While obesity is frequently associated with a number of health risks, including diabetes, heart disease, and stroke, it is also associated with increased risk of infectious disease complications. Two articles in the March 2017 issue of Antimicrobial Agents and Chemotherapy cover studies that reveal the risk obesity confers to treating infectious disease and how modifying treatment for obese patients could improve resolution of infection.
The first study looked at patients with outpatient skin infections, such as cellulitis, which are increasing in occurrence within the United States. These infections are often treated with an oral antibiotic prescription given after a medical examination, but as many as one-fifth the people treated fail their first antibiotic course. The authors wanted to find factors that contribute to antibiotic failure, so doctors might better predict how patients will respond to treatment.
The research team, lead by first author Erin Conway and senior scientist Kari Mergenhagen, looked at de-identified patient records to find those who had been treated for cellulitis, abscesses, and mixed cellulitis and abscesses. Within this patient group, 24% had failed oral antibiotics and required either an additional antibiotic or hospitalization within a month of the initial treatment. Doctors took into consideration the patient age, race, height, temperature, serum creatine, creatine clearance, and weight to find factors affecting antibiotic failure. The sites and types of infections were similar among those whose infections were successfully treated and those who failed treatment.
The AAC study found an association between antibiotic failure and both heart failure and BMI.
Statistical analyses found that BMI and heart failure were the most significant factors in predicting antibiotic failure (see table, right). Each 10-unit increase in body mass index (BMI) was associated with a 1.62-fold increased changes of failing therapy, while heart failure was associated with a 2.56-fold increase. The authors concluded with recommendations to address this problem through optimization of antibiotic doses and duration to prevent treatment failure.
The second study addresses antibiotic optimization by focusing specifically on piperacillin, a β-lactam antibiotic that kills bacteria in a time-dependent manner. Because of its time dependence, the half-life of piperacillin in the body can affect its efficacy. The research team, led by first author Abdulaziz Alobaid and senior scientist Jason Roberts, tested the effect of body weight and kidney function on piperacillin half-life in people.
This study recruited 37 patients evenly distributed among nonobese, obese, and extremely obese, based on their BMI. In their statistical analyses, the research team found that drug clearance affected by both BMI and by patients’ creatine clearance (CLCR) rate, a measure of kidney function. Although patients with a high BMI had slower clearance of the drug, the ability of the drug to meet the minimal inhibitory concentration (MIC) to be effective was negatively affected by a high BMI. A high CLCR in patients with a healthy BMI also had a strong negative affect on the MIC.
The researchers also tested the effect of different dosing strategies, looking at patients dosed every 4, 6, or 8 hours. These analyses showed that frequent (every 4 hours) or continuous infusions can normalize the effects of BMI or kidney function, and the authors suggest health care workers adjust the dosing regiment for patients based on renal function and BMI: more prolonged infusions for high BMI or high CLCR patients, and less-frequent infusions for low-BMI and low-CLCR patients. This would help ensure the drug remained in the patient’s system long enough to be effective.
Both of these studies are part of an important effort to recognize the effects of body weight on the treatment of infectious disease. With two-thirds the United States population considered overweight and a third considered obese (and two-thirds the population considered overweight in Australia, where the second study was conducted), understanding how to treat this segment of the population is important for the best health outcomes. Similar studies for all antibiotics (including those used in combination) will be useful, but these initial studies highlight that factoring in a patient’s weight and kidney function when setting dosing strategies can lead to better disease outcomes.