A 62-year-old-male patient was referred to our emergency department on August 24, 2020, after experiencing a 28-day history of cough, expectoration and intermittent hemoptysis without fever. He just received treatment of relieving cough and reducing sputum from the outpatient clinic until his symptoms worsened and were accompanied by chills and fever (highest temperature 39.0  C) for 2 days and dyspnea for 1 day. He was diagnosed with pulmonary tuberculosis and was intensively treated with anti-tuberculosis drugs 10 years ago. He was never formally diagnosed with chronic obstructive lung disease despite a smoking history of about 20 pack-years. He was engaged in household waste recycling work but did not regularly wear a dust mask in the workplace.
On physical examination, he was tachypneic and had diffuse wet rales and low breath sounds in the right lung. His initial vital signs were 38.1  C of body temperature, 130 beats/min of heart rate, 26 breaths/min of respiration rate, and 92/60 mmHg of blood pressure (norepinephrine maintained intravenously with the speed of 0.1ug/kg/min). Laboratory examination showed a white blood cell count of 900/mm3, a neutrophil rate of 91.7%, platelet count of 17,000/mm3, a creatinine concentration of 154.0 mumol/L, a CRP concentration of 259.39 mg/L, a procalcitonin concentration of >100 ng/mL, immunoglobulin E of 56 kIU/L, a CD4+ lymphocyte count of 39/muL, and a CD8+ lymphocyte count of 20/muL. Arterial blood gas analysis showed pH 7.32, PaO2 59.6mmHg, PaCO2 29.7mmHg, HCO3- 15.4mmol/l, Lac 5.9 mmol/L, and oxygen saturation 92% (FiO2 60%). He had negative real-time reverse-transcriptase polymerase chain reaction results for coronavirus disease 2019 (COVID-19) and influenza A and B. Ziehl-Neelsen staining of the sputum was negative for acid-fast bacilli.
Then his hypoxia symptoms progressed rapidly and the intubation was performed. However, cardiac arrest occurred during tracheal intubation. Spontaneous circulation returned after cardiopulmonary resuscitation for 15 minutes but frequent episodes of paroxysmal ventricular tachycardia remained. Amiodarone was also performed. We excluded cardiac tamponade by emergency bedside echocardiography, acute coronary syndrome was not considered for lack of dynamically changed electrocardiogram and serum cardiac troponin I level. Oxygen saturation could be maintained by positive pressure ventilation (Tidal volume 450mL, Fraction of inspiration oxygen 60%, Positive end-expiratory pressure 12cmH2O, Respiratory rate 20/min). Computed tomography (CT) scan confirmed the presence of a thick-walled cavity in the posterior segment of the right upper lobe containing a 4.28cm*3.54cm soft tissue opacity attached to the cavity consistent with pulmonary aspergilloma and a mass of consolidation in the right lower lobe and patchy and nodule shadows in the left lower lobe (Figure 1A and B). Bronchiectasis and emphysema were also present. Bronchoscopic examination done under conscious sedation showed lots of sputum occluding the opening of the right airway bronchus. A biopsy of the right upper lobe B2 opening showed no cancer cells, though elevated serum squamous cell carcinoma-associated antigen level and enlarged mediastinal lymph nodes. Pulmonary aspergillosis and severe pneumonia were diagnosed. Caspofungin was empirically applied along with the antibiotic meropenem for decreased creatinine clearance of 43mL/min. Because of his acute kidney injury and anuria, continuous renal replacement therapy (CRRT) under regional citrate anticoagulation was also carried out. Subsequent serum BDG was 128.7 ng/L (0-100ng/L, Beijing Gold Mountainriver Tech Development Co. Ltd., China) and galactomannan (GM) was 0.05 (0-0.8, Bio-Rad Laboratories Shanghai Co., Ltd., China) on day 3. The aspergillus immunoglobulin G (IgG) levels was 172 AU/mL (0-35AU/mL). His sputum cultures also showed K. pneumoniae with a positive string test. Extended-spectrum beta-lactamase (ESBL) production was phenotypically confirmed using Clinical and Laboratory Standard Institute (CLSI) guidelines. The metagenomic next-generation sequencing (mNGS, performed by DIAN Diagnostics, China) of bronchoalveolar lavage fluid (BALF) revealed K. pneumoniae and A. flavus with reads of 3440 and 20, respectively. Meanwhile, the virulence genes iutA and rmpA2 as markers for hypervirulent pathotypes were present. The antimicrobial resistance gene SHV for ESBL was also detected. Antimicrobial susceptibility test showed that K. pneumoniae strains were susceptible to meropenem and piperacillin/tazobactam. Thus, invasive aspergillosis and hvKP coinfection were considered, the previous antibiotic treatment regimen was adopted unceasingly and clinical conditions gradually improved. The patient was weaned from CRRT on day 7 and from mechanical ventilation on day 10. Antimicrobials were also changed into piperacillin-tazobactam sodium (intravenously at 4.5g, q8h) on day 7 and voriconazole (orally at 0.2g, q12h) on day 10, whereas serum BDG and GM on day 10 rose to 231.3 ng/L and 5.50 respectively, then returned to normal until one month later. His BALF cultures on day 28 revealed A. flavus infection (Figure 2), whereas repeatedly negative of fungus before. The patient was discharged on day 48. Oral voriconazole therapy was continued for 1 year after discharge. Clinical symptoms and chest CT images gradually improved (Figure 1C-F). After more than one year of follow-up, the patient remained in good condition. The treatment process is shown in Figure 3.