Case Presentation: A 64-year-old male with a history of spinal cord injury complicated by quadriplegia, neurogenic bladder and bowel presented with an obstructed suprapubic foley catheter, severe localized pain over the suprapubic area, and a blood pressure of 84/56 on arrival. The patient was administered intravenous fluids and started on 4.5g of piperacillin/tazobactam every 8 hours via extended infusion due to a recurrent history of extended-spectrum beta lactamase (ESBL) producing organisms growing in prior urine cultures. Initial urine culture from the emergency department revealed ESBL Proteus mirabilis sensitive to only piperacillin/tazobactam and carbapenems. CT-abdomen/pelvis was negative for renal staghorn calculi. On the 4th day of piperacillin/tazobactam treatment for his complicated catheter associated urinary tract infection (CAUTI), the patient began having recurrent visual hallucinations. Additionally, his mentation acutely changed from normal to lacking orientation to place, time and situation on the 7th day of antibiotic therapy. His encephalopathy persisted despite negative repeat infectious workup, normal electrolytes, adequate pain control and daily bowel movements. Piperacillin/tazobactam was discontinued after completing a full 7-day course. Over the next 36 hours, the patient’s mentation improved back to baseline with complete resolution of his hallucinations. Of note, the patient endorsed similar hallucinations with prior piperacillin/tazobactam therapy.

Discussion: For physicians, residents, and medical students, encephalopathy is one of the most common, yet complex complaints encountered. The vast etiology ranges from organic intracranial pathologies, metabolic or infectious disturbances, retention of bowel or bladder contents as well as a multitude of drug-induced causes. After starting piperacillin/tazobactam, our patient acutely developed perception changes which progressed to disorientation. Interestingly, all his symptoms resolved shortly after discontinuing piperacillin/tazobactam. Although other beta-lactam antibiotics, such as cefepime, are now well known to cause neurotoxicity, the reports of piperacillin/tazobactam induced encephalopathy are rare. An initial case report of piperacillin derived encephalopathy dates historically to 1996.1 The onset of encephalopathy after piperacillin administration has been reported between 1.5 and 7 days.2,3 Predisposing factors include a median daily dosage of 8g/day and renal insufficiency leading to drug accumulation. Our patient’s calculated creatinine clearance severely over-estimated his renal function because of generalized sarcopenia secondary to over 15 years of quadriplegia, which was reflected in his baseline serum creatinine 0.6mg/dL. A postulated mechanism attributes the encephalopathy to alteration of gamma-aminobutyric acid (GABA) transmission due to the similarities between the beta-lactam structure of piperacillin and GABA.3,4 Once the medication is discontinued, improvement is typically observed within 48 hours.4

Conclusions: Encephalopathy is one of the most broad and challenging diagnoses to evaluate. After evaluating for more common precipitants, such as metabolic or infectious derangements, it is also important to thoroughly review the medications the patient is receiving.