Trimethoprim‐Sulfamethoxazole‐Induced Hepatotoxicity in a Pediatric Patient

Abstract

Due to the escalating rates of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection, trimethoprim-sulfamethoxazole (TMP-SMX) is being used increasingly in the pediatric population for skin and soft tissue infections. Although this combination agent has been associated with a hypersensitivity syndrome involving cutaneous skin eruptions, pediatric cases of TMP-SMX-induced hepatotoxicity are rare. We describe a relatively healthy, 9-year-old boy who developed a CA-MRSA skin and soft tissue infection and was treated with TMP-SMX. After 14 days of therapy, he was taken to the emergency department with a 3-day history of fever, headache, and neck pain. He was diagnosed with a viral syndrome, acetaminophen was prescribed, and he was sent home. Three days later, the patient returned to the emergency department with fever, vomiting, decreased energy and appetitie, and suprapubic abdominal pain, and he was hospitalized. Laboratory test results revealed elevated liver function test values. After other potential causes of liver toxicity were excluded, TMP-SMX was determined to be the cause of his acute liver toxicity. The drug was discontinued, his symptoms resolved, and his liver function tests returned to normal. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient's development of hepatotoxicity and the TMP-SMX therapy. This rare adverse reaction to TMP-SMX has been reported in adults; however, to our knowledge, it has been reported in only five other children. Due to the increasing use of TMP-SMX in children, clinicians should be aware of this potentially life-threatening, immunemediated hypersensitivity reaction. Fortunately, however, the hepatotoxicity appears to resolve after discontinuation of the TMP-SMX therapy in most reported cases. This case report illustrates the importance of early detection of drug-induced hepatotoxicity and timely drug discontinuation to prevent the need for liver transplantation.

Successful extracorporeal liver dialysis for the treatment of trimethoprim-sulfamethoxazole-induced fulminant hepatic failure

“…Although most patients with TMP-SMZ-induced fulminant hepatic failure improve with discontinuation of the drug, some may require resin haemoperfusion or liver transplantation. (1,5,7,8,12) Deaths from TMP-SMZ-induced fulminant hepatic failure have also been reported. (4,5) Table II summarises the reported cases of patients with TMP-SMZ-induced fulminant hepatic failure.…”

“…(4,5) Table II summarises the reported cases of patients with TMP-SMZ-induced fulminant hepatic failure. (1,4,5,7,13,14) In patients with suspected TMP-SMZ-induced hepatotoxicity, the offending drug should be discontinued immediately.…”

“…Besides that, TMP-SMZ also has an important role in the prophylaxis and treatment of Pneumocystis jiroveci pneumonia in immunocompromised patients. (1) TMP-SMZ-induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but recognised complication, occurring in 0.01%-0.1% of patients, (2) and can cause fulminant hepatic failure. We describe a case of TMP-SMZinduced DRESS syndrome associated with fulminant hepatic failure in an adolescent who was successfully managed with extracorporeal liver dialysis.…”

Hepatotoxicity Induced by Trimethoprim-Sulfamethoxazole in a Child with Cystic Fibrosis

“…relatively rare and, to our knowledge, was previously described only in children without CF. 5,6 TMP-SMX-associated liver hepatotoxicity has not been reported in children with CF. We describe a 14-year-old female child with CF who was given oral TMP-SMX for an acute pulmonary infectious exacerbation.…”

“…As a result, delayed ADR symptoms may be attributed to primary disease, comorbid conditions, or other medications. 5 Hepatic hypersensitivity secondary to TMP-SMX is Patients with cystic fibrosis (CF) have chronic and progressive lung infections with various bacterial organisms that require treatment with oral and intravenous antibiotics on a regular basis. Trimethoprim-sulfamethoxazole (TMP-SMX) is one of the medications used to treat acute pulmonary infectious exacerbations in patients with CF.…”