A 35-year-old male RTR (in March 2019) with high serological risk for CMV (donor IgG+/recipient IgG-) received induction immunosuppression based in basiliximab (BSL) and maintenance with tacrolimus (TAC) 0.10 mg/kg/day, mycophenolic acid (MMF) 1 g every 12 hours, and prednisone (PDN) 5 mg every 24 hours. The patient's prophylaxis treatment with valganciclovir (VGC) 900 mg/day for 6 months and the evolution of the transplant were satisfactory, with an average creatinine of 1.2 mg/dl and without events of acute rejection (AR). In January 2021, he presented with SARS-CoV-2 (RT-PCR +) and fever for 3 days (37.7-38 C), without oximetry alterations and with the following management: paracetamol per os (PO) in case of fever, ivermectin 6 mg PO every 12 hours for 3 days, azithromycin 500 mg PO every 24 hours for 3 days, melatonin 5 mg PO every 24 hours, zinc 50 mg PO every 12 hours, vitamin D 5000 IU PO every 24 hours, and famotidine 20 mg PO every 12 hours. In addition, the TAC dose was reduced by 50%, and the antimetabolite (MMF) was suspended. Prednisone was maintained at 5 mg per day, with the remission of symptoms.
In April 2021, the patient's fever returned (39 C), predominantly at night, and he experienced shivers, diaphoresis, diarrhea, unwellness, general hyporexia, dry cough, dyspnea, and weight loss, requiring hospitalization and initiation of the diagnostic work-up with RT-PCR for SARS-CoV-2 with negative results. A Chest X-ray (Figure 1) showed an extensive nodular pattern in both lung fields, and chest tomography (Figure 2) showed a predominantly central pattern of bilateral ground glass opacities.
Bronchoscopy with bronchoalveolar lavage was performed with the PCR result positive for Mycobacterium tuberculosis (MTb), RSV, and CMV. Management with antituberculosis medications was initiated (rifampin 600 mg, isoniazid 300 mg, pyrazinamide 1600 mg, and ethambutol 1200 mg every 24 hours; ganciclovir 5 mg/kg IV every 12 hours; and antibiotics adjusted to renal function (meropenem 1 g IV every 12 hours, levofloxacin 500 mg IV every 48 hours, and linezolid 600 mg IV every 12 hours)), and the immunosuppressants were suspended (TAC and MMF), continuing only with PDN 5 mg per day. The patient's evolution was unfavorable with progressive dyspnea, persistent fever, tachycardia (140 beats/minute), hypoaeration in both pulmonary fields, and oxygen saturation of 80% despite the use of high-flow nasal cannulas (FiO2 100%), as well as the need for mechanical ventilation (MVI) and the use of norepinephrine (average dose of 0.1 mcg/kg/min) for septic shock. The patient's biochemical characteristics on hospitalization and during evolution are shown in Table 1.
Seven days later, due to the lack of clinical response, empirical treatment with liposomal amphotericin B was initiated (0.14 mg/kg/d) with clinical improvements in the ventilatory parameters. The final report provided 10 days after the initiation of therapy with amphotericin B showed the growth of Histoplasma capsulatum in the cultivation medium of the bronchoalveolar lavage done 4 days after hospitalization (Figure 3).
However, the final evolution was deterioration of the respiratory pattern due to bacterial superinfection (Acinetobacter baumannii and Klebsiella pneumoniae) isolated through bronchoalveolar lavage obtained 5 days after MVI, with a multi-drug-resistant profile and sensitivity only to polymyxins and tigecycline at a minimum inhibitory concentration (MIC; mug/ml) < 2 and <=1, respectively. Therefore, the decision made by our medical team was to initiate colistin (polymyxin E) at a loading dose of 3.5 mg/kg/d and a maintenance dose of 2.5 mg/k/d, divided into two doses, and tigecycline at an initial dose of 100 mg and a maintenance of 50 mg every 12 hours. Nevertheless, the patient evolution was catastrophic, and the outcome was fatal.