Obese may need larger drug doses

“Patients may have to be prescribed higher doses of antibiotics because of rising rates of obesity,” BBC News has reported.

The story is based on a narrative review in The Lancet. The authors say that drugs for treating infection should be prescribed according to body weight (as is the case when prescribing for children). They state that this may turn out to be advantageous to the person taking the drugs, the healthcare provider and the fight against disease in general.

Microbes that are resistant to antibiotics, antivirals or antifungals are a genuine concern. If dosing that is tailored for individuals helps to prevent resistance, then it should be considered. However, changes to current prescribing would be costly and complex. More research is now needed, investigating if the benefits of tailored dosing are enough to warrant a change to current practice.

Where did the story come from?

Dr Matthew Falagas and Drosos Karageorgopoulos of the Alfa Institute of Biomedical Science, Athens, Greece, carried out this research. There was no funding provided for this narrative review. The study was published in the peer-reviewed medical journal_ The Lancet._

This narrative review was accurately reflected in the news reports.

What kind of research was this?

This narrative review presents the authors’ views and experiences about how adult body weight may need to be taken into consideration when prescribing antimicrobials. It should not, therefore, be interpreted as a systematic review or original research. Whether or not tailored dosing for overweight and obese adults reduces the time it takes to clear infection will need further research and follow-up in a variety of adult populations.

What did the research involve?

The authors describe how advances in molecular biology and pharmacology have enabled the development of drug treatments that are tailored for individual patients. However, although the patient's body size needs to be taken into account for drug treatments to be of most benefit, they say that most dosing regimens, across medical specialties, do not currently take this into consideration.

The authors say that body size varies substantially around the world. The ‘modern epidemic’ of obesity, affecting more than 30% of people in the US and 20% of people in several European countries, needs to be taken into account.

The main discussion points

The authors say that, although pharmacokinetic studies (studies of how drugs are distributed, processed and disposed by the body) consider different ages and diseases, body size and other characteristics also need to be taken into account:

• Physiological alterations to the body, such as increased adipose (fat) tissue, can affect distribution, metabolism and clearance of drugs from the body. In particular, different considerations need to be given to hydrophilic (‘water-loving’) and lipophilic (‘fat-loving’) drugs, as these have different distributions in obese and lean people. Body size may also have an effect on liver and kidney function, with obesity believed to increase clearance of drugs.
• Available data support the notion that several antimicrobial drugs that are currently given in standard doses, should be given in higher doses to patients with large body size to help attain target effects on the body. These include β-lactams, vancomycin, fluoroquinolones, macrolides, linezolid, sulphonamides, fluconazole, aminoglycosides, daptomycin, colistin, and amphotericin B, co-trimoxazole, metronidazole and aciclovir.
• However, the complex interaction between different drugs and body size means that a standard calculation would be difficult to establish. There are many factors that could be relevant, such as body mass index (BMI), total weight, adjusted weight (fraction of excess body weight added to ideal weight), lean body weight and body surface area. For different drugs, different factors may need to be considered to calculate the right dose. This is also the case for underweight people.
• Based on the class of drug and its weight-dependent body distribution and clearance, some drugs may need to be given at greater or lesser amounts than the standard adult dose. Some drugs may need their starting dose adjusted, while others may need to have their maintenance dose changed. Others may benefit from being given at the standard dose but for a shorter or longer duration.
• Such tailored doses may be beneficial for preventing antimicrobial resistance, and preventing suppression of normal ‘friendly’ bacterial flora in the body, in addition to giving maximum effectiveness and safety for the patient.

What did the researchers conclude?

The researchers suggest that all available published or unpublished pharmacokinetic data should be reassessed with the aim of identifying the most appropriate dosage adjustments for adults depending on their body weight. Further clinical trials would be needed to confirm that these readjusted doses are safe and effective for use.

Conclusion

This is a valuable discussion, which raises several important issues in the use of drugs to treat infection. The headlines should not be interpreted to mean that obese people are putting extra demand on antimicrobial supplies. The issue is that a dose tailored to body weight may be advantageous to the person, the healthcare provider and the fight against disease in general. The development of microbes that are resistant to antibiotics, antivirals or antifungals is a genuine concern. If individual patient-dosing would help to prevent this resistance, then these suggestions should be considered.

Another important issue is the minimisation of side effects. Clearance of infection is obviously an important outcome for the person taking the drugs, but just as important is avoiding any adverse effects or depleting levels of normal bacteria that live in the body, which can, in itself, lead to other infections. This risk can be reduced by not exposing patients to unnecessary drugs, and by ensuring that if antimicrobials are needed, they are not given for prolonged periods of time or in consecutive courses.

The researchers suggest that dosage adjustments according to body size and body composition should become “an integral part of the process of new antimicrobial drug development”, and this appears to be a worthy argument. However, as they have discussed, it may not be as easy as making one simple adjustment for body weight, and different methods may be needed for different drugs. In addition, changes to current prescribing would have considerable cost and practice implications that need to be considered.

A review of previous study data, as well as new clinical trials that dose according to body weight and that follow-up effects would be needed to see if the benefits are substantial enough to warrant a change to current practice for all prescribed drugs.