Piperacillin/tazobactam/vancomycin

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

A 46-year-old-man developed Clostridium difficile colitis following empirical antibiotic therapy with piperacillin/tazobactam and vancomycin [dosages not stated].

The man, whose medical history was significant for obstructive sleep apnoea, presented to hospital with diarrhoea and shortness of breath. He was diagnosed with COVID-19 pneumonia. Hence, he started receiving remdesivir and off-label methylprednisolone and convalescent-anti-SARS-CoV-2-plasma [convalescent plasma]. He also received IV piperacillin/tazobactam and IV vancomycin as empiric therapy for possible bacterial pneumonia. He was intubated and mechanically ventilated due to acute hypoxic respiratory failure on day 5, and was transferred to a higher centre. Blood cultures revealed no growth; hence, piperacillin/tazobactam and vancomycin were discontinued. Later, on day 7, his feeding tube was dislodged causing an aspiration event, which further resulted in septic shock, which necessitated vasopressor support. Additionally, IV piperacillin/tazobactam was resumed. Over the following 48 hours, he developed oliguria, profuse diarrhoea, with multiple laboratory abnormalities. A PCR test for C. difficile was found positive. Subsequent CT scan of the abdomen and pelvis revealed evidence of pancolitis.

Therefore, piperacillin/tazobactam was discontinued, and the man started receiving oral vancomycin with metronidazole. He also received continuous renal replacement therapy. Later, on day 11, his vasopressor requirements abruptly increased. Laboratory analyses indicated toxic megacolon with perforation. Hence, an emergency exploratory laparotomy was performed, with total abdominal colectomy. His abdomen was closed after repeat exploratory laparotomy and end ileostomy after 2 days. His clinical status acutely worsened overnight, with deteriorating metabolic acidosis. He developed hypothermia, while his haemoglobin levels dropped to 6.4 g/dL, which necessitated RBC transfusion. A CT scan of the abdomen/pelvis demonstrated haemoperitoneum. He underwent four more surgeries for the management of persistent haemorrhagic shock, which was additionally complicated with disseminated intravascular coagulation, which necessitated further resuscitation with blood products. Finally, on hospital day 17, he was found to have ST segment elevations. Electrocardiogram with serial troponins confirmed anterior-inferior wall ST elevation myocardial infarction. Following discussion with his family, he was transitioned to comfort care. He passed away a few hours later. The development of the Clostridium difficile colitis was thus attributed to the initial antibiotic therapy with piperacillin/tazobactam and vancomycin.