Intermittent hemodialysis treatment in cefepime‐induced neurotoxicity: Case report, pharmacokinetic modeling, and review of the literature

Abstract

Cefepime is a broad-spectrum cephalosporin indicated for in-hospital treatment of severe infections. Acute neurotoxicity, an increasingly recognized adverse effect of this drug in an overdose, predominantly affects patients with reduced renal function. Although dialytic approaches have been advocated to treat this condition, their role in this indication remains unclear. We report the case of an 88-year-old female patient with impaired renal function who developed life-threatening neurologic symptoms during cefepime therapy. She was treated with two intermittent 3-hour high-flux, high-efficiency hemodialysis sessions. Serial pre-, post-, and peridialytic (pre- and postfilter) serum cefepime concentrations were measured. Pharmacokinetic modeling showed that this dialytic strategy allowed for serum cefepime concentrations to return to the estimated nontoxic range 15 hours earlier than would have been the case without an intervention. The patient made a full clinical recovery over the next 48 hours. We conclude that at least 1 session of intermittent hemodialysis may shorten the time to return to the nontoxic range in severe clinically patent intoxication. It should be considered early in its clinical course pending chemical confirmation, even in frail elderly patients. Careful dosage adjustment and a high index of suspicion are essential in this population.

Three-times-weekly, post-dialysis cefepime therapy in patients on maintenance hemodialysis: a retrospective study

“…Although this Austrian group did not report significant side effects in their patients, the relatively high cefepime trough plasma concentrations which they measured were initially of concern to us because severe neurological side effects have been described with high levels of several beta-lactam antibiotics including cefepime [ 20 – 22 ]. Recently, Lamoth et al reported that the probability of cefepime-associated neurological toxicity (i.e.…”

“…They propose prescribing a fixed post-dialysis dose of 2 g three-times-weekly, but it should be noted that this dosage was associated with relatively high mean residual cefepime serum concentrations, e.g. 23 ± 7 mg/l [ 18 ], that may be associated to an increased risk of neurotoxicity [ 20 – 22 ].…”

Cefepime-induced neurotoxicity

“…Hemodialysis rapidly removes cefepime from blood and CSF and hastens recovery, especially in life-threatening situations. There have been several reports of emergent hemodialysis with successful results [2,6,14,41,45,46,74,82].…”

“…normalities, some described as CIN with TW or GPD [3,15,17,22,24,43,49,[70][71][72][73][74][75][76], whereas others reported these as CIN with NCSE [4][5][6]13,14,16,18,20,21,42,45,[77][78][79][80][81][82][83][84], depending on the author's view. Some investigators proposed that encephalopathies with GPD or severe metabolic encephalopathies with continuous epileptiform EEG abnormality are not NCSE, and that a coma with continuous generalized epileptiform discharges (coma-GED) should be differentiated from NCSE proper [67,69].…”

“…Immediate clinical improvement occurred exceptionally in few cases [20,76,81]. Second, most patients recovered after discontinuation of cefepime alone; furthermore, rapid elimination of cefepime through hemodialysis markedly sped their recovery compared with anticonvulsant therapy, from 2 to 1 day [2,10,14,45,74,82]. Third, if EEG abnormalities in patients with CIN indicate true NCSE, anticonvulsant therapy hastens clinical improvement [43,76]; however, AED was not effective in the recovery of EEG and clinical symptoms [10].…”