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Clinical Therapeutics

Intrahepatic Administration of Liposomal Amphotericin B (Ambisome) for the Management of a Liver Abscess from Candida albicans in a Preterm Infant

Cinzia Auriti, Maria Paola Ronchetti, Iliana Bersani, Fabrizio Gennari, Fiammetta Piersigilli
Cinzia Auriti
aDepartment of Medical and Surgical Neonatology, Bambino Gesù Children’s Hospital, Rome, Italy
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Maria Paola Ronchetti
aDepartment of Medical and Surgical Neonatology, Bambino Gesù Children’s Hospital, Rome, Italy
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Iliana Bersani
aDepartment of Medical and Surgical Neonatology, Bambino Gesù Children’s Hospital, Rome, Italy
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  • ORCID record for Iliana Bersani
Fabrizio Gennari
aDepartment of Medical and Surgical Neonatology, Bambino Gesù Children’s Hospital, Rome, Italy
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Fiammetta Piersigilli
aDepartment of Medical and Surgical Neonatology, Bambino Gesù Children’s Hospital, Rome, Italy
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DOI: 10.1128/AAC.01239-18
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ABSTRACT

Hepatic fungal abscesses are rare in the neonatal period and often constitute a severe complication of the catheterization of the umbilical vessels. Such life-threatening lesions are observed more frequently in preterm than in other newborn infants and the optimal treatment remains uncertain. We present the case of a preterm neonate, who developed an intrahepatic lesion due to parenteral extravasation, successively contaminated by Candida albicans. Despite the maximal pharmacological therapies, the treatment that led to the definitive resolution of the abscess was the placement of surgical drainage followed by the direct intralesional administration of liposomal amphotericin B (Ambisome), never described in neonates in the literature, which turned out to be a safe and effective approach.

TEXT

Fungal liver abscesses are uncommon in neonates. The diagnosis is challenging because the clinical signs may be subtle in the early stages, requiring a high degree of suspicion and an abdominal ultrasound (US) screening in case of a septic neonate with a history of vascular catheterization. Mortality is elevated due to the difficult resolution of the abscess by medical therapy alone. Until now, the scientific literature reported only a few cases of neonatal hepatic fungal abscesses, mainly in preterm neonates (1–3). To the best of our knowledge, there are no data about direct intralesional administration of liposomal amphotericin B to treat such fungal abscesses, neither in neonates nor in children. In adults, intraportal administration of amphotericin B has occasionally been described in patients with hematological malignancies (4–6).

We report the case of a Candida albicans liver abscess secondary to parenteral nutrition extravasation through the umbilical venous catheter in a preterm neonate with life-threatening clinical presentation. The liver abscess was resistant to both systemic antifungal therapy and surgical drainage. Finally, it was successfully treated by adding direct intralesional administration of liposomal amphotericin B to the already ongoing therapies.

Case report.A preterm neonate (gestational age, 28 weeks; body weight, 1,000 g; Apgar score, 7 to 8) was born from twin pregnancy by cesarean section due to life-threatening labor. The baby was intubated at birth and treated with surfactant, and an umbilical venous catheter (UVC) was placed for parenteral nutrition and drug administration. At 20 h of life, the baby was extubated and ventilated by nasal continuous positive airway pressure.

