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Introduction to hepatotoxicity caused by the beta-lactam family
Writing | Doraemon
Source | Clinical Pharmacy Channel
In this issue, let’s take a look at the hepatotoxicity caused by the other two major classes of β-lactams in the β-lactam family, cephalosporins and carbapenems. specialty.
Cephalosporins
The adverse reactions of cephalosporins and penicillins are similar to drug allergy and hypersensitivity reactions.
In general, cephalosporins have little to no hepatotoxicity, and only rare cases of liver injury from these drugs have been reported and vary from case to case.
The classic case of cephalosporin-induced liver injury is a form of self-limited cholestatic hepatitis with mild immunoallergic features 1-3 weeks after initiation of therapy, sometimes after a single Occurs after parenteral administration.
Ceftriaxone is a special case of cephalosporins, which, when administered parenterally, can cause cholestasis with symptoms of cholecystitis and cholestatic jaundice.
Therefore, with the exception of ceftriaxone, cephalosporins are often discussed as one broad class.
Cephalosporins other than ceftriaxone[1-2]
1. Hepatotoxicity
Slight increases in serum aminotransferase and alkaline phosphatase values can occur when cephalosporins are administered, but these are usually mild and transient.
Infrequent clinically significant liver injury is rare, only isolated case reports have been published, and not all preparations have been associated with cases of liver injury.
In typical cases, the incubation period is 1-4 weeks, and symptoms, usually including nausea, abdominal pain, itching, and jaundice, develop after antibiotics.
Cholestasis predominates with elevated serum enzymes, but mixed and hepatocellular cases have been reported. Liver injury is often accompanied by fever, rash, and eosinophilia or other allergic signs and symptoms.
The disease course is usually self-limiting and mortality is low.
2. Likelihood Score
B (Cefazolins are likely to be a rare cause of clinically apparent liver injury, mainly associated with the most commonly used drugs, eg, cefazolin, cephalexin).
3. Results and Management
In most case reports, recovery is rapid within 4 to 8 weeks, and it is unclear whether there is cross-sensitivity to cephalosporin-induced liver injury.
In many published cases, switching to another cephalosporin did not cause reinjury, but switching to another class of drugs other than cephalosporins is still recommended.
Similarly, patients with a history of penicillin allergy have a higher rate of hypersensitivity reactions to cephalosporins and should be avoided or used under careful monitoring.
Ceftriaxone[3]
1. Hepatotoxicity
Parentally administered ceftriaxone has been associated with silt-like stones in approximately 3% to 46% of patients.
Children may have a higher incidence than adults and are associated with higher doses and longer courses of treatment and possibly with fasting or dehydration.
This syndrome is called “pseudolithiasis”. The main component of the stone is ceftriaxone calcium. symptom.
Usually, serum enzyme and bilirubin levels remain normal even with biliary colic, but in rare cases, severe cholestatic jaundice or Gallstone pancreatitis requiring surgical intervention.
Sludge in the gallbladder and symptoms of gallbladder disease may appear within a few days of starting treatment, usually resolve rapidly when ceftriaxone is stopped, and can be detected by ultrasound within a few months Cases of biliary sludge and gallstones.
Ceftriaxone can also cause immunoallergic cholestatic hepatitis, a presentation consistent with, but very rare, described with other cephalosporins.
Symptoms of abdominal pain, nausea, itching, and jaundice appear within 1-4 weeks of starting treatment and may worsen 1-2 weeks after antibiotics are discontinued.
Elevated serum enzymes are mainly cholestasis, and the common clinical symptoms are fever, rash, and immunoallergic features of eosinophilia. Injuries are usually mild and self-limiting.
2. Likelihood Score
B (Ceftriaxone is likely the cause of clinically apparent liver injury, and may also cause ceftriaxone calcium in the gallbladder or biliary tree, bile sludge due to crystallisation in bile and ” Pseudolithiasis”).
3. Results and Management
In most case reports, recovery is rapid within 1-2 weeks, but some patients require cholecystectomy during acute illness, and stones or sludge may persistcontinued for several months.
The immunoallergic form of cholestatic hepatitis usually resolves rapidly and is not associated with acute liver failure or chronic injury.
