A 10-week-old extremely preterm girl was admitted to our hospital for severe paroxysmal cyanosis and tachypnea. The infant was the product of a 25-week-and-4-day gestation and was a test-tube baby, from a gestational diabetes mother. The pregnancy was otherwise uneventful. A vaginal delivery was performed. The infant was 890 g with Apgar scores of 5, 9, and 9 at 1, 5, and 10 min, respectively. The infant was independent on the oxygen when she was discharged after 58 days of hospitalization with 2,020 g.
At day of life 70, the infant presented with symptoms of poor response and appetite, but her parents did not notice these symptoms. At day of life 72, the infant has symptoms of paroxysmal cyanosis and tachypnea, then was subsequently admitted to our hospital. Upon arrival to our hospital, vital signs were notable for respiratory rate of 70 per minute and heart rate of 170 beats per minute. Physical exam revealed coarse breath sounds and pulmonary moist rales. The infant was diagnosed with severe pneumonia and we immediately gave CPAP assisted ventilation (FiO2 50% PEEP 5 cmH2O). Meanwhile, we actively carried out blood culture, sputum culture, throat swab, respiratory virus (respiratory syncytial virus, influenza viruses, parainfluenza viruses, adenovirus, rhinovirus) and mycoplasma detection from blood and galactomannan detection. Then intravenous fluids and meropenem were administered (Figure 1). Chest X-ray showed high-density shadow in the left middle lobe lung on Day 1. But her general condition progressively worsened after 3 days. Her white blood cell count increased from 5.71 x 109/L (with 52% neutrophils and 27.5% lymphocytes) to 16.37 x 109/L (with 74.9% neutrophils and 16.7% lymphocytes), whereas her C-reactive protein and procalcitonin levels were normal. Pulmonary atelectasis in the right upper lobe and bilateral alveolar consolidation by chest computed tomography on Day 6 after the onset of symptoms (Figure 2A). Meanwhile repeated blood and sputum secretions were negative for bacteria, respiratory virus, tuberculosis, and fungi in cultures, and G-test (1,3 -beta-D-glucan test) and GM-test (galactomannan test), respectively. Her oxygenation index was 125 at admission, indicating a bad oxygenation status. And her echocardiography and blood pro-brain natriuretic peptide readings were normal. During this period, the infant showed polypnea, paroxysmal dysphoria, cough, and abundant yellow sticky respiratory secretions. Given the concern for a severe infection, empiric broad-spectrum antibiotics consisting of meropenem, vancomycin, and voriconazole to cover typical bacterial pathogens and fungal infection after a second infectious workup was performed including repeated blood culture, sputum culture (Figure 1).
At day 10, the microbial species were then assessed by metagenomic analysis. Deoxyribonucleic acid libraries for Next-generation sequencing (NGS) were prepared as previously described. Sequencing was performed on an Illumina MiSeq instrument. Total numbers of raw reads were 13849671, and non-human reads accounted for 5.92%. Stenotrophomonas maltophilia reads (428) were the only bacterial pathogen in blood (Figure 3A). In addition, we also detected several fungi pathogens in blood, including Penicillium chrysogenum reads (404), Pichia anomala reads (134), and Candida parapsilosis reads (Figures 3B-D). The infant was then treated with Tazobactam and Piperacillin (TZP) and trimethoprim/sulfamethoxazole (TMP-SMX) successively, subjected to non-invasive positive pressure ventilation. Her oxygenation status and chest computed tomography showed significant improvement after treatments (Figure 2B), and the infant was discharged on Day 30 after admission. Two weeks after discharge, the infant appeared good responses and appetite, and her chest computed tomography showed distribution of the two slightly thickened lung markings, clear lung fields and no substantive changes (Figure 2C).