Which erythromycin causes hepatic problems




















To avoid inter-laboratory fluctuations, we use the differences between the final and initial ALT and CRP levels as indirect tools to document these plausible mechanisms, which could be the reason for the improvement in hepatic function obtained in other studies by the long term use of antibiotics and prokinetics in cirrhotic patients [ 10 ].

Not only SIBO must be discussed as an oligosymptomatic cause of HE, but other bacterial infections in cirrhotic patients might be important, as Helicobacter pylori infection. In this study, the subjects were not submitted to H. In contrast, neomycin is probably useless against bacterial infections in the stomach. Motility disturbances are clearly associated to cirrhosis, but the subjects evaluated in this study were not submitted to motility exams.

Some patients could have a better effect of erythromycin than others, and this information is important in view of future uses of erythromycin in patients with HE. According to the good results obtained with prokinetics in cirrhotic patients, erythromycin must be evaluated in other studies about this condition [ 10 — 12 ]. Hence, given that antibiotics are already considered the best options for HE treatment and that the new drugs are still not useful in clinical practice, our proposal is very attractive because erythromycin is well known, easy to administer and less expensive than other treatments [ 23 ].

We hope that new studies can confirm the security profile of this dosage in cirrhotic patients. In conclusion, the use of erythromycin in HE patients achieved reductions of both hospitalization length and ALT levels when compared to neomycin. Additionally, the length of hospitalization caused by HE was positively correlated with CRP levels measured before and during the antibiotic treatment.

There were no adverse events that could be related to the drugs utilized, even in patients with advanced liver disease, but the latter finding needs to be confirmed in future studies. Poordad FF: Review article: the burden of hepatic encephalopathy. Aliment Pharmacol Ther. Article PubMed Google Scholar. Ther Clin Risk Manag.

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Correspondence to Fernando Gomes Romeiro. FGR conducted the patients, performed the comparative analysis and drafted the final article. FSY conducted the patients enrolled. CAC participated in the comparative analysis and drafted the article. All authors read and approved the final manuscript. This article is published under license to BioMed Central Ltd.

Reprints and Permissions. Romeiro, F. Erythromycin versus neomycin in the treatment of hepatic encephalopathy in cirrhosis: a randomized double-blind study. BMC Gastroenterol 13, 13 Download citation. Received : 02 May Accepted : 12 January Published : 16 January Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.

Skip to main content. Search all BMC articles Search. Download PDF. Died from intracranial bleed as shown by head CT. Bleeding related to coagulopathy from acute liver failure. Rapidly expired from hemorrhagic shock from massive acute upper gastrointestinal bleeding, associated with profound coagulopathy.

Planned liver biopsy could not be performed because of profound coagulopathy see autopsy. Serum acetaminophen level of zero on admission. Rarely drank alcohol. No serologic testing for hepatitis E. Negative extensive workup for metabolic and infectious causes of liver disease.

Normal ERCP findings. No recent acetaminophen use. No prior alcoholism. Extensive list of chronically used medications before instituting clarithromycin therapy. Disulfiram implicated as a cofactor in liver injury; disulfiram is a cytochrome P enzyme inhibitor which may increase clarithromycin levels.

Recent trip to India. Social drinker of alcohol. Suffering from left-sided heart failure treated with atenolol. Also, receiving israpidine when developed liver failure. Extensive workup found no other metabolic or infectious causes of acute liver failure.

Took four times normal initial dose of clarithromycin. Taking antipsychotic medications. Liver histology at autopsy of limited value due to advanced autolysis because autopsy performed 40 days after death Taking several other drugs for various diseases, but all of these drugs were chronically taken without prior toxicity.

Extremely extensive workup found no other metabolic or infectious cause of acute liver failure. Table 2. Reported cases of fulminant liver failure associated with clarithromycin. References W. Lee, R. Stravitz, and A. Squires, S. Nyberg, E. Doo, and J.

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Future simulation work will incorporate mitochondrial biogenesis into DILIsym and compare the effects of this adaptive mechanism on the simulation results.

One limitation of this work is that the metabolites of the macrolides were not investigated for their potential toxic effects. The results suggest that it is unlikely that metabolites of solithromycin, clarithromycin, and erythromycin are contributing to the observed ALT elevations; the liver responses for these molecules were adequately explained by the effects of the parent compound. Furthermore, the simulations were conducted in a SimPops intended to represent normal healthy volunteers; the ALT elevations were almost all observed in individuals with some sort of bacterial infection.

It is unclear whether infected individuals demonstrate a different level of drug exposure for many of the macrolides, though elderly individuals and individuals with community-acquired bacterial pneumonia have been shown to have a higher plasma concentration of telithromycin than normal healthy volunteers Differences in exposure between healthy volunteers and infected individuals may help explain some of the observed telithromycin and azithromycin toxicity; a better understanding of the differences in exposure between infected and healthy individuals is necessary.

Uncertainty in the in vitro-in vivo extrapolation IVIVE process for the toxicity parameters is also a plausible reason for the lack of predictivity for telithromycin and azithromycin; if the estimate of intracellular:extracellular concentration ratio derived from the mass spectrometry assay is significantly different from that which occurs in vivo, for example, the toxicity parameter derivation may be affected as a result.

However, the magnitude of the assay uncertainty necessary for this effect to be able to explain the missed predictions of telithromycin and azithromycin is quite large, as suggested by dose escalation simulations conducted on both compounds data not shown.

As a result, we view this as a less likely contributor than alternative mechanisms, patient effects, or metabolite effects. In conclusion, DILIsym was used to contextualize novel in vitro experiments and assess the likelihood that five macrolide antibiotics cause serum ALT elevations by oxidative stress, mitochondrial toxicity, and bile acid accumulation. DILIsym found that solithromycin and clarithromycin ALT elevations can be primarily accounted for by mitochondrial ETC inhibition whereas erythromycin ALT elevations can be primarily accounted for by inhibition of bile acid transporters.

Bile acid transporter inhibition may also in part account for ALT elevations caused by telithromycin, but the model predictions were poor for both telithromycin and azithromycin. This may reflect effects of metabolites of these drugs or involvement of mechanisms not included in DILIsym. This research demonstrates that despite the fact that these five drugs are all in the same class, they are mechanistically distinct from one another concerning their hepatic adverse effects.

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