Identification and Characterization of Cefazolin-Induced Liver Injury

Abstract

Background &Aims Cephalosporin antibiotics are popular because they have a broad spectrum of activity and are generally well tolerated; cephalosporin-induced liver injury is considered to be rare. We describe a new syndrome associated with a single intravenous dose of cefazolin and the clinical features of cephalosporin-induced liver injury. Methods The drug-induced liver injury (DILI) network collected detailed clinical data on 1212 patients with DILI between 2004 and 2012. We analyzed data from 41 patients in whom cephalosporins were implicated as primary agents of liver disease; 33 were formally adjudicated as having cephalosporin-induced DILI. Results Nineteen patients developed clinically apparent DILI after a single intravenous dose of cefazolin. All patients developed self-limited liver injury 3–23 days after receiving cefazolin during surgery—often during a minor outpatient procedure. The latency period was 20 days. Clinical features included itching, jaundice, nausea, fever, and rash. We identified 14 more patients with DILI attributed to other cephalosporins (5 first-, 2 second-, 6 third-, and 1 fourth-generation agents). Although latency and injury patterns were similar for cefazolin and other cephalosporins, the other cephalosporins were associated with more severe courses of injury, including 2 deaths from liver failure. Conclusions DILI can develop following a single dose of cefazolin. It is characterized by a latency period of 1–3 weeks after exposure, marked cholestasis, and a self-limited moderate to severe clinical course. Other cephalosporins can cause a similar but more severe injury.

Amoxicillin–Clavulanate-Induced Liver Injury

“…Here, we have demonstrated that AC is the most common cause of idiosyncratic liver injury in the DILIN data set and that, like other penicillins and cephalosporins, it causes predominantly a cholestatic-type liver injury [5, 14]. In addition, DILI due to AC, unlike DILI due to other drugs, appears to preferentially afflict older men.…”

A prospective study of the incidence of drug‐induced liver injury by the modern volatile anaesthetics sevoflurane and desflurane

“…However, drug‐induced liver injury from cephalosporins is uncommon and characteristically manifests as a cholestatic pattern of abnormal liver biochemistry that occurs at least one week after the drug, not during the first few days post‐operatively . It should be noted that ceftriaxone differs from other cephalosporins, and has been associated with biliary sludge, cholecystitis and cholestatic jaundice …”

Drug-induced Liver Injury

“…Amoxicillin-clavulanate, typically given as a 10-day course, is associated with a cholestatic hepatitis that may not been seen for one to three weeks after the drug is stopped 16 . A single dose of cefazolin, given as antibacterial prophylaxis prior to surgery, is associated with cholestatic injury that manifests up to three weeks later 68 . Toxicological analysis may be helpful in the follow-up evaluation of DILI, but with the exception of tests for acetaminophen adducts, may not be available in real time.…”