On the 8th day of life (DOL), clinical conditions worsened, the baby required reintubation and mechanical ventilation, and the UVC was replaced by a central venous catheter (CVC) through the left arm. On DOL 12, a right abdominal tender elastic mass (d = 48 × 50 mm) with perihepatic fluid was detected by abdominal ultrasound (US) and computed tomography (CT) scanning. Therefore, the baby was referred to our neonatal intensive care unit (NICU). At admission, abdominal US and CT scans showed an intrahepatic, ovalar, tender mass (d = 65 × 45 × 35 mm) that appeared multilobulate with a nonuniform colliquated core and occupied most of the right hepatic lobe, with dislocation of the hepatic vessels and gallbladder (Fig. 1A, B, C). Presumably, parenteral nutrition extravasation through the UVC represented the causative mechanism, with subsequent hemorrhagic infarction. Neonatal conditions were severe; the neonate was mechanically ventilated and assisted with inotropes. A two-lumen CVC through the left jugular vein was placed. On DOL 17, respiratory and cardiocirculatory conditions critically worsened, and peripheral and CVC blood cultures turned positive for C. albicans. Susceptibility tests were performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines M27-A3 (7) and M27-S4 (8). The isolated Candida strain was susceptible to micafungin (MIC, 0.015 µg/ml), anidulafungin (MIC, 0.03 µg/ml), fluconazole (MIC, 0.25 µg/ml), itraconazole (MIC, 0.06 µg/ml), and voriconazole (MIC, <0.008 µg/ml) and wild type to amphotericin B (MIC, 0.5 µg/ml). Among the effective antifungals, we chose micafungin because our NICU developed a method for monitoring plasma concentrations of such drugs via heelstick microsampling and the baby did not present with liver failure (9). Therefore, we promptly started intravenous micafungin (Mycamine 8 mg/kg daily), but no improvement in clinical conditions was achieved. Peripheral and CVC blood cultures continued to be positive after 14 days of micafungin therapy, despite CVC replacement and micafungin blood concentrations within therapeutic ranges (10), i.e., 3.1, 18.0, 16.0, and 10.4 µg/ml 1 h before and 1, 2, and 8 h after infusion. Because the infection persisted, we added intravenous liposomal amphotericin B (3 to 5 mg/kg daily) to micafungin and started the lock therapy of CVC with micafungin (5 mg/liter in 70% ethanol, closing each lumen for 12 h) (11), with the aim to preserve the CVC considering the critical conditions. Due to continued positive blood cultures, the CVC was newly replaced, but blood cultures once more remained positive for C. albicans, and clinical conditions did not improve. US scans of the brain, kidneys, and spleen and echocardiography did not detect localizations of the infection or endocardial vegetation that could justify the persistence of the fungemia. On DOL 25, due to an increasing amount of ascitic fluid, a tunneled intraperitoneal catheter (Argyle, 43 cm) was placed, which resulted in the exit of ∼100 ml of citrine liquid. However, the clinical conditions again did not improve, blood cultures were persistently positive, and peritoneal fluid grew the same species of C. albicans. On DOL 35, suspecting a Candida superinfection of the preexisting hepatic lesion, after obtaining informed consent for the procedure from the patient's parents, we placed an intralesional 6F pigtail catheter under US guidance; as expected, 4 ml of purulent material was drained, and this grew C. albicans (Fig.1E). Therefore, we decided to administer 5 ml of amphotericin B diluted in 0.9% saline solution (1 mg/ml) once daily directly inside the liver abscess, closing the pigtail catheter for 30 min. Ten days later, blood and intralesional fluid cultures were finally negative, and neonatal conditions progressively improved. The intrahepatic lesion appeared markedly reduced at the next hepatic US assessment (d = 27 × 35 × 32 mm). The entire course of intravenous antifungal therapy lasted 4 weeks. Brain magnetic resonance imaging detected a bilateral subependymal hemorrhage, but the neurologic development of the baby at the 6-month follow-up was normal for the corrected chronological age.

FIG 1
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FIG 1

(A) X-ray imaging showing an intrahepatic lesion caused by parenteral nutrition extravasation through the umbilical venous catheter. Ultrasound (B), Doppler (C), and computed tomography (D) imaging showing an ovalar intrahepatic lesion involving the right lobe, with dislocation of the hepatic vessels and gallbladder. (E) X-ray imaging showing the left peritoneal catheter and intrahepatic drainage.

Fungal liver abscesses are rare during the neonatal period and often constitute a severe complication of umbilical vessel catheterization, central parenteral nutrition catheters, necrotizing enterocolitis, and prematurity. Untreated, they lead to serious clinical sequelae and high mortality rates (12).

Preterm infants are more predisposed than others in relation to physiological immunodeficiency and prolonged exposure to NICU risk factors, such as invasive procedures to resistant nosocomial germs requiring prolonged antibiotic therapies and steroids.

