piperacillin--tazobactam-drug-combination and Coma

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Cephalosporins; Clinical Trials as Topic; Coma; Critical Illness; Delirium; Drug Therapy, Combination; Humans; Piperacillin, Tazobactam Drug Combination

Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial.. To determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction.. The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022.. Patients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam.. The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days.. There were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, -1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]).. Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction.. ClinicalTrials.gov Identifier: NCT05094154.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Cefepime; Coma; Delirium; Drug Therapy, Combination; Female; Humans; Kidney; Male; Middle Aged; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Sepsis

A 24-year-old woman with quadriplegia was admitted with respiratory failure because of pneumonia. She was on multiple medications including diazepam, oxycodone, and amitriptyline, known to be associated with coma blisters, though she did not overdose on any of them. On hospital day 2, she developed multiple blisters on both sides of her right forearm and hand. Skin biopsy showed eccrine gland degeneration consistent with coma blisters. It was felt that hypoxemia from her pneumonia contributed to the development of these blisters, which occurred on both pressure and non-pressure bearing areas of the arm. Coma blisters are self-limited skin lesions that occur at sites of maximal pressure, mostly in the setting of drug overdose. However, coma blisters may occur with metabolic and neurological conditions resulting in coma.

Topics: Amitriptyline; Anti-Bacterial Agents; Blister; Coma; Diazepam; Drug Therapy, Combination; Female; Humans; Mianserin; Mirtazapine; Oxycodone; Oxygen; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Pneumonia, Aspiration; Quadriplegia; Respiratory Insufficiency; Treatment Outcome; Young Adult