A 24-year-old woman from the United States, weighing 70 kg and 175 cm, with no past history of interest, attended the emergency department with a dry cough, precordial discomfort, watery diarrhoea and fever. Examination revealed bilateral crackles and respiratory failure (baseline oxygen saturation 80%). Chest X-ray showed interstitial infiltrates and bilateral pneumothorax with pneumomediastinum. Laboratory tests showed leukocytosis with a left shift (11,700 - 109/L leukocytes, 81% neutrophils), CRP = 15.93 mg/mL and LDH = 1,154 IU/L. The following microbiological studies were performed, which were negative: two blood cultures, urine culture, antigenuria for Legionella and pneumococcus, pharyngeal swab for detection of Adenovirus, influenza A and B virus, parainfluenza virus, respiratory syncytial virus, Coronavirus, Rhinovirus and Enterovirus and blood sample for detection of HIV infection (anti-HIV antibodies and Ag p24). With suspicion of severe community-acquired pneumonia, empirical intravenous (IV) treatment was started with ceftriaxone 2 g/24 h, levofloxacin 500 mg/12 h for three days, continuing with 500 mg/24 h and oxygen therapy. The patient was admitted to the ICU.
In the first 48 hours the patient presented respiratory deterioration, requiring orotracheal intubation and mechanical ventilation, so on day +2 the IV antibiotic spectrum was extended to meropenem 1 g/6 h, linezolid 600 mg/12 h, liposomal amphotericin B 300 mg/24 h (to cover histoplasmosis) and acyclovir 750 mg/8 h. The patient's diarrhoea was limited to diarrhoea, which was limited to 2 days. Diarrhoea was limited. Due to progressive deterioration, doxycycline 100 mg/12 h iv, and methylprednisolone 60 mg/8 h iv were added on day +6 (due to the possibility of organisative pneumonia or vasculitis). The patient presented haemodynamic deterioration and progressive IR attributed to septic shock and nephrotoxicity, with a 24 h urine CLcr of 9.4 mL/min (day +6), being 106.5 mL/min on admission (estimated with the Cockcroft-Gault formula from a serum creatinine of 0.9 mg/dL). The aetiological study was extended with the determination of autoantibodies to rule out an autoimmune renopulmonary syndrome (anti-neutrophil cytoplasm and anti-basal membrane antibodies were negative), determination of galactomannan antigen in blood (negative) and bronchoalveolar lavage (BAL), where new bacterial and fungal cultures were requested (negative) and detection of viral antigens, all negative except PCR for Adenovirus (result received on day +7). Given that this was the only microbiological isolation and given the plausibility of the aetiology, it was classified as Adenovirus pneumonia with secondary acute respiratory distress syndrome. The serotype was not identified. Due to the patient's acute IR and the negativity of other isolates, liposomal amphotericin B and acyclovir were discontinued, the remaining antibiotic treatment was adjusted (meropenem 1 g/12 h iv and levofloxacin 250 mg/48 h iv)6 , and treatment was started with ganciclovir 200 mg/24 h iv (adjusted for renal function), awaiting improvement in CLcr before starting cidofovir. Given the presence of oligoanuria, it was decided to start renal replacement support on day +11 in the form of HDFVVC due to haemodynamic instability (desired loss volume of 100-160 mL/h, blood flow = 160 mL/min, effluent flow = 2 L/h; acrylonitrile haemofilter with surface area = 0.9 m2) with the corresponding dose adjustment of antibiotic treatments (meropenem 500 mg/8 h iv and levofloxacin 250 mg/24 h iv)7.
Three days later, empirical treatment with doxycycline and linezolid was discontinued. After starting ganciclovir, lymphopenia, plateletopenia and progressive anaemia accompanied by intra-alveolar bleeding were observed, and haematotoxicity may have been enhanced by previous linezolid treatment. Therefore, treatment with cidofovir was considered, even though renal function had not improved. Given the contraindication of its use in severe renal failure and the lack of references to its use in CVIDH in the technical data sheet, a literature search was performed in Pubmed and Micromedex without finding any reference. It was finally decided, taking into account the patient's renal function and the nephrotoxic effect of cidofovir, to initiate therapy with a reduced dose according to the strategy of Brody et al. in patients undergoing high-flux haemodialysis, and to consider empirically for our patient a CLcr of 40-50 mL/min (0.57-0.71 mL/kg/min). Thus, after obtaining informed family consent, an induction dose of 2.5 mg/kg (175 mg) was administered weekly for 2 weeks and every 15 days thereafter7. At the time of initiation of treatment (day +13) the patient had a residual diuresis of 300 mL/day.
To prevent nephrotoxicity, the usual treatment (hydration and probenecid) was carried out. Throughout cidofovir treatment, the patient remained on haemodiafiltration and had no attributable adverse effects. On day +17, a positive blood culture for coagulase-negative Staphylococcus was found and treatment with vancomycin 1 g/24 h (CLcr 40 mL/min) was started. After three doses of treatment, plasma concentrations of this antibiotic were monitored, obtaining a minimum concentration of 13 mg/dL, in line with those expected with a CLcr of 40 mL/min, and so the same dosage was continued.
After four doses of cidofovir, the PCR for Adenovirus was negative in LBA on day + 27. A lung biopsy was then performed where no signs suggestive of viral infection were found, and antiviral treatment was suspended.
Despite the treatment given, the patient's evolution was unfavourable, with refractory respiratory failure secondary to acute respiratory distress syndrome requiring support with Extracorporeal Membrane Oxygenation (ECMO), without further microbiological isolations, and increasing fibrosis component in the lung parenchyma as observed by transbronchial biopsy. The patient finally died after 52 days of hospitalisation.