A Necrotic Ulcer in an Extremely Premature Infant

A 9-day-old boy born at 24 0/7 weeks' gestation with a large necrotic area in the right malar region.Born to a 22-year-old primigravida woman.Prenatal course notable for maternal tobacco and marijuana use.Estimated gestational age: 24 0/7 weeks.Spontaneous vaginal delivery with preterm premature rupture of membranes due to unstoppable labor.Apgar scores: 2, 4, and 8 at 1, 5, and 10 minutes, respectively.Infant is intubated in the delivery room due to respiratory distress and brought to the NICU for further care.Birthweight: 629 g (41 percentile).Birth length: 13 in (33 cm) (85 percentile).Birth head circumference: 8.3 in (21 cm) (28 percentile).At 9 days of age, the infant had an unplanned extubation, followed by reintubation, that led to a skin laceration, which appears like a small abrasion that was scabbed, on the infant's right malar region. After the endotracheal tube tape was retaped 3 days later, this area appears necrotic, covering a larger area than the initial abrasion. The NICU team orders a complete blood cell count and blood culture, and the infant is started on vancomycin and cefepime. The white blood cell count is 8,810/μL (8.81 × 109/L), with a differential count of 35% neutrophils, 3% bands, 23% lymphocytes, 23% monocytes, 3% metamyelocytes, 3% myelocytes, and 1% varying other cell types. The infant's hemoglobin level is 10.8 g/dL (108 g/L), with a platelet count of 76 × 103/μL (76 × 109/L). The following day, the infant is transferred to our hospital for evaluation by plastic surgery and pediatric infectious diseases.Heart rate: 158 beats/min.Respiratory rate: 30 breaths/min.Blood pressure: 81/43 mm Hg.Oxygen saturation: 100% on high-flow oscillator ventilator (fraction of inspired oxygen, 1.0; mean airway pressure, 15 mm Hg; Hertz, 13; amplitude, 28).General: Small-for–gestational age infant, intubated and sedated.Head: Normocephalic; normal, open, flat fontanelles; symmetrical facies; patent nares; intact palate; no neck mass or crepitus.Oral cavity: Pink mucosae, intact palate, no lymphadenopathy.Lungs: Symmetrical chest rise, bilateral and equal ventilator sounds.Cardiovascular: Normal S1, S2 heart sounds; regular rate and rhythm; grade I/VI murmur, capillary refill time of 4 seconds, femoral pulses equal and strong.Abdomen: Normal bowel sounds; no hepatosplenomegaly; nondistended, nontender.Genitourinary: Normal preterm male genitalia; patent anus.Skeletal: Spine appears normal.Skin: 2x2-cm necrotic ulcer on the right malar region with visible base and clear drainage (Fig 1).Neurologic: sedated.A repeated blood culture is sent along with a wound culture. The plastic surgery team recommends deferring surgery and pursuing medical management. The pediatric infectious diseases team recommends the addition of fluconazole for possible fungal infection. All blood culture results are negative. The wound culture results are reported at 18 days of age with growth of Enterococcus faecalis and Candida albicans, prompting adjustment of the antimicrobial regimen to piperacillin-tazobactam and fluconazole. At 22 days of age, the necrotic ulcer sloughs off, resulting in decreased subcutaneous and deep tissue at the ulcer site (Fig 2), and the tissue is sent for culture and pathologic examination.Facial necrotic ulcer in a preterm infant.Ecthyma gangrenosum (EG).Cutaneous mucormycosis.Necrotizing fasciitis.Initially, the patient is diagnosed as having EG due to the positive wound culture growing E faecalis and C albicans, which are common organisms of EG. (1) However, the wound culture from the necrotic tissue grows E faecalis, C albicans, and Rhizopus species. Furthermore, the pathology report demonstrates necrotic tissue with numerous fungal hyphae morphologically suggestive of mucormycosis (Fig 3), prompting the definitive diagnosis of cutaneous mucormycosis with superimposed E faecalis and C albicans infection.Based on these results, piperacillin-tazobactam and fluconazole are discontinued and intravenous deoxycholate amphotericin B is initiated. When the infant is 51 days old, plastic surgery performs a punch biopsy of the wound margin to ensure that the infection is cleared. At 79 days of age, the biopsy culture from the wound margins finalizes as negative, and deoxycholate amphotericin B is discontinued. This patient receives 56 days of treatment with deoxycholate amphotericin B for cutaneous mucormycosis and never requires surgical debridement.The patient is successfully discharged from the NICU at 104 days of age on home oxygen via low-flow cannula for chronic lung disease and ad lib feedings. His physical examination at that time shows a well-healed right malar region with scar (Fig 4). One month after discharge, he is evaluated by pediatric plastic surgery. Plastic surgery plans to evaluate annually for a few years to assess for the development of impaired tissue growth due to scar tissue and whether fat grafting will be indicated. At the time this manuscript was written, the patient did not required surgical intervention.Cutaneous mucormycosis is a rare mold infection that most often occurs in immunocompromised patients, frequently in the respiratory tract and skin. (2) Cutaneous infections can result from traumatic wounds, similar to this patient. Other risk factors identified for cutaneous mucormycosis include prematurity, low birthweight, broad-spectrum antibiotic use, and corticosteroid therapy. (3) Common pathogens include Rhizopus, Mucor, Lichtheimia species, and Rhizomucor species. Pathogen identification occurs through histopathologic examination of tissue and culture, both of which were performed in this patient. (2)Deoxycholate amphotericin B is used to initially treat cutaneous mucormycosis, but surgical debridement is typically crucial to ensure that appropriate source control is obtained. (3) Although rare, previous cases of neonatal cutaneous mucormycosis have been reported, and at least 1 case details successful management with amphotericin B alone, similar to our patient. (4)Similar to cutaneous mucormycosis, EG occurs in immunocompromised or critically ill patients. EG is associated with hemorrhagic pustules that evolve into necrotic, gangrenous ulcers with black-gray eschar. (1) These ulcers usually are the sequelae of pathogenic perivascular invasion of vessels that leads to ischemic necrosis. The most common bacterial cause of EG is Pseudomonas aeruginosa, but multiple other pathogens have been reported, including Escherichia coli, Staphylococcus aureus, Streptococcus pyogenes, Aeromonas species, and Citrobacter species. (1)(2)(5) A viral pathogen to consider is herpes simplex virus, whereas fungal pathogens include Candida, Aspergillus, and Fusarium species. (1) E faecalis is not a bacterial cause that has commonly been reported as a cause of EG. Common sites for EG include the axillary and anogenital regions; the arms, legs, trunk, and face are less-often-reported sites. (6)Necrotizing fasciitis, in contrast to cutaneous mucormycosis, can occur in neonates regardless of their immune status and develops secondary to infection (usually polymicrobial). Necrotizing fasciitis is typically associated with tissue edema, rapid progression of inflammation, and hemodynamic instability. (7) Our patient had a more confined infection and did not have evidence of systemic toxicity, making this type of infection less likely.