Size matters when it comes to antibiotics. Obese patients may need customized doses of certain drugs

Obesity can have a distinct impact on the absorption, effectiveness and excretion of antibiotics, medications that have been in use for more than 80 years, but only now have consensus guidelines been proposed on prescribing the drugs for patients with substantial fat mass.

The new research arrives amid two major global health crises: In 2022, the World Health Organization declared that 43% of the global adult population is overweight, and an estimated 16% of adults are considered obese, some severely so. Also, in recent years, the WHO has stressed the need for more efficient use of antibiotics to preserve their usefulness as drug-resistant superbugs become an increasingly lethal threat.

Now, an international team of medical investigators reports that obesity can interfere with antibiotics, resulting in too much or too little drug exposure to treat infections. And because dosages that effectively work in normal weight individuals don’t seem to treat the obese, the research team has developed obesity-specific antibiotic dosing guidelines for certain classes of the drugs.

Writing in The Lancet Infectious Diseases, the team describes its research as an in-depth systematic review of the medical literature on dosing and antibiotics. Conclusions drawn from the research created the framework for the guidelines.

“Obesity can alter antibiotic pharmacokinetics due to physiological changes, such as body composition and organ dysfunction that result in increased or decreased drug exposures in plasma or at the site of infection,” writes lead author Dr. Anne-Grete Märtson, a pharmacological researcher at Leiden University in the Netherlands. Along with her colleagues, Märtson makes a powerful case for obesity-based antibiotic dosing guidelines.

Researchers used the standard definition of obesity, a BMI of 30 or higher, and underscored that “substantial changes can occur in the volume of [systemic antibiotic] distribution due to increased fat and muscle mass.” In other words, obesity can alter how antibiotics are absorbed, distributed and excreted from the body.

The team began its systematic investigation with a review of 6,113 studies on obesity and antibiotic dosing. After eliminating duplicate studies, the team narrowed that number to 128 studies from which conclusions in the study were drawn.

A pictorial chart in the study illustrated problems facing the obese when it comes to taking antibiotics: increased fat mass, impaired kidney and/or liver function. Of special concern in the liver is the dysfunction of cytochrome P450, the group of enzymes responsible for metabolizing drugs.

Märtson and her collaborators studied a number of antibiotic classes and how body weight affects the drugs’ metabolism. Drug classes analyzed in the study included β-lactams, aminoglycosides, glycopeptides, lipoglycopeptides, and quinolones, among others. Yet, not all antibiotics require special guidelines for the obese.

“Obesity modestly alters the pharmacokinetics of β-lactam antibiotics, so evidence does not support routine dose adjustments [because of body weight],” Märtson and colleagues emphasized in the study. “For aminoglycosides and glycopeptides, the impact of obesity on pharmacokinetics is evident and weight-based dosing is recommended.”

β-lactam antibiotics include such widely prescribed drugs as the penicillins, cephalosporins, carbapenems and monobactams. They are chemically characterized by a β-lactam ring in their chemical structure. The drugs are used against a wide range of bacterial infections, including Gram-positive and Gram-negative species. But there’s no need to treat obese patients differently when it comes to β-lactam medications.

Doctors, meanwhile, frequently turn to aminoglycosides to treat extremely serious infections, especially those caused by Gram-negative bacteria. Aminoglycosides include such medications as gentamicin, streptomycin, and neomycin. These drugs work by disrupting critical protein production activity inside the bacterial cell. The drugs enter bacteria and bind to the 30S ribosomal subunit, resulting in flawed protein synthesis and death of the pathogens.

Guidelines were recommended for the use of this class in the obese as well as for glycopeptide antibiotics, which include the highly potent cell-wall-disrupting drug vancomycin.

“Maintenance doses [of vancomycin] should be individualized and guided by therapeutic drug monitoring to increase the probability of achieving therapeutic yet non-toxic drug exposures,” Märtson and her collaborators wrote.

The team did not provide a guideline based on total body weight for the quinolones, the drug class that includes the fluoroquinolones. However, the team’s recommendations stressed special consideration for administering fluoroquinolones.

“Higher or more frequent dosing resulting in higher systemic exposure should be considered for patients with obesity and severe deep-seated infections to reach adequate tissue concentration,” the team asserted.

Data were sparse for other antibiotic classes and will require additional study, according to findings from the research.

Recommendations for dose adjustments were drafted by Märtson and Dr. Thomas Tängdén of Uppsala University in Uppsala, Sweden. They worked with a far-flung group of collaborators from around the world to create guidelines to be recognized globally.

Team members hailed from the United States, Belgium, Austria, Germany, and Australia. Scientists from major European study groups and global scientific societies also participated. Among them are the Pharmacokinetics and Pharmacodynamics of Anti-Infectives Study Group of the European Society of Microbiology and Infectious Diseases; the International Society of Anti-Infective Pharmacology, and the Society of Infectious Diseases Pharmacists.

“When making decisions on dosing in obesity, the severity of illness, site of infection, susceptibility of the pathogen, and potential toxicity of the antibiotics should be considered,” Märtson and colleagues concluded. “In the absence of robust pharmacokinetic data to inform dose adjustments, therapeutic drug monitoring can be useful to guide individualized dosing.”

