complication of invasive fungal infections and is associated with high burden of morbidity and mortality. It frequently occurs in premature infants, and Candida albicans is the predominant fungal agent. We report a case of a female neonate, born at 27 weeks of gestation, who developed during the 2nd week of life candidemia and endocardic vegetation. Initially treated with fluconazole, she received caspofungin combined with liposomal amphotericin B and subsequently micafungin plus low-dose heparin. We observed the complete resolution of the vegetation 7 weeks after the end of the treatment.

Keywords: Echinocandins, extremely low birth weight infant, fungal endocarditis


How to cite this article:
Cuna CD, Rizzo V, Malaigia L, Biasini A. Successful medical treatment of Candida albicans endocarditis in an extremely low birth weight infant. J Clin Neonatol 2017;6:94-6

How to cite this URL:
Cuna CD, Rizzo V, Malaigia L, Biasini A. Successful medical treatment of Candida albicans endocarditis in an extremely low birth weight infant. J Clin Neonatol [serial online] 2017 [cited 2019 Nov 15];6:94-6. Available from: http://www.jcnonweb.com/text.asp?2017/6/2/94/204511


  Introduction Top


Fungal endocarditis (FE) may complicate 5% of invasive fungal infections (IFIs) in neonates; Candida albicans is the predominant fungus.[1],[2] Detection of an endocardiac mass and of positive blood culture suggest the diagnosis. Definite diagnosis requires surgical removal, pathological and microbiological examination of the mass. Reported mortality is up to 42.2%.[1]


  Case Report Top


A female neonate, born at gestational age 27 weeks weighing 800 g, was admitted to our neonatal Intensive Care Unit (NICU). On admission, she was mechanically ventilated, treated with surfactant; umbilical venous catheter (UVC) was placed, and its tip was demonstrated by chest radiograph in the right atrium (RA). Minimal enteral feeding was started on day 1 with human donor bank milk and own mother milk. Fluconazole prophylaxis was not administered. On day 2 was estubated to nasal continuous positive airway pressure (CPAP). On day 7, full enteral feeding was achieved, parenteral nutrition stopped, and UVC removed. Initially leukopenic (lower leukocyte count was 3.43 × 109/L on day 1) and thrombocytopenic (lower platelet count was 22 × 109/L on day 5), the baby had normal leukocyte count on day 6, with platelet count rising to 57 × 109/L. Ampicillin and amikacin started on day 1 where administered for a total of 6 days.

Echocardiogram (ECHO) on day 4 revealed a patent ductus arteriosus (PDA) with left-sided volume overload, no structural abnormalities or vegetations; oral paracetamol was administered for 5 days with initial good response.

On day 9, the baby presented with mild apnea episodes and a single boil on the abdomen; C-reactive protein was 43.8 mg/L and immature/total (I/T) ratio 0,25, platelet count 82 × 109/L; blood culture was repeated, vancomycin and cefotaxime were started. On day 11, C. albicans grew from blood collected on day 9; it was susceptible in vitro to fluconazole (MIC 0.5), to voriconazole (MIC 0.015), and to amphotericin B (MIC 0.25), other antifungal agents were not tested. On day 11, there was a concurrent clinical deterioration (irritability and need for mechanical ventilation) with platelet count lowered to 30 × 109/L. Lumbar puncture was not performed because of clinical instability. Fluconazole was started (12 mg/kg/d mainly intravenously and for a few days, orally), and antibiotics were stopped. The baby clinically improved and was extubated to nasal CPAP. On day 18, blood culture was still positive for C. albicans.

ECHO on day 24 showed in the upper part of the RA, a fixed round mass measuring 4 mm × 4 mm with a mobile “tail” 10 mm long. The tail protruded into the right ventricle through the tricuspid valve. Diagnosis of FE was made according to the modified Duke's criteria.[3]

Fluconazole was stopped, and echinocandin treatment started, with caspofungin (2 mg/kg every 24 h intravenously) for 4 weeks followed by micafungin (10 mg/kg every 24 h intravenously) for 2 weeks. Blood culture performed 2 days after starting caspofungin treatment resulted negative.

