Research suggests obesity can interfere with the effectiveness of antibiotics for humans, resulting in too much or too little drug exposure, according to a new systematic review of obesity and antibiotic dosing studies by a team of medical researchers.
This systematic review was conducted to “extract and compile evidence to guide antibiotic dose adjustments in patients with obesity.”
The review, published in The Lancet Infectious Diseases on May 15, proposed “consensus guidelines” for prescribing antibiotics to obese patients, describing their research as “in-depth systematic review of the medical literature on dosing and antibiotics.”
Obesity can alter how antibiotics are distributed within the body due to physiological changes such as body composition or even organ dysfunction.
“Substantial changes can occur in the volume of distribution due to increased fat and muscle mass, and tissue drug concentrations might be lowered,” the review says.
Mahyar Etminan, a drug safety epidemiologist with EpiLytics Consulting who was not involved in the research but reviewed the publication, explained that obese patients need higher dosages of antibiotics due to the high levels of body tissue.
“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,” Etminan told CTVNews.ca, adding that you should use antibiotics that have a higher tissue penetration, “so they can get into the tissue more than water soluble antibiotics.”
The researchers based their analysis on people aged 18 years and higher with a higher Body Mass Index than 30.
The main difference is in the functioning of the receptors that these drugs work on, Etminan said.
Higher doses?
“In obese individuals, you have higher body mass, so the drug has to get into the tissue (and) has to travel to more tissue than a non-obese patient,” he said. “That usually means higher doses, use of more penetrating antibiotics and looking into other parameters.”
The researchers studied several antibiotic drug classes and the effect of body weight on the manner in which the drugs were absorbed. However, they found that there were some classes of antibiotics, depending on the characteristics, that did not require special instructions for people who were overweight.
β-lactam, a class of antibiotics typically used to treat a wide range of acute bacterial infections do not require any special guidelines to be enforced, based on weight class.
“Obesity modestly alters the pharmacokinetics of β-lactam antibiotics, but evidence does not support routine dose adjustments,” the review states.
The review also goes on to caution that aggressive dosing of β-lactams can also result in toxic drug concentrations and side-effects, the review cautions.
Meanwhile, aminoglycosides and glycopeptides, classes of antibiotics often prescribed by doctors to treat extremely serious infections need to follow the recommended guidelines for obesity-based dosages.
“Therapeutic drug monitoring and the monitoring of creatinine clearance are highly recommended to guide maintenance dosing,” the review recommended.
Due to the absence of enough empiric data, therapeutic monitoring of the drugs could prove useful based on each individual patient, it said.
Anne-Grete Märtson, a pharmacological researcher at Leiden University in the Netherlands, and her team reviewed 6,113 studies on obesity and antibiotic dosing, of which 128 fit the criteria for the research. Fifty-seven were focused on β-lactam antibiotics and 45 focused on glycopeptides, lipoglycopeptides, and oxazolidinones, according to the review.
However, additional studies are required for other types of antibiotic classes to obtain conclusive information, the team noted.
“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,” the review concluded.
“In the absence of robust pharmacokinetic data to inform dose adjustments, therapeutic drug monitoring can be useful to guide individualized dosing.”
Märtson and Thomas Tängdén of Uppsala University in Uppsala, Sweden, along with a group of collaborators from around the world drafted this recommendation for dose adjustments.
The research team members were from the U.S., Belgium, Austria, Germany and Australia.