Currently, liver abscesses in adult patients are treated with antibiotics along with percutaneous needle aspiration or percutaneous catheter drainage, and surgical drainage is used only in patients who fail to respond to such treatment. In abscesses >5 cm, catheter drainage performs better than repeated needle aspiration (13). In neonates, the optimal treatment of fungal liver abscesses is still uncertain, and clinical experiences are poor and limited to sporadic reports (1–3). The difficulties of repeated needle aspirations in infants with very low weight (our patient weighed 1.4 kg) and the underlying severe clinical conditions should be considered.

The diagnosis of liver abscess is difficult at first and requires a high degree of suspicion, especially in neonates with very low birth weight. In the early stage of abscess formation, radiography is not conclusive. In the more advanced stages, the suspicion may arise due to the presence of intralesional air, which is revealed by radiographic examination of the abdomen. The availability of US has been an important step toward diagnosis of this condition because it allows for repeatable, noninvasive screening in case of suspicion; guarantees an early diagnosis; and, in relation to this precocity, offers a higher survival rate. CT scan is the definitive tool for the diagnosis of hepatic abscesses.

The baby described in the present case report was transferred to our NICU with a suspected hepatic abscess, so we did not have firsthand knowledge of the medical situation. It was difficult to achieve infection resolution because the abscess was extensive and probably constituted a continuous source of contamination also of the peritoneum, where C. albicans was also present; and the drugs administered systemically could not penetrate the lesion in concentrations sufficient to sterilize it. In our case, the placement of an echo-guided catheter into the hepatic abscess and the intralesional administration of liposomal amphotericin B allowed the resolution of a critical life-threatening situation that had not responded to any other intensive treatment. Further investigations are required to confirm such practice in neonates.

ACKNOWLEDGMENTS

We have no conflicts of interest in connection with this paper. No honorarium, grant, or other form of payment was given to anyone to write the manuscript.

Parents’ informed consent was requested before each nonemergency care procedure. Parents also consented to the publication of their child’s history and clinical data.

FOOTNOTES

    • Received 14 June 2018.
    • Returned for modification 2 August 2018.
    • Accepted 2 September 2018.
    • Accepted manuscript posted online 17 September 2018.
  • Copyright © 2018 American Society for Microbiology.

All Rights Reserved.

