On September 8, 2021, a 79-year-old man was admitted to the respiratory medicine department with a complaint of 3 days duration of fever, chills, bloody sputum and dyspnea. He was a rural farmer and there was a flooding event because of a heavy rain in his hometown 7 days before the onset. 2 days after the heavy rain, the patient harvested the rice in the paddy field. The patient had been well until 3 days before admission, when a moderate fever, chills and a cough productive of bloody sputum developed. The patient received antibiotic treatment of levofloxacin in a simple clinic in his hometown two days after the onset, but got no improvement in fever. Moreover, the symptom of dyspnea was getting worse. After the first treatment at the local clinic, the patient was hospitalized in the respiratory department of our hospital. The patient reported no history of headache or myalgia and denied having hypertension, diabetes, arrhythmia, coronary heart disease and tumor, which is consistent with blood pressure, laboratory findings, electrocardiogram (ECG, Fig. 1), cardiac ultrasound (Supplementary Fig. 1), abdominal ultrasound (Supplementary Fig. 2), thorax-CT (Supplementary Fig. 3A1-A3) and head CT (Fig. 2A1-A2) during hospitalization.
After 1 day of hospitalization in the respiratory department, the patient was referred to the intensive care unit (ICU) because of severe community acquired pneumonia with respiratory failure. On arrival at the ICU, the patient was very sick and drowsy. The patient presented tachycardia 135 beats per minute, body temperature 36℃, shortness of breath 35 times per minute, blood pressure 82/47mmHg, and oxygen saturation 75% while breathing ambient air. Jaundice was observed. Moist rales could be heard in both lungs. The extremities were cold, and the mottling score was 3. The superficial lymph nodes were not palpable. There was no gastrocnemius tenderness. The remainder of the examination was normal. The arterial blood gas analysis showed the following values: potential of hydrogen (PH) 7.44, partial pressure of carbon dioxide (PCO2) 24.6 mmHg, partial pressure of oxygen (PO2) 37 mmHg(fraction of inspiration O2 45%), actual bicarbonate radical (HCO3) -16.7 mmol/L, base excess (BE) -6 mmol/L, lactic acid (Lac) 3.8 mmol/L. The initial laboratory test revealed leukocytosis with white blood cell (WBC) 19.98 × 109/L, neutrophils accounting for 89.5%, thrombocytopenia with 72 × 109 platelets/L, hypersensitive C-reactive protein (hs-CRP): 199.66 mg/L, procalcitonin (PCT): 99.572 ng/ml, serum creatinine(Scr): 150.00 umol/L, total bilirubin (TBI): 63.60 umol/L, direct bilirubin (DBI): 43.50 umol/L, and Alanine aminotransferase (ALT) and glutamic oxalacetic transaminase (AST) at 30.20 IU/L and 76.80 IU/L, respectively. An emergency chest high resolution computed tomography (HRCT) scan was performed, and the results revealed both lungs had patchy ground glass opacity (GGO), a finding suggestive of pneumonia (Fig. 1A1-A3).
Accordingly, the primary diagnosis was made as follows: (1) severe community acquired pneumonia, (2) septic shock, (3) acute respiratory distress syndrome, and 4)multiple organ dysfunction syndrome. The patient received treatment with tracheal intubation, invasive mechanical ventilation and fluid resuscitation(sodium lactate ringer’s injection, 30ml / kg for 2 hours [12]). Intravenous antibiotics (levofloxacin, 500 mg, q.d.; Imipenem/Cilastatin Sodium, 1,000 mg, t.i.d.) were administered empirically. The fever gradually eased and the oxygen saturation improved. The blood and sputum cultures for bacteria and fungi were sterile. On September 13, a head CT scan was obtained which appeared normal (Fig. 2A1-A2) and the second chest CT scan showed most of the pulmonary ground glass opacity absorbed (Supplementary Fig. 3B1-B3). The bedside bronchoscopy showed a little bloody mucous sputum in the bronchi. According to the patient’s clinical manifestation and laboratory test results, we highly suspected he must be infected by some unknown pathogenic microorganism. On the 5th day after admission, we employed next-generation sequencing technique to detect etiology in the bronchoalveolar lavage fluid. Leptospira interrogans deoxyribonucleic acid (DNA) sequences were identified by next-generation sequencing analysis two days later. Then, we sent his blood to local disease control and prevention center to verify the next-generation sequencing results and the results of serum antibody titre tested by microscopic agglutination test were as follows: Leptospirosis interrogans serogroup Mini serovar for 1,600 and Leptospirosis interrogans serogroup Hebdomadis serovar for 800. We found the patient presented with left upper and lower limb mobility disorder on September 15, and muscle strength was grade 0. A second head CT scan (Fig. 2B1-B2) was performed on September 16th, and the results showed cerebral atrophy and a low-density shadow in the right basal ganglia. Compared with the first head CT scan on September 13th (Fig. 2A1-A2), the low-density shadow in the right basal ganglia was a new lesion. Therefore, the final diagnosis was as follows: (1) leptospirosis, (2) septic shock, (3) acute respiratory distress syndrome, (4) multiple organ dysfunction syndrome, and (5) Cerebral infarct. The patient was treated with intravenous penicillin 0.4 mU, q8h on September 16th. 7 h after the first dosage of penicillin, the patient’s condition deteriorated, with an abrupt fever of 40℃ and oxygen saturation dropped to 82%. The patient was considered to have developed Herxheimer reaction and was immediately given sedatives and intravenous hydrocortisone. Thereafter, the patient experienced a period of decreasing body temperature and increasing oxygen saturation. Nevertheless, the patient’s condition deteriorated further, requiring continuous pumping of norepinephrine to maintain blood pressure. Two days later, the patient died due to sepsis-induced acute circulation failure.