Ejaz A Khan, Shabana Naz, Musarrat Hussain, Shaukat A Bangash.
Liposomal Amphotericin B in a premature neonate with fatal disseminated Histoplasmosis - a case report and review of literature.
Infect Dis J Jan ;10(2):15-7.
A two-hour-old premature second twin male neonate was referred from a private nursing home because of respiratory distress. This was a twin pregnancy delivered by spontaneous vaginal delivery at 32 weeks gestation. Apgar score was not known and birth weight was 1.25 kg. He had no respiratory effort and was intubated. He was administered intravenous epinephrine and bicarbonate. He recovered with return of spontaneous respiration. However, because of increasing respiratory distress he was referred for mechanical ventilation to this hospital. This pregnancy was conceived after eight years by In Vitro Fertilization in London. The mother had gestational diabetes that was controlled on insulin. She had regular antenatal care with no history of infections, rash, vaginal bleeding or discharge, drug abuse or prolonged rupture of membranes. Twin 1 male had birth weight of 1.8 kg and had mild respiratory distress. This neonate remained well and was discharged after 6 days. On physical examination at time of admission this second twin had moderate respiratory distress with grunting. Pulse was 140/minute, respiratory rate 60/minute, temperature 980 F and oxygen saturation 70% on room air. There were no dysmorphic features. Anterior fontanelle was soft. Oropharynx was clear. Chest examination revealed few bilateral coarse crepitations with subcostal and intercostal retractions. There was no heart murmur or hepatosplenomegaly. There were nonspecific bruises on both arms. Neuorologic examination was normal. Initial laboratory evaluation showed WBC count 7,100/dl (neutrophils 30%, lymphocytes 65%, monocytes 3%), hemoglobin 19g/dl, platelets 123,000/dl. Blood culture was negative. Chest xray showed changes consistent with hyaline membrane disease. The neonate was intubated and started on mechanical ventilation. Intravenous ampicillin and gentamicin were initiated and given for seven days. There was gradual improvement and the neonate was extubated after 3 days. Dexamethasone was given for 24 hours before and 72 hours after extubation. On day 9 of hospitalization the neonate had apnea and bradycardia. Physical examination showed a listless and unresponsive neonate. Bilateral crepitations were noted on chest examination. There was no heart murmur. The liver and spleen were palpable 2 cm below the costal margins. Resuscitation was done with suctioning and ambu bagging. Oxygen was given via oxyhood. Vancomycin, amikacin and ceftazidime were initiated after cultures were taken. Sepsis evaluation showed WBC count 21,600/dl (neutrophils 80%, lymphocytes 10%, monocytes 10%), hemoglobin 18g/dl, platelet count of 28,000/dl. The peripheral film showed marked toxic granulation and dimorphic fungus most likely consisting with histoplasma capsulatum. This finding was disregarded as possible contamination in the sample tube for 48 hours. Chest xray showed an infiltrate on the right side. Cerebrospinal spinal fluid (CSF) analysis showed WBC 200/dl (neutrophils 80%, lymphocytes 10%), protein 140mg/dl, glucose 73mg/dl. Gram stain and culture of CSF revealed no organisms. However, three consecutive day blood cultures and a fungal culture revealed growth of histoplasma capsulatum. The second, third and fourth blood culture also grew enterobacter species. The fifth blood culture revealed growth of enterobacter species. Urine culture was not sent. An ultrasound of the head and abdomen was normal. An echocardiogram showed large patent ductus artereosis (PDA), left to right shunt, a small subaortic vetricular septal defect but no vegetations. Examination of the eye by ophthalmologist showed bilateral multiple choroidal infiltrates consistent with pan-uveitis. Platelets were transfused and indomethacin was given for PDA. A followup echo showed, however, the PDA as patent. Furosimide was given but a repeat course of indomethacin was delayed. The antibiotics were adjusted after the blood culture reports and susceptibilities. Meropenem was added to amikacin. Vancomycin and ceftazidime were discontinued. Conventional amphotericin B (Fungizone(r)) was initiated with a dose of 1 mg/kg/day on first day and then replaced with Liposomal amphotericin B (AmBisome(r)) at 5 mg/kg/day. Total cumulative dose of amphotericin B given was 35 mg/kg. Electrolytes and renal function were monitored and remained normal. The clinical condition improved after three days. The neonate however remained oxygen dependent. Nasogastric feeding was started and weight improved to 1.7kg. The source of this infection could not be determined. There was construction within the hospital but in a remote area of the hospital. There were no new cases in the neonatal intensive care unit or other parts of the hospital 18 months after this episode. The other twin remained healthy. The mother was asymptomatic and was not screened. Contaminant intravenous fluid or medicines is a possibility especially with concurrent Enterobacter sepsis but was not investigated initially by culture of the intravenous drips. The neonate was shifted to another hospital on parent`s request because of cost of the care in the intensive care unit on day of 1ife 20th. They were advised to continue with meropenem and amikacin for a total of days from last positive blood culture Liposomal amphotericin B was to be given for total cumulative dose of 50 mg/kg. PDA ligation was also advised once the neonate was more stable. The antibiotics and liposomal amphotericin B were continued. However the neonate died after transfer to the other hospital on day of life 25th possiblly because of ongoing sepsis and heart failure.
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