Why do some antibiotics damage the liver more than others? IIT Bombay study has answers

Why is liver damage from antibiotics a concern?

Drug-induced liver injury is one of the primary reasons medicines are withdrawn from the market or restricted after approval. The challenge is that liver injury is notoriously hard to predict. Many patients show no symptoms initially, while others take multiple medications, making it difficult to identify the real culprit. Even closely related drugs can behave very differently.

What did the IIT Bombay study investigate?

“Traditionally, people believed that a drug molecule’s harm to cells comes from how much it ruptures the cell membrane. Our results can change that view,” Professor Kumar said.

Which antibiotics were compared?

The study focussed on two powerful antibiotics used against serious bacterial infections such as hospital-acquired and ventilator-associated pneumonia — Teicoplanin, often linked to liver problems in clinical practice and Oritavancin, which is usually better tolerated. Both are chemically similar and kill bacteria in nearly the same way, yet their liver toxicity differs significantly.

Researchers tested how the two drugs behaved using advanced biophysical techniques: Dynamic Light Scattering (DLS) to measure particle size and aggregation, Cryo-Transmission Electron Microscopy (cryo-TEM), to visualise structural changes in membranes and computer-based molecular modelling, to track drug localization within membranes.

What did the researchers find?

Oritavancin disrupted membranes more strongly, causing them to clump together and fuse, visibly altering their structure. Teicoplanin, surprisingly, left membranes largely intact but remained stuck at the surface, interacting for long periods. This surface-level persistence proved more harmful.

In rat studies, animals treated with Teicoplanin showed elevated liver enzymes, inflammation, and tissue damage. Rats given Oritavancin had only mild effects: enzyme levels rose slightly, and tissue damage was minimal. “Teicoplanin is more harmful to the liver, even though it only slightly disrupts membrane structure. That is because it sticks to the membrane surface, changing the surface charge and how the outer lipid layer is packed and moves,” explained first author Akash Kumar Jha. Oritavancin buries itself deeper inside the membrane. Its disruptive effects are real but less likely to interfere directly with surface-level processes critical for cell function

Why does location matter more than disruption?

The study suggests that persistent stress at the membrane surface interferes with normal cellular communication and electrical properties. Over time, these subtle disturbances accumulate, leading to chronic liver injury.

“Our results shift the focus from how much damage to where and how long a drug interacts with the membrane, helping explain why some drugs harm the liver more than others,” Professor Kumar said.

Together, these findings suggest that toxicity is not simply about chemical potency but about biophysical positioning within the cell membrane.

What are implications for drug development?

“By applying this membrane-focused approach, we may uncover why some treatments cause unexpected side effects and use that knowledge to design gentler compounds that are less toxic to healthy cells. Because these tests are relatively fast and scalable, they could be added to standard safety checks during drug development,” said Jha.

What are Teicoplanin and Oritavancin used for?

Professor Kumar explained that Teicoplanin and Oritavancin are powerful antibiotics used to treat serious infections caused by gram-positive bacteria, a group of bacteria that can cause life-threatening illnesses such as severe pneumonia, bloodstream infections, heart infections (endocarditis), and deep skin or bone infections. These are not medicines for common colds or mild coughs; they are usually given in hospitals, often to critically ill patients.

Teicoplanin has been used for many years and is commonly prescribed when infections are caused by resistant bacteria such as MRSA (methicillin-resistant Staphylococcus aureus). It is generally effective, but doctors have observed that in some patients it can raise liver enzyme levels or cause liver inflammation.

Oritavancin is a newer, long-acting antibiotic from the same family. It works in a similar way, by attacking the protective outer wall of bacteria and killing them, but it can sometimes be given as a single dose because it stays in the body longer. Clinical experience suggests it is usually better tolerated by the liver compared to Teicoplanin.

“Although both drugs fight bacteria in nearly the same way and are chemically similar, research now suggests they interact differently with liver cell membranes. Teicoplanin tends to remain attached to the surface of liver cells for longer periods, which may trigger more stress and inflammation. Oritavancin, on the other hand, penetrates deeper into the membrane and appears to cause less long-term irritation,” said Professor Kumar.

How do these bacteria infect people?

Gram-positive bacteria are commonly found in the environment and even on our own skin and in our nose or throat. Most of the time, they live harmlessly without causing disease. Infection happens when these bacteria enter the body through a cut, wound, surgical site, breathing tubes or medical devices like catheters.

Professor Kumar said, “In hospitals, the risk is higher because patients may already be weak, on ventilators, or undergoing surgery. For example, bacteria can enter the bloodstream through an IV line, infect the lungs in patients on ventilators, or infect heart valves in vulnerable individuals.”

He further explained that people with low immunity, diabetes, kidney disease, or those in intensive care units are especially at risk. “In some cases, the bacteria are resistant to common antibiotics, which is why stronger drugs like Teicoplanin or Oritavancin are used,” he added.