On the repeated ECHOs, the vegetation size remained unchanged, the mobile “tail” protruding either into the right ventricle or into the left atrium through a patent foramen ovale [Figure 1]. PDA became hemodynamically significant with severe left-sided volume overload and was surgically ligated on day 35.
Figure 1: It is represented the fixed round mass (indicated by the thick arrow) in the right atrium, with a large tail (indicated by the thin arrow) protruding, through the foramen ovale, into the left atrium

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On day 45, liposomal amphotericin B (5 mg/kg/d intravenously) was started, together with low-dose heparin (enoxaparin 2 mg/kg, q 12 h, subcutaneously) for anticoagulation. Liposomal amphotericin B was discontinued after 1 week due to worsening anemia. On day 66, the baby was well-appearing, despite unmodified ECHO findings, and treatment with low-dose heparin, and micafungin was stopped. No bleeding events occurred.

A new ECHO performed 7 weeks later showed only residual thickening of part of the interatrial septum with no cardiac vegetations.


  Discussion Top


IFI is an important cause of mortality and morbidity in very low birth weight (VLBW) infants. There is a huge variability in incidence among different neonatal setting.[4] This could be influenced by difficulties in detection of infection, as well as differences in antibiotic treatments protocols, feeding practices, and vascular access policies.

Fluconazole prophylaxis has decreased the incidence of IFI in VLBW infants. It is recommended in infants at higher risk for IFI, matched with a continuous surveillance of fungal ecology.[4] In our NICU, at the time of the reported case, fluconazole prophylaxis was reserved to infants weighing <700 g at birth because the incidence of IFI among VLBW was low (0.6% of all VLBW admitted). Soon after the reported case, we reviewed our protocol extending fluconazole prophylaxis to all infants weighing <1000 g at birth.

Up to 5% of IFI among neonates are complicated by FE.[2] The RA is the most common vegetation site.[1]

FE is rarely symptomatic, with recurrent episodes of bradycardia and hypotension (probably as a result of right ventricular inflow block); most cases occur without any hemodynamic compromise.[5]

Prematurity, use of central venous catheters, parenteral nutrition, and broad spectrum antibiotics are important factors predisposing to FE.[1]Candida species can adhere to cell surfaces and form three-dimensional community of microorganism encased in an exopolymeric matrix, the biofilm. Within biofilms, the fungal colonies are protected from host immune defenses and antifungal drugs by an external slime of fibrin and extracellular matrix.[5]C. albicans in the biofilm has decreased cell-membrane ergosterol content and is less susceptible to fluconazole and amphotericin, both targeting ergosterol. Unlike these agents, the echinocandins (caspofungin, micafungin, and anidulafungin) are active on cell wall of Candida species through inhibition of B-1,3-glucan synthase.[6] Caspofungin has been used in combination with other antifungal agents in neonatal FE, but its efficacy is controversial. it was effective in nine reported cases,[7] ineffective in other six cases.[8],[9],[10],[11],[12]

Micafungin, currently the only echinocandin authorized by the European Medicines Agency for neonatal use, has been effective on simulated endocardial vegetations (in vitro studies)[6] and in several clinical reports of neonatal IFI.[5] Although it is difficult to separate the effect of each antifungal agents on the clinical course of the reported case, we assume that echinocandins played a special role due to their specific action on biofilm.

Surgical excision of fungal vegetation is indicated in case of risk of disseminated infected emboli, increased mobility of the mass, its progressive enlargement, hemodynamic instability of the neonate. However, similar mortality has been found among surgically treated neonates and those receiving only medical treatment.[1]

Thrombolytic agents, urockinase and more recently, recombinant-tissue plasminogen activator have been reported only in a few cases of neonatal endocarditis.[1] They must be carefully evaluated in preterm neonates due to the risk for bleeding events. In the management of the present case, release of septic emboli and metastatic infection after lysis of vegetation was an additional cause of concern. Low-dose heparin, which acts preventing further deposition of fibrin on thrombus has been used in neonatal and pediatric patients for intracardiac thrombi;[13] it carries risk of bleeding so that patients need to be strictly monitored to detect any sign of hemorrhagic complication.


