Page 84 - JCTR-11-1

Journal of Clinical and
Translational Research Meropenem-induced cholestasis

with meropenem therapy. The spectrum of liver injuries findings showed abnormal liver function tests, with
ranges from mild transaminase elevations to severe elevated aspartate aminotransferase (300 U/L [normal:
cholestasis, hepatic failure, and, in extreme cases, death. <40 U/L]), alanine aminotransferase (ALT; 280 U/L
3
Cholestasis, characterized by impaired bile flow, can [normal: <40 U/L]), total bilirubin (4.5 mg/dL [normal:
manifest as jaundice, pruritus, and elevated liver enzymes, <1.2 mg/dL]), (ALP; 250 U/L [normal: <120 U/L]),
particularly alkaline phosphatase (ALP) and bilirubin. along with a serum creatinine of 1.2 mg/dL (baseline).
The pathophysiology of meropenem-induced cholestasis Abdominal ultrasound showed no biliary obstruction
remains poorly understood, with proposed mechanisms and a normal-sized liver. The differential diagnosis
including direct hepatocellular toxicity, idiosyncratic included acute viral hepatitis, drug-induced liver injury,
reactions, and hypersensitivity. In addition, genetic pre- and autoimmune hepatitis. Laboratory investigations for
disposition, underlying liver disease, and concomitant use hepatitis B virus, hepatitis C virus, acute cytomegalovirus
of other hepatotoxic medications may increase the risk. 3 infection, Epstein-Barr virus, and herpes simplex virus
were negative. Given the temporal association between
In the context of rising antibiotic resistance and the
continued reliance on broad-spectrum agents such as meropenem administration and symptom onset, along
meropenem, recognizing and managing potential drug- with the exclusion of other potential causes, a diagnosis of
meropenem-induced cholestasis was established.
4
induced liver injury is critical. Timely identification
and discontinuation of the offending agent can prevent Meropenam was discontinued immediately on day 5.
further liver damage and improve clinical outcomes. This The patient was managed with antihistamines for pruritus
case report presents a detailed account of a patient who and monitored closely for liver function recovery. Liver
developed cholestasis following meropenem therapy, function tests were repeated weekly. One week after
emphasizing the importance of liver function monitoring discontinuation of meropenem, liver enzymes began
in patients receiving this antibiotic. By raising awareness to decline (Table 1). The patient reported resolution of
nd
of this potential adverse effect, we aim to enhance clinical pruritus and jaundice by the 2 week. For her ongoing
vigilance and improve patient safety in antibiotic therapy. infection, ceftriaxone was initiated as an alternative
antibiotic.
2. Case presentation
The pharmacovigilance assessment classified the
A 57-year-old female with a history of recurrent urinary reaction as “moderate” according to the Hartwig-Seigel
tract infections, hypertension, and mild chronic kidney scale. Preventability assessment using the Schumock-
5
disease was admitted with a diagnosis of pyelonephritis. Thornton scale categorized the reaction as “not
6
The patient reported a fever of 38.9°C and severe right- preventable.” The pattern of liver injury was determined
sided flank pain, rated 8/10 in intensity, exacerbated by based on the R-value, calculated as the ratio of ALT/
movement. She also experienced dysuria, characterized upper limit of normal (ULN): ALP/ULN. An R-value of
by a burning sensation. Mild nausea was noted, but there ≥5 indicates hepatocellular injury, ≤2 indicates cholestatic
was no vomiting or diarrhea. Her medication history injury, and values ranging 2 – 5 indicate mixed-type injury.
included lisinopril, metformin, and prior treatment with In this case, the calculated R-value was 3.36, suggesting
nitrofurantoin. There was no recent history of hypotension, mixed-type injury.
shock, or ischemia. Causality was further assessed using the updated
On admission, meropenem 1 g IV every 8 h was Roussel Uclaf Causality Assessment Method (RUCAM),
7
initiated. On day 4 of therapy, she developed pruritus and a validated tool for assessing drug-induced liver injury.
noticed yellowing of her skin and eyes. Clinical and physical The total RUCAM score was 9, grading the case as “highly
examination revealed stable vital signs, mild jaundice, and probable.” (Table 2) The case was subsequently reported to
no abdominal tenderness or signs of ascites. Laboratory the national pharmacovigilance program.

Table 1. Temporal trends in liver function and clinical markers
Days of therapy AST (U/L) ALT (U/L) Total bilirubin (mg/dL) Alkaline phosphatase (U/L) Creatinine (mg/dL)
Day 0 27 24 0.4 80 1.1
Day 4 300 280 4.5 250 1.2
Day 11 150 120 2.0 163 1.2
Day 18 50 45 1.0 110 1.0
Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.

Volume 11 Issue 1 (2025) 78 doi: 10.36922/jctr.24.00072