Disulfiram-like Reaction Involving Ceftriaxone in a Pediatric Patient

Abstract

Several medications have been shown to cause disulfiram-like reactions in patients concomitantly exposed to ethanol, including specific cephalosporin antibiotics that possess a methylthiotetrazole substituent. Within the cephalosporin class, there are few reports of disulfiram-like reactions with ceftriaxone. This case report is the first to involve a pediatric patient, and it describes a mild but likely disulfiram-like reaction manifesting as facial flushing in an 8-year-old male upon receiving a ceftriaxone infusion preceded by a dose of prednisolone elixir (5% ethanol by volume) for presumed community-acquired pneumonia thought to be complicated by an asthma exacerbation. The patient's flushing resolved with intravenous diphenhydramine, did not reappear, and was diagnosed as an allergy to ceftriaxone. Upon further evaluation, a hypersensitivity reaction was considered unlikely, and the allergy history was revised. The patient's antibiotic treatment was switched to azithromycin without steroids, and he had no further issues. This case suggests there is benefit in increased monitoring of pediatric patients receiving certain cephalosporins along with alcohol-containing medications, and it demonstrates how disulfiram reactions can easily be misinterpreted as hypersensitivity reactions. Aside from just alcohol-cephalosporin interactions, this case underscores the need for general vigilance when using alcohol-containing drug preparations in pediatric patients in an effort to prevent adverse effects and potential drug interactions.

Fact versus Fiction: a Review of the Evidence behind Alcohol and Antibiotic Interactions

“…Cephalosporins with an MTT side chain or an MTDT ring have an increased risk of a disulfiram-like reaction (15)(16)(17)(18)(19)(20)(21)(22).…”

“…(iii) Toxicity/ADR. Several cephalosporins have been reported to cause disulfiramlike reactions, particularly those that possess a methylthiotetrazole (MTT) substituent (i.e., cefotetan, cefoperazone, cefamandole, cefmetazole) (15)(16)(17)(18)(19)(20)(21)(22). The MTT structure resembles part of the disulfiram molecule.…”

“…The MTT structure resembles part of the disulfiram molecule. Ceftriaxone, which is commonly given as outpatient parenteral therapy, possesses a related methylthiodioxotriazine (MTDT) ring instead of an MTT side chain but has also been reported to cause disulfiram-like reactions (18,19,21,22). The MTDT ring increases its elimination half-life and serum protein binding (19).…”

“…Ceftriaxone, which is commonly given as outpatient parenteral therapy, possesses a related methylthiodioxotriazine (MTDT) ring instead of an MTT side chain but has also been reported to cause disulfiram-like reactions (18,19,21,22). The MTDT ring increases its elimination half-life and serum protein binding (19). A retrospective review conducted in China evaluated 78 cephalosporin-induced disulfiram-like reactions where drug hypersensitivity reactions were excluded via cephalosporin skin testing prior to intravenous cephalosporin receipt (18).…”

Inactivation of Aldehyde Dehydrogenase by Disulfiram in the Presence and Absence of Lipoic Acid or Dihydrolipoic Acid: An in Vitro Study

“…Moreover, it should be remembered that, apart from DSF, many other drugs, i.e., antibiotics are implicated in inducing a DSF-like reaction [3,4,5]. Furthermore, DSF-like side effects can occur when EtOH is used together with some plant-derived pharmaceuticals or dietary supplements since they inhibit the activity of ALDH [6,7].…”