Abdominal Distension with Rapidly Progressing Erythema and Edema of the Left Flank in a Preterm Infant

A 15-day old female preterm infant who is tolerating advancing enteral feedings presents with sudden abdominal distension and erythema and edema of the anterior left side of the chest and abdomen.The neonatology team intubated the newborn in the delivery room, administered intratracheal surfactant, and weaned the infant to low ventilator settings with a fraction of inspired oxygen (FiO2) of 0.21. On arrival at the NICU, the team placed umbilical catheters. As a result of extensive bruising of the entire trunk after a difficult extraction, the neonate was placed under phototherapy. She received a second dose of surfactant at 12 hours of age and underwent extubation on the first day after birth. She needed reintubation on the third postnatal day and received a third dose of surfactant at that time. Six days after birth, the team reattempted extubation, but she had increased respiratory distress and required reintubation, followed by a fourth dose of surfactant. At that time, chest radiography showed pulmonary interstitial emphysema (PIE) and the infant was switched from conventional to high-frequency jet ventilation (HFJV). The PIE was noted to resolve on radiography by 12 days of age.The infant’s postnatal course was also notable for empiric treatment with ampicillin and gentamicin, which was discontinued after 48 hours because results of blood and endotracheal cultures performed at birth were negative. She underwent cranial ultrasonography at 7 and 14 days of age, which demonstrated a stable right-sided intraventricular hemorrhage without ventricular dilation. The umbilical catheters were removed at 11 days of age and replaced with a peripheral right radial arterial line and a left-sided antecubital percutaneous intravenous central catheter (PICC), the tip of which could not be advanced beyond the axilla. Before removal of the umbilical venous line, the infant received a single 15 mg/kg dose of vancomycin per NICU protocol.On the morning of her 15th day, the infant’s total bilirubin concentration suddenly increased to 10.5 mg/dL (179.59 μmol/L) from 4.8 mg/dL (82.10 μmol/L) 2 days earlier, and she was therefore placed under intensive phototherapy. That evening, her urine output decreased and she had a weight gain of 200 g, but her respiratory status remained stable on HFJV, with an FiO2 of 0.30. She was tolerating 80 mL/kg per day of expressed human milk feedings after a feeding advancement of 20 mL/kg per day for the last 3 days and was passing several stools per day.On the morning of her 16th day, the infant developed edema and discoloration of the lateral left regions of the chest wall and abdomen that were associated with abdominal distension (Fig 1). She was hypotensive and had developed anuria.The infant remained on FiO2 0.30 via the HFJV. Her abdominal radiographs were unremarkable, nevertheless her feedings were discontinued because of the concern for possible necrotizing enterocolitis (NEC). The nurse placed a Replogle tube, which subsequently drained dark bilious fluid. At the time of her initial presentation, radiography showed a new lucency in the left axilla in the region of the PICC tip (Fig 2, blue arrow). The team then removed the axillary PICC, which had been functioning appropriately, and sent the tip for culture. In addition, the team sent a blood culture specimen from the arterial line and started treatment with vancomycin, cefotaxime, and clindamycin.Although the abdominal radiographs were unremarkable, the clinical picture of metabolic acidosis, distended and discolored abdomen, and an elevated CRP was concerning for peritonitis associated with necrotic bowel and thus, an exploratory laparotomy was performed. The laparotomy revealed edematous but otherwise normal small and large intestines. However, the inside of the abdominal cavity wall was noted to be edematous as well. On removal of the surgical drapes, the soft tissue involvement had dramatically increased, extending to the right side and involving additional layers of the skin (Fig 3). The team added ampicillin for additional Streptococcus coverage and also administered intravenous immunoglobulin.The team treated the infant’s metabolic acidosis and hyperkalemia with sodium bicarbonate, calcium, and insulin-glucose pushes. After the administration of normal saline boluses, a dopamine drip was initiated to manage the infant’s hypotension. She received several blood products as a result of a coagulopathy, thrombocytopenia, and anemia. The infant’s serum creatine phosphokinase was elevated to 1,222 IU/L (normal 38–173 IU/L), indicating skeletal muscle involvement. Blood, endotracheal tube, PICC tip, skin, and a lateral left flank abscess aspirate all grew Enterococcus faecalis, which is sensitive to both ampicillin and vancomycin; the Table shows the culture