Page 85 - JCTR-11-1

Journal of Clinical and
Translational Research Meropenem-induced cholestasis

Table 2. Updated Roussel Uclaf Causality Assessment Method (RUCAM) scoring for this case
Variables Case details Score
1. Time of onset
From the beginning of the drug <5 days +1
From the cessation of the drug ≤15 days +1
2. Course
Change in ALP between the peak value and ULN Decrease ≥50% within 180 days +2
3. Risk factors
Alcohol/Pregnancy Absent +0
Age Age of the patient ≥55 years +1
4. Concomitant drugs None or no information or concomitant drug with 0
incompatible time to onset
5. Exclusion of other causes: All causes in Group I and II were ruled out +2
Group I (7 causes):
• Acute viral hepatitis due to HAV (IgM anti‐HAV), or
• HBV (HBsAg and/or IgM anti‐HBc), or
• HCV (anti‑HCV and/or HCV RNA with appropriate clinical history)
• HEV (Anti‑HEV‑IgM, anti‑HEV‑IgG, HEV‑RNA)
• Biliary obstruction (Through imaging)
• Alcoholism (History of excessive intake and AST/ALT ≥2)
• Recent history of hypotension, shock, or ischemia (within 2 weeks of onset)
Group II (2 categories of causes):
• Complications of underlying disease (s) such as autoimmune hepatitis,
sepsis, chronic hepatitis B or C, primary biliary cirrhosis or sclerosing
cholangitis; or
• Clinical features or serologic and virologic tests indicating acute CMV, EBV,
or HSV.
6. Previous information on the hepatotoxicity of the drug: +2
Reaction labeled in the product characteristics
7. Response to re-administration: Not done 0
Total RUCAM score 9
Abbreviations: ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CMV: Cytomegalovirus;
EBV: Epstein-Barr virus; HAV: Hepatitis A virus; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HEV: Hepatitis E virus; HSV: Herpes simplex virus;
ULN: Upper limit normal.

3. Discussion to cholestasis following meropenem exposure, as variability
in hepatic enzyme activity can alter drug metabolism and
Meropenem is an important therapeutic option for increase the risk of hepatotoxicity. In some cases, an immune
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managing serious infections, particularly in hospitalized response may contribute to liver injury. The immune system
patients and those with multidrug-resistant organisms. may mistakenly target hepatocytes after drug exposure,
However, as illustrated in this case, meropenem can induce triggering inflammation and subsequent cholestasis. This
cholestasis, a potentially serious side effect that warrants immune response can be particularly pronounced in
increased awareness among healthcare providers.
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The exact mechanisms by which meropenem induces patients with underlying autoimmune conditions or those
on multiple medications. Patients receiving meropenem
cholestasis remain unclear, but several hypotheses exist.
Some studies suggest that certain antibiotics can directly often have complex medical histories and may be on
damage hepatocytes or cholangiocytes, leading to bile polypharmacy regimens, increasing the potential for drug-
drug interactions that affect liver function. For example,
duct obstruction or impaired bile formation. This can
result in a cholestatic pattern of liver injury, characterized non-steroidal anti-inflammatory drugs, other antibiotics,
by elevated ALP and bilirubin levels. Drug-induced liver or medications for chronic conditions may interact with
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injury is often idiosyncratic, meaning it is unpredictable meropenem, further increasing the risk of liver injury.
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and not necessarily dose-dependent. Genetic variations Early identification of cholestasis is critical, as
in drug metabolism may pre-dispose certain individuals prompt discontinuation of the offending agent can lead

Volume 11 Issue 1 (2025) 79 doi: 10.36922/jctr.24.00072