The patient was a 730 g male born at 28+1 weeks of gestation, the product of a spontaneous dichorionic diamniotic twin pregnancy complicated by severe growth restriction in both fetuses. Leukopenia, thrombocytopenia, and mild bilateral ventriculomegaly were present at birth, which raised suspicion for congenital infection; a urine sample sent on day 12 of life was positive for CMV by culture. Blood work demonstrated very mildly elevated serum conjugated bilirubin (13 micromol/L) on the day of birth that progressively increased; there was no elevation of liver transaminases, increase in prothrombin time, or clinically evident bleeding. CMV infection of both placentas was confirmed using immunohistochemistry and both chronic hemorrhagic lymphoplasmacytic villitis and villous vasculitis was seen on pathology. Consequently, treatment with ganciclovir (6 mg/kg/dose IV q12h) was initiated at 19 days of age. It should be noted that his absolute neutrophil count (ANC) transiently dropped below 1000/microL at 17 days of age, before antivirals were started. On day 2 of ganciclovir treatment, the ANC decreased again to 800/microL, which resulted in a 36-hour suspension of antiviral therapy.
At just under 5 weeks chronologic age, after 13 days of ganciclovir therapy, when his absolute neutrophil count was normal, the patient developed sepsis in association with an Enterococcus faecalis central line infection. The peripherally-inserted central catheter was not removed promptly, his neutrophil count briefly dropped to 400/microL, the ganciclovir was held, and he experienced a pulmonary haemorrhage four days later. With antibacterial therapy and removal of the offending venous catheter, his condition rapidly stabilized. His plasma CMV viral load (VL) was determined to be 1 × 106 copies/mL after eleven days off treatment; ganciclovir treatment was resumed after a two-week hiatus and continued for an additional 6 weeks through a replacement central venous catheter. Due to the neutropaenia associated with his septic deterioration, filgrastim (granulocyte colony stimulating factor) therapy was begun the day prior to the reinitiation of ganciclovir therapy and was given intermittently whenever the patient’s neutrophils appeared to be in decline, though the ANC did not go below 1000/microL during the remainder of the ganciclovir treatment course.
During this time, the baby was mainly fed with frozen-thawed breast milk. For prematurity-associated anaemia, he was transfused a total of 785 mL (4 donors) of leukoreduced irradiated blood, of which only 341 mL (2 donors) was received when not on ganciclovir therapy.
Three weeks after finishing the ganciclovir, at 4 months chronologic age, shortly before the time of his planned hospital discharge, the infant developed progressive respiratory distress. Cefazolin and gentamicin were started; blood cultures were negative, and, at this time, the absolute neutrophil count was normal. He was stable enough to be electively intubated for laser eye surgery, but subsequently developed increased respiratory requirements. His chest X-ray showed bilateral mixed airspace and interstitial opacities, an endotracheal tube aspirate showed ‘few’ WBCs on the gram stain, and aspirate cultures grew K. pneumoniae (sensitive to cefazolin), so a presumptive diagnosis of ventilator-associated pneumonia was made. The cerebrospinal fluid was sampled and was found to have 13 WBC/hpf (2% neutrophils, 48% lymphocytes, 50% monocytes), 2 RBC/hpf, glucose of 2.8 mmol/L, and protein of 1.3 g/L. His condition worsened, and he was switched to cefotaxime, without demonstrable improvement. He developed respiratory failure requiring ventilation with high frequency oscillatory ventilation and nitric oxide therapy was initiated. Significant hepatosplenomegaly was observed for the first time, accompanied by elevated AST and ALT (273 U/L and 221 U/L, respectively), and the patient developed disseminated intravascular coagulation. Repeat bacterial cultures of blood, urine and cerebrospinal fluid were negative. Given the pneumonitis, massive hepatosplenomegaly, thrombocytopenia, coagulopathy, and lack of response to cefotaxime, CMV was suspected to be the causative pathogen. Urine and endotracheal aspirate cultures for CMV were positive, plasma CMV polymerase chain reaction (PCR) showed a VL of 3 × 106 copies/ml, and CMV was detected in the CSF by PCR. Cefotaxime was discontinued and ganciclovir therapy was reinitiated (6 mg/kg/dose IV q12h) 14 days after the onset of his deterioration; slow improvements in respiratory status and thrombocytopenia were then observed. After 13 days of therapy, the infant was stable from a cardiopulmonary perspective; his CMV plasma VL at that time was 1865 copies/mL. The patient continued to improve and after 4 weeks of IV therapy he was switched to oral valganciclovir (16 mg/kg/dose q12h) when he no longer required intravenous access for any other indication.
He was discharged home three weeks later, on valganciclovir, at 6 months of chronologic age, still requiring low flow oxygen; at this time, his CMV plasma VL was 5771 copies/mL. The decision was made to continue oral antiviral therapy after discharge until his viral load became undetectable, given his complicated history; ultimately, he received 9 weeks of oral therapy and
3 months total therapy. He did not experience any significant complications thought to be caused by his second treatment course of ganciclovir/valganciclovir; his absolute neutrophil count hit a nadir of 900/microL but recovered without any filgrastim treatment or alteration to antiviral dosing. Laboratory evaluation for immune deficiency performed at 11 months chronologic age demonstrated that his immunoglobulin A level was 0.31 g/L, immunoglobulin G level was 14.6 g/L, and immunoglobulin M level was 0.95 g/L. The patient’s CD4 count was 1530/microL (30%), CD8 count was 1580/microL, and he had 23% CD19 B cells. Phytohemagglutinin stimulation testing of T lymphocytes revealed a normal response.