Pancreatic adverse events in patients treated with immune checkpoint inhibitors.

Background and Aim: The inhibition of cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) has been a target for multiple drugs to enhance the T-cell antitumor activity. However, these immune checkpoint inhibitors (ICIs) come with a panel of immune-related adverse events (irAEs) that include mainly endocrine, skin, and gastrointestinal effects. We report seven cases of pancreatic irAEs in patients treated with ICIs at our institute. Methods: This is a case series; data was collected through chart review by 3 different data collectors and was analyzed separately by 2 physicians. Results: Of these seven cases, two had diabetic ketoacidosis (DKA), while five had pancreatitis diagnosed by a substantial rise in serum lipase. Pancreatitis was asymptomatic in two cases. A pancreatic biopsy in one case revealed type 2 autoimmune pancreatitis. The ICIs used included pembrolizumab, nivolumab, durvalumab, and avelumab. Treatment included steroids and holding the ICI therapy: three cases had complete resolution of pancreatitis while two cases required either a prolonged taper or a second course of prednisone for recurrence of pancreatitis. On the other hand, the DKA cases were treated with withdrawal of the ICI and starting insulin with no steroid therapy. Conclusions: Pancreatitis and DKA are rare adverse events of ICIs that can be controlled by holding the ICI with or without starting steroids. Rechallenging the patient with the same ICI is possible in selected cases.

Meropenem-Resistant Pandoraea Pneumonia in a Critically Ill Patient With COVID-19.

Among patients infected with respiratory viruses, primary coinfection or secondary bacterial pneumonia is common in the severely ill. Pandoraea are multi-drug resistant gram-negative bacilli that have been newly classified in the past 20 years. We present the first reported case of Pandoraea co-infection with SARS-CoV-2 infection. A critically ill gentleman with COVID-19 in acute respiratory distress syndrome (ARDS) requiring mechanical ventilation developed ventilator-associated bacterial pneumonia (VAP). Initial sputum cultures grew Pandoraea species, with subsequent cultures growing P. aeruginosa, and K. pneumoniae as well. The patient failed to improve despite several antibiotic regimens including meropenem. Send-out reference laboratory testing of the Pandoraea species showed susceptibility to amikacin, ciprofloxacin, levofloxacin, imipenem, and minocycline, but resistance to aztreonam, cefepime, ceftazidime, and meropenem. The patient had deteriorated to multi-organ failure by the time minocycline was initiated, and his family had transitioned him into hospice care. Carbapenems are vital agents in the treatment of VAP. Pandoraea species are often resistant to meropenem but often retain in-vitro sensitivity to imipenem-cilastin. Although mainly isolated from respiratory specimens of patients with cystic fibrosis, cases of infection in non-cystic fibrosis patients have been increasingly recognized. The presentation of this case aims to increase awareness of the high drug resistance of this rising species and reduce delays in treatment, especially in COVID-19 coinfection.