© 2025 Science X Network

Obesity can have a distinct impact on the absorption, effectiveness and excretion of antibiotics, medications that have been in use for more than 80 years, but only now have consensus guidelines been proposed on prescribing the drugs for patients with substantial fat mass.

The new research arrives amid two major global health crises: In 2022, the World Health Organization declared that 43% of the global adult population is overweight, and an estimated 16% of adults are considered obese, some severely so. Also, in recent years, the WHO has stressed the need for more efficient use of antibiotics to preserve their usefulness as drug-resistant superbugs become an increasingly lethal threat.

Now, an international team of medical investigators reports that obesity can interfere with antibiotics, resulting in too much or too little drug exposure to treat infections. And because dosages that effectively work in normal weight individuals don’t seem to treat the obese, the research team has developed obesity-specific antibiotic dosing guidelines for certain classes of the drugs.

Writing in The Lancet Infectious Diseases, the team describes its research as an in-depth systematic review of the medical literature on dosing and antibiotics. Conclusions drawn from the research created the framework for the guidelines.

“Obesity can alter antibiotic pharmacokinetics due to physiological changes, such as body composition and organ dysfunction that result in increased or decreased drug exposures in plasma or at the site of infection,” writes lead author Dr. Anne-Grete Märtson, a pharmacological researcher at Leiden University in the Netherlands. Along with her colleagues, Märtson makes a powerful case for obesity-based antibiotic dosing guidelines.

Researchers used the standard definition of obesity, a BMI of 30 or higher, and underscored that “substantial changes can occur in the volume of [systemic antibiotic] distribution due to increased fat and muscle mass.” In other words, obesity can alter how antibiotics are absorbed, distributed and excreted from the body.

The team began its systematic investigation with a review of 6,113 studies on obesity and antibiotic dosing. After eliminating duplicate studies, the team narrowed that number to 128 studies from which conclusions in the study were drawn.

A pictorial chart in the study illustrated problems facing the obese when it comes to taking antibiotics: increased fat mass, impaired kidney and/or liver function. Of special concern in the liver is the dysfunction of cytochrome P450, the group of enzymes responsible for metabolizing drugs.

Märtson and her collaborators studied a number of antibiotic classes and how body weight affects the drugs’ metabolism. Drug classes analyzed in the study included β-lactams, aminoglycosides, glycopeptides, lipoglycopeptides, and quinolones, among others. Yet, not all antibiotics require special guidelines for the obese.

“Obesity modestly alters the pharmacokinetics of β-lactam antibiotics, so evidence does not support routine dose adjustments [because of body weight],” Märtson and colleagues emphasized in the study. “For aminoglycosides and glycopeptides, the impact of obesity on pharmacokinetics is evident and weight-based dosing is recommended.”

β-lactam antibiotics include such widely prescribed drugs as the penicillins, cephalosporins, carbapenems and monobactams. They are chemically characterized by a β-lactam ring in their chemical structure. The drugs are used against a wide range of bacterial infections, including Gram-positive and Gram-negative species. But there’s no need to treat obese patients differently when it comes to β-lactam medications.

Doctors, meanwhile, frequently turn to aminoglycosides to treat extremely serious infections, especially those caused by Gram-negative bacteria. Aminoglycosides include such medications as gentamicin, streptomycin, and neomycin. These drugs work by disrupting critical protein production activity inside the bacterial cell. The drugs enter bacteria and bind to the 30S ribosomal subunit, resulting in flawed protein synthesis and death of the pathogens.

Guidelines were recommended for the use of this class in the obese as well as for glycopeptide antibiotics, which include the highly potent cell-wall-disrupting drug vancomycin.

“Maintenance doses [of vancomycin] should be individualized and guided by therapeutic drug monitoring to increase the probability of achieving therapeutic yet non-toxic drug exposures,” Märtson and her collaborators wrote.

The team did not provide a guideline based on total body weight for the quinolones, the drug class that includes the fluoroquinolones. However, the team’s recommendations stressed special consideration for administering fluoroquinolones.

“Higher or more frequent dosing resulting in higher systemic exposure should be considered for patients with obesity and severe deep-seated infections to reach adequate tissue concentration,” the team asserted.

Data were sparse for other antibiotic classes and will require additional study, according to findings from the research.

Recommendations for dose adjustments were drafted by Märtson and Dr. Thomas Tängdén of Uppsala University in Uppsala, Sweden. They worked with a far-flung group of collaborators from around the world to create guidelines to be recognized globally.

Team members hailed from the United States, Belgium, Austria, Germany, and Australia. Scientists from major European study groups and global scientific societies also participated. Among them are the Pharmacokinetics and Pharmacodynamics of Anti-Infectives Study Group of the European Society of Microbiology and Infectious Diseases; the International Society of Anti-Infective Pharmacology, and the Society of Infectious Diseases Pharmacists.

“When making decisions on dosing in obesity, the severity of illness, site of infection, susceptibility of the pathogen, and potential toxicity of the antibiotics should be considered,” Märtson and colleagues concluded. “In the absence of robust pharmacokinetic data to inform dose adjustments, therapeutic drug monitoring can be useful to guide individualized dosing.”

© 2025 Science X Network