REFERENCES

  1. 1.↵
    1. Sharma D,
    2. Choudhary M,
    3. Shastri S,
    4. Sharma PK
    . 2015. Neonatal liver abscesses due to Candida infection in a preterm infant, secondary to malpositioned umbilical lines–a rare entity. Pathog Glob Health 109:84–87. doi:10.1179/2047773215Y.0000000008.
    OpenUrlCrossRef
  2. 2.↵
    1. Cascio A,
    2. Pantaleo D,
    3. Corona G,
    4. Barberi G,
    5. Delfino D,
    6. Romeo O,
    7. Iaria C,
    8. Barberi I
    . 2014. Neonatal liver abscesses associated with candidemia: three cases and review of literature. J Matern Fetal Neonatal Med 27:743–749. doi:10.3109/14767058.2013.837878.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Filippi L,
    2. Poggi C,
    3. Gozzini E,
    4. Meleleo R,
    5. Mirabile L,
    6. Fiorini P
    . 2009. Neonatal liver abscesses due to Candida infection effectively treated with caspofungin. Acta Paediatr 98:906–909. doi:10.1111/j.1651-2227.2009.01225.x.
    OpenUrlCrossRefPubMed
  4. 4.↵
    1. Miyazaki H,
    2. Ino T,
    3. Sobue R,
    4. Tuzuki M,
    5. Maeda H,
    6. Nomura T,
    7. Wakita M
    . 1992. Multiple hepatosplenic abscesses: successful treatment by continuous intraportal administration of amphotericin B in a case with acute promyelocytic leukemia. Rinsho Ketsueki 33:1052–1056.
    OpenUrlPubMed
  5. 5.↵
    1. Murayama T,
    2. Ito M,
    3. Imoto S,
    4. Takahashi T,
    5. Matozaki S,
    6. Nakagawa T,
    7. Isobe T
    . 1992. Percutaneous transhepatic intraportal administration of amphotericin B to a patient with multiple liver abscesses due to Candida albicans: with monitoring by fungal index as a parameter of Candida volume. Rinsho Ketsueki 33:82–86.
    OpenUrlPubMed
  6. 6.↵
    1. Ishii H,
    2. Hiruma K,
    3. Morio S,
    4. Hirasawa A,
    5. Wakita H,
    6. Endoh N,
    7. Oh H,
    8. Yoshida S,
    9. Aotsuka N,
    10. Asai T
    . 1990. Multiple liver abscesses due to Candida albicans in a patient with acute promyelocytic leukemia: percutaneous transhepatic intraportal administration of amphotericin B. Rinsho Ketsueki 31:330–334.
    OpenUrlPubMed
  7. 7.↵
    Clinical and Laboratory Standards Institute. 2008. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard—3rd ed. CLSI document M27-A3. Clinical and Laboratory Standards Institute, Wayne, PA.
  8. 8.↵
    Clinical and Laboratory Standards Institute. 2012. Reference method for broth dilution antifungal susceptibility testing of yeasts; 4th informational supplement. CLSI document M27-S4. Clinical and Laboratory Standards Institute, Wayne, PA.
  9. 9.↵
    1. Auriti C,
    2. Goffredo BM,
    3. Ronchetti MP,
    4. Piersigilli F,
    5. Cairoli S,
    6. Bersani I,
    7. Dotta A,
    8. Pai MP
    . 2018. Validation of heel stick microsampling to optimize micafungin doses in neonates and young infants. Antimicrob Agents Chemother 62:e01199-18. doi:10.1128/AAC.01199-18.
    OpenUrlAbstract/FREE Full Text
  10. 10.↵
    1. Auriti C,
    2. Falcone M,
    3. Ronchetti MP,
    4. Goffredo BM,
    5. Cairoli S,
    6. Crisafulli R,
    7. Piersigilli F,
    8. Corsetti T,
    9. Dotta A,
    10. Pai MP
    . 2016. High-dose micafungin for preterm neonates and infants with invasive and central nervous system candidiasis. Antimicrob Agents Chemother 60:7333–7339. doi:10.1128/AAC.01172-16.
    OpenUrlAbstract/FREE Full Text
  11. 11.↵
    1. Piersigilli F,
    2. Auriti C,
    3. Bersani I,
    4. Goffredo B,
    5. Bianco G,
    6. Savarese I,
    7. Dotta A
    . 2014. Antifungal lock therapy with combined 70% ethanol and micafungin in a critically ill infant. Pediatr Infect Dis J 33:419–420. doi:10.1097/INF.0000000000000116.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Mathis RK,
    2. Andres JM,
    3. Walker WA
    . 1977. Liver disease in infants. Part II: hepatic disease states. J Pediatr 90:864–880. doi:10.1016/S0022-3476(77)80553-2.
    OpenUrlCrossRefPubMedWeb of Science
  13. 13.↵
    1. Cai Y-L,
    2. Xiong X-Z,
    3. Lu J,
    4. Cheng Y,
    5. Yang C,
    6. Lin Y-X,
    7. Zhang J,
    8. Cheng N-S
    . 2015. Percutaneous needle aspiration versus catheter drainage in the management of liver abscess: a systematic review and meta-analysis. HPB (Oxford) 17:195–201. doi:10.1111/hpb.12332.
    OpenUrlCrossRef
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Intrahepatic Administration of Liposomal Amphotericin B (Ambisome) for the Management of a Liver Abscess from Candida albicans in a Preterm Infant
Cinzia Auriti, Maria Paola Ronchetti, Iliana Bersani, Fabrizio Gennari, Fiammetta Piersigilli
Antimicrobial Agents and Chemotherapy Nov 2018, 62 (12) e01239-18; DOI: 10.1128/AAC.01239-18

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Intrahepatic Administration of Liposomal Amphotericin B (Ambisome) for the Management of a Liver Abscess from Candida albicans in a Preterm Infant
Cinzia Auriti, Maria Paola Ronchetti, Iliana Bersani, Fabrizio Gennari, Fiammetta Piersigilli
Antimicrobial Agents and Chemotherapy Nov 2018, 62 (12) e01239-18; DOI: 10.1128/AAC.01239-18
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KEYWORDS

liver abscess
liposomal amphotericin B
Candida albicans

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