Carbapenems—
Imipenem, Meropenem[4-5]
Most carbapenems have been reported to cause transient, mild-to-moderate, and asymptomatic increases in serum aminotransferase levels, although such elevations persist once treatment is discontinued fades quickly.
In addition, cholestatic liver injury has rarely been reported during, or shortly after, carbapenem therapy, and typically occurs in patients with a variety of other medical problems and other liver diseases in patients with the cause (parenteral nutrition, sepsis).
Carbapenems are mainly excreted unchanged in the urine and are rarely metabolized by the liver, so severe hepatotoxicity is rare.
1. Hepatotoxicity
In large clinical trials, approximately 6% of patients experienced transient and asymptomatic increases in serum aminotransferase levels 5-14 days after imipenem.
However, it is generally asymptomatic and no dose adjustment is required. Cholestatic jaundice has also been reported during or shortly after treatment, with an incubation period of 1-3 weeks, and the form of elevated serum enzymes is usually cholestatic.
Elevations of serum transaminases have been reported in 1%-6% of recipients after receiving intravenous meropenem for up to 14 days. These elevations are usually transient, mild, and asymptomatic and rarely require dose adjustment.
Meropenem has also been associated with a rare form of cholestatic jaundice, which usually occurs 1-3 weeks after treatment.
Carbapenems may exhibit immunoallergic features, but autoantibodies are rare. It has been reported that imipenem and meropenem cause vanishing bile duct syndrome, but no reports of acute liver failure caused by imipenem and meropenem have been reported.
2. Likelihood Score
Imipenem, Meropenem D (probable rare cause of clinically apparent liver injury).
3. Results and Management
Carbapenem-induced liver damage is usually mild and self-limiting. Cholestatic hepatitis, which can be caused by carbapenems, is also usually self-limiting and does not require treatment or intervention.
In patients with vanishing bile duct syndrome, corticosteroids are frequently used without shown benefit and are best avoided. Some patients may benefit from symptomatic treatment of pruritus associated with cholestasis with antihistamines, cholestyramine.
There is little information on the possible cross-sensitivity of different beta-lactam antibiotics to liver injury, but patients with clinically apparent liver injury from one carbapenem should avoid other carbapenems Penems.
Summary
Although the liver injury caused by beta-lactam antibiotics is greater Can not be ignored.
Clinic should standardize the use of antibiotics, strengthen the monitoring of patients’ liver and kidney function, and ensure drug safety.
References:
[1]LiverTox:Clinical and Research Information on Drug-Induced Liver Injury[Internet].Bethesda(MD):National Institute of Diabetes and Digestive and Kidney Diseases;2012-.Cephalosporins,Oral .[Updated 2021 Dec 20].
Available from: https:https://www.ncbi.nlm.nih.gov/books/NBK548358/
[2]LiverTox:Clinical and Research Information on Drug-Induced Liver Injury[Internet].Bethesda(MD):National Institute of Diabetes and Digestive and Kidney Diseases;2012-.Cephalosporins,Parenteral .[Updated 2021 Dec 20].
Available from: https:https://www.ncbi.nlm.nih.gov/books/NBK547862/
[3]LiverTox:Clinical and Research Information on Drug-Induced Liver Injury[Internet].Bethesda(MD):National Institute of Diabetes and Digestive and Kidney Diseases;2012-.Ceftriaxone.[ Updated 2021 Dec 20].
Available from: https:https://www.ncbi.nlm.nih.gov/books/NBK548258/
[4]LiverTox:Clinical and Research Information on Drug-Induced Liver Injury[Internet].Bethesda(MD):National Institute of Diabetes and Digestive and Kidney Diseases;2012-.Imipenem-Cilastatin.[Updated 2017 Jan 17].
Available from: https:https://www.ncbi.nlm.nih.gov/books/NBK548708/
[5]LiverTox:Clinical and Research Information on Drug-Induced Liver Injury[Internet].Bethesda(MD):National Institute of Diabetes and Digestive and Kidney Diseases;2012-.Meropenem.[ Updated 2017 Jan 17].
Available from: https:https://www.ncbi.nlm.nih.gov/books/NBK547861/
Source: Clinical Pharmacy Channel
Author: Doraemon
Editor in charge: Tian Dongliang
Proofreading: Zang Hengjia
Plate making: Xue Jiao