Global study provides practical guidance on antibiotic dosing for people with obesity

Key Takeaways: 

• A major systematic review has revealed how obesity alters the distribution and efficacy of antibiotics, with significant implications for dosing and therapeutic outcomes.
• While certain antibiotics such as β-lactams may not require routine adjustments, classes like aminoglycosides and glycopeptides require close monitoring and individualised dosing.
• The research team calls for global data sharing and improved pharmacokinetic studies to inform evidence-based dosing guidelines.
  

Introduction: A Call for Precision in Dosing

A large international team of researchers has published the most comprehensive analysis to date on antibiotic dosing in people living with obesity. Led by Dr Anne-Grete Märtson of Leiden University and Dr Thomas Tängdén of Uppsala University, the review brings together findings from 128 studies and proposes practical recommendations for clinical dosing adjustments. The work, published in The Lancet Infectious Diseases on 15 May, represents a significant step towards individualised antibiotic therapy in a population often overlooked in clinical pharmacology.

“It’s high time researchers started sharing more data,” said Märtson, underscoring the pressing need for greater collaboration to close longstanding gaps in clinical guidance.

Clinical Foundations and Rising Challenges

Märtson’s interest in the topic was informed by her early career as a clinical pharmacist in Estonia, where she participated in hospital ward rounds and focused on drug safety and dosing. “As a clinical pharmacist, I focused on the medication: was a certain combination of drugs safe, what was the optimal dose?”

Today, with rising obesity rates globally, clinicians are increasingly encountering challenges in treating infections effectively. “We’re increasingly seeing limited responses to administered medicines – in some patients the infection even worsens,” she noted. Complicating matters, most drug labels do not include dosing guidance for people with obesity, leaving clinicians without clear direction.

How Obesity Affects Antibiotic Pharmacokinetics

The review explains that obesity can significantly influence how antibiotics are absorbed, distributed, and cleared from the body. Changes in body composition, such as increased fat and muscle mass, and potential organ dysfunction, especially of the liver or kidneys, can affect the volume of distribution and drug metabolism.

“Substantial changes can occur in the volume of distribution due to increased fat and muscle mass, and tissue drug concentrations might be lowered,” the authors write.

Mahyar Etminan, a drug safety epidemiologist with EpiLytics Consulting who was not involved in the study, commented that “you need more of the drug to get into the tissue and that usually means higher doses than what we usually use in non-obese patients.” He also advised choosing antibiotics with higher tissue penetration.

128 Studies Analysed Across Multiple Drug Classes

Märtson and her colleagues systematically reviewed over 6,000 studies, narrowing their analysis to 128 that met strict inclusion criteria. Of these, 57 focused on β-lactam antibiotics, while 45 examined glycopeptides, lipoglycopeptides, and oxazolidinones. The analysis covered individuals aged 18 years and older with a Body Mass Index (BMI) over 30.

The findings showed that commonly prescribed antibiotics for pneumonia, urinary tract infections, and other bacterial conditions behave differently in people with obesity. “They distribute differently across the body’s tissues. Sometimes too little reaches the lungs, even though you’re trying to treat a lung infection,” Märtson explained.

Recommendations by Antibiotic Class

The review provides tailored guidance for specific classes of antibiotics:

β-lactams

This broad class, which includes penicillins and cephalosporins, is widely used for acute infections. Although obesity modestly alters their pharmacokinetics, the review concludes:

“Obesity modestly alters the pharmacokinetics of β-lactam antibiotics, but evidence does not support routine dose adjustments.”

However, it cautions against overly aggressive dosing due to the risk of toxic concentrations and side effects.

Aminoglycosides and Glycopeptides

These antibiotics are used for severe infections and require careful dose management.

“Therapeutic drug monitoring and the monitoring of creatinine clearance are highly recommended to guide maintenance dosing,” the authors state.

For aminoglycosides in particular, standard practice already includes therapeutic drug monitoring due to risks of nephrotoxicity and irreversible hearing damage. Dosing based on adjusted body weight is recommended to avoid under- or overdosing.

Other Antibiotic Classes

The study found that not all antibiotics require specific adjustments. In some cases, the pharmacological properties of the drug mean standard doses may remain appropriate, though further studies are needed to confirm this across more antibiotic types.

Optimising Dosing in Critical Care Settings

Märtson highlighted practical clinical strategies such as modifying infusion duration. “In critically ill patients, it can be helpful to administer the dose over two to four hours instead of half an hour via infusion,” she noted, emphasising the need to maintain appropriate plasma concentrations for effective treatment.

Gaps in the Data and the Need for Shared Research

Despite these insights, the researchers emphasise that much of the existing evidence remains limited. Many included studies were small-scale, and more robust pharmacokinetic data are needed. “There are excellent methods available to conduct high-quality research into this issue,” said Märtson, referencing tools like CT imaging to assess body composition and predictive modelling using large datasets.

The authors stress that:

“In the absence of robust pharmacokinetic data to inform dose adjustments, therapeutic drug monitoring can be useful to guide individualised dosing.”

They also call on future research to account for variables such as infection site, severity of illness, pathogen susceptibility, and potential drug toxicity when considering dosage in people with obesity.

Conclusion: Towards Evidence-Based Personalised Antibiotic Dosing

Märtson, Tängdén, and their multinational team – including contributors from the United States, Belgium, Austria, Germany, and Australia – have laid a critical foundation for improving antibiotic treatment in people with obesity. Their systematic review offers both immediate clinical value and a roadmap for future research.

As Märtson concluded, “I hope researchers will start sharing more data, so we can ultimately establish proper guidelines for all antibiotics.”