Cleveland Clinic study highlights importance of timing in preventing antibiotic resistance

Study highlights importance of dosage timing for preventing antibiotic resistance: ©Wladimir1804 -stock.adobe.com

A study from Cleveland Clinic researchers finds that missing or delaying early doses of antibiotics may play a bigger role in developing drug-resistant infections than previously believed. The findings, published in Science Advances, use an evolutionary modeling approach known as a “fitness seascape” to simulate how bacterial resistance develops in response to real-world treatment patterns.

“With the rise of ‘superbugs,’ or antibiotic-resistant bacterial infections, the world is reaching a crisis point,” said Jacob Scott, MD, DPhil., the study’s senior author. “We’ve already seen from MRSA what can happen if a bacterium becomes antibiotic-resistant. We need to address the problem before it impacts our ability to use antibiotics in more routine aspects of medical care, like surgery or childbirth.”

Led by Scott and first author Eshan King, an MD/PhD student at Case Western Reserve University School of Medicine, the research team sought to improve models that guide recommended antibiotic dosing. Traditional models assume static drug levels, but King’s expanded “seascape” models factor in fluctuating concentrations of medication in the body over time—particularly the impact of dosage timing.

“Many models assume the environment around a diseased area doesn't change, but the environment of an infection is our own bodies. That’s never truly constant,” King said. “Our manuscript builds on previous work to account for changes in drug concentration over time within our bodies.”

The team simulated hundreds of virtual patients receiving both IV and oral antibiotics. They discovered that the timing of doses—especially the early ones—had a larger impact on resistance than whether the full course was completed. Laboratory experiments confirmed the simulation results.

“Bacteria that were appropriately treated early on but missed later doses did not develop resistance,” the authors wrote. “In contrast, the bacteria that missed early doses but were appropriately treated later evolved treatment resistance.”

“These results are shaping how I will counsel my patients,” King added. “I will emphasize that they really need to be on top of taking their antibiotics at the recommended time intervals, especially at the beginning.”

Progress and challenges in combating antibiotic resistance

Antibiotic resistance has become one of the most pressing public health threats worldwide. According to the Centers for Disease Control and Prevention, more than 2.8 million antibiotic-resistant infections occur in the U.S. each year, resulting in over 35,000 deaths. The growing ineffectiveness of traditional antibiotics threatens not only infection treatment but also surgeries, cancer therapies, and other interventions that rely on infection control.

In response, researchers and clinicians are advancing both diagnostic and therapeutic approaches. Rapid molecular diagnostics now allow providers to identify resistant organisms in hours rather than days, leading to quicker and more targeted treatment. Meanwhile, machine learning models are increasingly being used to predict resistance patterns based on local epidemiology and patient history.

The development of new antibiotics remains slow, but efforts like the AMR Action Fund—a $1 billion public-private partnership—are working to bring new drugs to market by 2030. Scientists are also investigating “antibiotic adjuvants,” compounds that can be combined with existing drugs to restore their effectiveness, and bacteriophage therapy, which uses viruses that infect bacteria as precision tools to kill resistant strains.

The Cleveland Clinic study adds a critical behavioral and timing-based insight into the fight: how patients take antibiotics can be as important as which antibiotic they take. The findings could eventually inform more personalized prescribing and public education efforts to curb resistance at its earliest stage.