Case1
A six-month girl with congenital biliary atresia underwent liver transplantation. Engraftment on day 28 posttransplant was complicated by an increased alanine aminotransferase (ALT) level. She had no fever, cough and other symptoms while at home. She was suspected for rejecting the liver and admitted to hospital. On admission, her immunosuppression included tacrolimus (1.2 mg every 12 h)and methylprednisolone (12 mg every day).Her abnormal laboratory results included an ALT level of 283 U/L (normal: 7–40 U/L) and an aspartate aminotransferase (AST) level of 112.7 U/L (normal: 13–35 U/L). Empiric intravenous therapy with high-dose methylprednisolone( 80 mg intravenously every day) was initiated, along with oral tacrolimus continuously (1.2 mg every 12 h).Her ALT and AST were decreased gradually during hospitalization.
On the 25th hospital day, she presented with fever, cough with whitish sputum, and shortness of breath. Coarse crackles were heard over both lung fields. Laboratory data revealed a white blood cell(WBC) count of 25.45 × 109/L with neutrophil predominance (79%)(normal: 4–10 × 109/L), C-reactive protein(CRP) 51.26 mg/dl (normal: 0-3.5 U/L)and procalcitonin(PCT) 0.22 ng/mL(normal: 0-0.1 U/L). Computed tomography scan of the chest showed patchy infiltrations were seen in the upper lobe of right lung and lower lobe of left lung (Fig. 1, A). After the culture of blood and sputum, empiric antibiotics with meropenem (80 mg every 8 h), micafunginand (30 mg every day) and vancomycin (160 mg every 12 h) were administered for 6 days. Pathogenic serological and antibody-based assays, blood culture and respiratory culture were negative.
On the 31th admission, the patient needed mechanic ventilation because of worsening dyspnea. She was transferred to PICU. Her vital signs on arrival to PICU were as follows: blood pressure of 80/33 mmHg (mean arterial pressure of 48.7 mmHg), a respiratory rate of 50 breaths/minute, a heart rate of 240 beats/minute, a temperature of 38.3℃, and an oxygen saturation by pulse oximetry of 85% while breathing ambient air. Physical examination revealed with rales on auscultation, low skin temperature of limbs and capillary refill time 3 seconds. After a critical care medicine evaluation was requested, the patient was diagnosed by severe sepsis with septic shock likely resulting from HAP. Aggressive intravenous fluids resuscitation and vasopressors (norepinephrine, vasopressin) were initiated on arrival to PICU, and the patient was subsequently intubated and placed on mechanical ventilation because of worsening tachypnea and increased FiO2 requirements. Meanwhile, she was treated with continuous renal replacement therapy (CRRT) to eliminate inflammatory factors for 2 days. Empiric antibiotics with meropenem (370 mg every 8 h), caspofungin (30 mg every day) and vancomycin (140 mg every 8 h) were continued to be administered, along with oral tacrolimus and methylprednisolone.
We sent samples of blood and sputum to BGI Group (Beijing, China) for mNGS. Though Serum antibody, blood culture and respiratory culture were negative, mNGS indicated L. pneumophila in blood and sputum. For blood, there was 1044 raw reads and 516 raw reads for sputum of L. pneumophila. Intravenous antibiotic therapy followed by azithromycin (80 mg every day) for 10 days. On day three of PICU admission, vasopressors were titrated off. Computed tomography scan of the chest disclosed decreased infiltrations over the both lung (Fig. 1, B). The patient was extubated on the 5th day of PICU. Finally, after a 2-week stay in the PICU, her abnormal laboratory tests have returned to normal, and the patient recovered without any long-term sequelae.
Case2
A five-year-old boy with Burkitt lymphoma was in the end of early chemotherapy. He was presented with multiple ulcers in oral mucosa for 10 days. Abnormal laboratory tests showed a WBC count of 0.16 × 109/L with percentage of neutrophil 0.06%, hemoglobin 108 g/L (normal: 115–150 U/L) and a platelet count of 56 × 109/L(normal: 125–350 U/L). He was admitted to the hospital because of the diagnosis of myelosuppression (Ⅳ °) and ulcerative stomatitis. On admission, the patient was in the state of tracheotomy. The WBC and percentage of neutrophils decreased significantly, empiric antibiotics with meropenem (500 mg every 8 h), sulfamethoxazole (400 mg Q6H) and trimethoprim (80 mg Q6H) and vancomycin (330 mg every 8 h) were administered for 6 days.
On the 3th hospital day, the patient occurred fever, cough with yellow sputum at the tracheotomy. Widespread patchy infiltrations were seen in various segments of both lungs on computed tomography of the thorax (Fig. 2, C). On the 5th hospital day, the respiratory symptoms of the patient gradually worsening. He was transferred to PICU. His physical examinations at PICU admission included: blood pressure of 87/53 mmHg (mean arterial pressure of 61.0 mmHg), a respiratory rate of 40 breaths/minute, a heart rate of 160 beats/minute, a temperature of 36.3℃, multiple ulcers in oral mucosa, rales on auscultation, low skin temperature of limbs and capillary refill time 5 seconds. Laboratory findings showed a WBC count of 0.14 × 109/L with 0.21% neutrophil, hemoglobin 99 g/L and a platelet count of 39 × 109/L, CRP 281.36 mg/dl, PCT49.34 ng/mL and interleukin-6 (IL-6) 19259.97 pg/mL (normal: 1.7–16.6 pg/mL). Arterial blood gas (ABG)showed a pH of 7.408 (normal:7.35–7.45), a pCO2 level of 56.7 mmHg (normal: 35–45 mmHg), and a paO2 level of 33.10 mmHg (normal: 80–100 mmHg), Lactate 2.52 mmol/L (normal: 0–2 mmol/L). The patient was diagnosed by severe sepsis with septic shock likely resulting from HAP. Aggressive intravenous fluids resuscitation and vasopressors (norepinephrine, vasopressin) were initiated on arrival to PICU. And he was complicated by respiratory distress so that he required mechanic ventilation. He was treated with CRRT to eliminate IL6 for 6 days. On the 6th hospital day, the patient suddenly developed ventricular fibrillation with cyanosis and weak heart sound. An oxygen saturation by pulse oximetry of 88% while mechanic ventilation fall to 60%. Blood pressure fall to 60/40 mmHg.He was treated with cardiopulmonary resuscitation and intermittent intravenous injections of 1:10000 adrenaline. He recovered after 15 minutes. Serum antibody, blood culture and respiratory culture were negative.
We also sent samples of blood and sputum to BGI Group (Beijing, China) for mNGS. mNGS indicated Legionella pneumophila in blood and sputum. For blood, there was 2280 raw reads and 3372326 raw reads for sputum of L. pneumophila. He received Azithromycin (245 mg every day) therapy for 10 days. On the 12th hospital day, vasopressors were titrated off. On the 15th day of admission, chest radiography disclosed decreased infiltrations over the both lung (Fig. 2, D). And the patient was extubated. On the 28th hospital day, he was transferred to general ward because of stable vital signs and normal laboratory examination. He had no discomfort follow up 2 months.