Severe Drug-Induced Liver Injury as an Adverse Drug Event of Antibiotics: A Case Report and Review of the Literature

Munz, Martin; Grummich, Hans; Birkmann, Josef; Wilhelm, Martin; Holzgrabe, Ulrike; Sörgel, Fritz

doi:10.1159/000480399

Cited by 5 publications

(2 citation statements)

References 26 publications

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“…There are several case reports of cefazolin-induced liver injury. 49,50) In addition, it is also reported that the number of DILI cases attributed to cefazolin is higher than that with other cephalosporins. 51,52) However, there are few studies with comparison between patients with liver injury who used cefazolin and patients without liver injury who used this drug (i.e., risk evaluation).…”

Section: Discussionmentioning

confidence: 99%

Signal Detection of Potential Hepatotoxic Drugs: Case-Control Study Using Both a Spontaneous Reporting System and Electronic Medical Records

Akimoto

Nagashima

Minagawa

et al. 2021

Biological & Pharmaceutical Bulletin

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Drug-induced liver injury (DILI) is a common adverse drug event. Spontaneous reporting systems such as the Japanese Adverse Event Report Database (JADER) have been used to evaluate the association between drugs and adverse drug events. However, the association of drugs with adverse drug events may be overestimated due to reporting biases. Therefore, it is important to objectively evaluate the association using liver function test values. The aim of the present study was to predict potential hepatotoxic drugs using real-world data including electronic medical records and the JADER database. A total of 70009 (2779 with DILI and 67230 without DILI) and 438515 (10235 with DILI and 428280 without DILI) Japanese adult patients were extracted from electronic medical records and the JADER database, respectively. Drugs with ≥100 DILI patients in both of the two databases were regarded as suspected drugs for DILI. We used multivariate logistic regression to evaluate the association between the suspected drugs and increased risk of DILI. Among the suspected drugs, broad-spectrum antibiotics such as meropenem, tazobactam/piperacillin and ceftriaxone were significantly associated with an increased risk of DILI, and meropenem had a greater risk of DILI in both of the two databases. Additionally, there were significant associations of mosapride and L-carbocisteine with increased risk of DILI. In addition to well-known associations between antibiotic drugs and DILI, mosapride and L-carbocisteine were found to be new potential signals of drugs causing hepatotoxicity. This study indicates potential hepatotoxic drugs that require further causality assessment.

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Section: Discussionmentioning

confidence: 99%

Signal Detection of Potential Hepatotoxic Drugs: Case-Control Study Using Both a Spontaneous Reporting System and Electronic Medical Records

Akimoto

Nagashima

Minagawa

et al. 2021

Biological & Pharmaceutical Bulletin

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“…α2M is synthesized in the liver, and production is decreased with hepatic impairment [14,18]. Many candidate drug substances are reported to induce hepatopathy [15][16][17]. Evaluation of the degree of inflammation using serum concentrations of α2M may therefore give inaccurate results when assessing candidate substances that induce hepatopathy.…”

mentioning

confidence: 99%

Correlation between synthesis of α2-macroglobulin as acute phase protein and degree of hepatopathy in rats

Ito

Kuribayashi

2019

Lab Anim Res

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The degree of hepatopathy affecting the synthesis of α 2-macroglobulin (α2M) as an acute phase protein in rats was investigated. Hepatopathy was induced in Sprague-Dawley rats by intravenous administration of galactosamine at a dose of 30 mg/kg for 7 days. Inflammation was induced by intramuscular injection of turpentine oil at a dose of 2 mL/kg. Blood was collected before turpentine oil injection and at 24, 48, 72 and 96 h after injection. Serum concentrations of α2M were measured by enzyme-linked immunosorbent assay. Mean values of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in rats administered galactosamine were significantly higher than in controls. Mean values of body weight and total protein were significantly lower than in controls. Serum concentrations of α2M in the galactosamine group were significantly lower than in controls. Kinetic parameters, area under the concentration-time curve (AUC 0-96) and maximum serum concentration (Cmax), were significantly lower than in controls. The cutoff value for detecting the effects on synthesis of α2M in liver was 46.9 mgˑh/mL. Seven rats (77.8%) were assessed for decreases in the synthesis of α2M due to hepatopathy. Two rats showed no influence on the synthesis of α2M, despite administration of galactosamine. AST and ALT in these two rats were ≤ 285 and ≤ 174 U/L, respectively. In conclusion, synthesis of α2M in rats is evidently suppressed in the severe stages of hepatopathy.

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Antibacterials/paracetamol

2017

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Severe Drug-Induced Liver Injury as an Adverse Drug Event of Antibiotics: A Case Report and Review of the Literature

Cited by 5 publications

References 26 publications

Signal Detection of Potential Hepatotoxic Drugs: Case-Control Study Using Both a Spontaneous Reporting System and Electronic Medical Records

Signal Detection of Potential Hepatotoxic Drugs: Case-Control Study Using Both a Spontaneous Reporting System and Electronic Medical Records

Correlation between synthesis of α2-macroglobulin as acute phase protein and degree of hepatopathy in rats

Antibacterials/paracetamol

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