  Conclusions Top


Complete resolution of FE can be achieved by antifungal agents active on biofilm such as echinocandins. This effect can be observed also after the completion of the antifungal treatment, probably due to the occurrence of spontaneous fibrinolysis.

All efforts in prevention of IFI must be attempted, minimizing antibiotic exposure, duration of vascular access and parenteral nutrition, with early introduction of enteral feeds, as well as using fluconazole prophylaxis in infants featuring the highest risk for IFI.

Acknowledgment

The authors would like to thank Dr. Pasquale Catanzariti for his precious contribution in interpreting the patient echocardiographic findings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Pana ZD, Dotis J, Iosifidis E, Roilides E. Fungal endocarditis in neonates: A review of seventy-one cases (1971-2013). Pediatr Infect Dis J 2015;34:803-8.  Back to cited text no. 1
    
2.
Benjamin DK Jr., Poole C, Steinbach WJ, Rowen JL, Walsh TJ. Neonatal candidemia and end-organ damage: A critical appraisal of the literature using meta-analytic techniques. Pediatrics 2003;112:634-40.  Back to cited text no. 2
    
3.
Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr., Bolger AF, Levison ME, et al. Infective endocarditis: Diagnosis, antimicrobial therapy, and management of complications: A statement for healthcare professionals from the committee on rheumatic fever, endocarditis, and Kawasaki disease, council on cardiovascular disease in the young, and the councils on clinical cardiology, stroke, and cardiovascular surgery and anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America. Circulation 2005;111:e394-434.  Back to cited text no. 3
    
4.
Manzoni P, Mostert M, Castagnola E. Update on the management of Candida infections in preterm neonates. Arch Dis Child Fetal Neonatal Ed 2015;100:F454-9.  Back to cited text no. 4
    
5.
Daftary AS, Patole SK, Whitehall JS. Intracardiac fungal masses in high-risk neonates: Clinical observations. Acta Paediatr 1999;88:1009-13.  Back to cited text no. 5
    
6.
Pai MP, Samples ML, Mercier RC, Spilde MN. Activities and ultrastructural effects of antifungal combinations against simulated Candida endocardial vegetations. Antimicrob Agents Chemother 2008;52:2367-76.  Back to cited text no. 6
    
7.
Odio CM, Araya R, Pinto LE, Castro CE, Vasquez S, Alfaro B, et al. Caspofungin therapy of neonates with invasive candidiasis. Pediatr Infect Dis J 2004;23:1093-7.  Back to cited text no. 7
    
8.
Hesseling M, Weindling M, Neal T. First reported use of caspofungin in an extremely low-birth-weight neonate. J Matern Fetal Neonatal Med 2003;14:212.  Back to cited text no. 8
    
9.
Karatza AA, Dimitriou G, Marangos M, Christofidou M, Pavlou V, Giannakopoulos I, et al. Successful resolution of cardiac mycetomas by combined liposomal amphotericin B with fluconazole treatment in premature neonates. Eur J Pediatr 2008;167:1021-3.  Back to cited text no. 9
    
10.
Sharma J, Nagraj A, Allapathi D, Rajegowda B, Leggiadro R. Fungal endocarditis in a premature infant complicated by a right atrial mycetoma and inferior vena cava thrombosis. Images Paediatr Cardiol 2009;11:6-11.  Back to cited text no. 10
    
11.
Li MJ, Hsueh PR, Lu CY, Chou HC, Lee PI, Chang LY, et al. Disseminated candidemia refractory to caspofungin therapy in an infant with extremely low birth weight. J Formos Med Assoc 2012;111:46-50.  Back to cited text no. 11
    
12.
Ozturk E, Tanidir IC, Guzeltas A, Haydin S. Surgical treatment of giant Candida albicans vegetation of tricuspid valve endocarditis in a preterm baby. Pediatr Neonatol 2015;56:197-9.  Back to cited text no. 12
    
13.
Cetin II, Ekici F, Ünal S, Kocabas A, Sahin S, Yazici MU, et al. Intracardiac thrombus in children: The fine equilibrium between the risk and the benefit. Pediatr Hematol Oncol 2014;31:481-7.  Back to cited text no. 13
    


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