results. The infant was subsequently transferred to a regional burn center at 19 days of age to manage the excessive skin necrosis (Fig 4). At the time of this writing, the patient has required 3 surgical debridements and has developed bilateral periventricular leukomalacia.Necrotizing fasciitisThis preterm infant presented with a rapidly progressive and necrotizing soft-tissue process suggestive of necrotizing fasciitis. The blood and endotracheal cultures obtained soon after birth were negative and the placenta showed no evidence of chorioamnionitis. Between birth and 8 days of age, the infant had 4 normal CRP levels. The timing of this infant’s presentation is consistent with late-onset sepsis. The onset of this infection might have been on the 15th day of age when the total bilirubin rose abruptly. At that time, the infant was tolerating advancing enteral feedings, passing an appropriate number of stools, and was stable on HFJV with a stable FiO2. Thus, there was no reason to suspect an infection. Necrotizing soft-tissue infections include cellulitis, fasciitis, and myonecrosis. Cellulitis extends into the deep dermis, whereas the latter 2 involve the subcutaneous tissue/deep fascia and underlying muscle, respectively. The unusual flank edema on presentation in combination with the anuria, weight gain, and abnormal complete blood cell count and CRP suggested capillary leak from a systemic inflammatory response.Streptococci consist of β-hemolytic Streptococcus pyogenes (Lancefield groups A, B, C, E, F, and G), Enterococcus (formerly called group D Streptococcus), and α-hemolytic Streptococcus viridans and Streptococcus pneumoniae. (1) Within days after birth, enterococci colonize and become part of the normal gastrointestinal flora. The overall colonization rate for infants in NICUs with enterococcal species is 23%. This rate is higher in preterm infants (33% in infants with gestational age <32 weeks vs 10% in infants with gestations of 32 weeks or more) and is inversely related to birthweight (27.5% vs 18.4% in infants with birthweight <2,500 g vs >2,500 g and 40.7% vs 21.1% in infants with birthweight <1,000 g vs >1,000 g). (2) Factors associated with enterococcal bacteremia include age more than 14 days (73% vs 41%), central vascular catheters (77%), NEC (33%), and abdominal distension (21%). (3)In a review of 66 cases of neonatal necrotizing fasciitis, 47 were the result of an omphalitis. The most common site of initial involvement was the abdomen (n=53) followed by the chest (n=7). The initial presentation ranged from a mild rash to erythema, edema, induration, and/or cellulitis. Blood cultures were positive in only 50% of cases and the mortality rate was 59%. (4)The source of the infection in this patient could have been the umbilical catheters that were in place for 10 days, but the infant received prophylactic vancomycin at the time of catheter removal and there was no evidence of an omphalitis. The periumbilical blanching occurred after the onset of left chest wall edema and discoloration. The endotracheal aspirate showed growth of Enterococcus faecalis at age 15 days, but the low number of white blood cells on the Gram stain, normal chest radiograph, and low FiO2 requirement suggested colonization rather than pneumonia. The tissue could also have been compromised from the trauma/bruising at birth, but this is unlikely given the absence of skin breakdown or local perfusion abnormalities before the sudden onset. We cannot know for certain whether the lucency in the axillary region on the chest radiograph was a primary focus as a result of soft-tissue trauma from the attempts to advance the PICC past the axilla, or a secondary focus from hematogenous spread. However, the properly functioning PICC and absence of shoulder or upper extremity edema are perhaps more suggestive of a secondary focus from hematogenous spread.Abdominal discoloration and distension in a high-risk preterm infant is likely peritonitis from NEC, but in the absence of feeding intolerance and radiographic signs of NEC, a soft-tissue infection should be considered. The absence of erythema, induration, or drainage from the umbilicus in this infant is inconsistent with omphalitis. The infant’s elevated creatine phosphokinase is indicative of skeletal muscle involvement and would not be observed in patients with cellulitis, which is a more superficial soft-tissue infection. Furthermore, rapid extension of erythema, swelling, and tissue necrosis are suggestive of spread along the fascial planes and are also not found in infants who have cellulitis, which is more superficial and localized and therefore less progressive.For a discussion about the use of intravenous immunoglobulin and clindamycin in streptococcal necrotizing soft-tissue infections, please refer to our previous report of necrotizing cellulitis of the scalp in a term infant (NeoReviews. 2015;16[2]).