Antibiotic Failure: A Weighty Issue in Patients with Obesity

Obesity is a worldwide and fast-growing epidemic and a major public health concern in the developed world.¹ Increasing rates of obesity are responsible for a dramatic increase in obesity-related mortality, with obesity now recognized as the second leading cause of preventable death in the United States.²

It is well established that obesity is a risk factor for cardiovascular disease, hypertension, certain types of cancer, and type 2 diabetes.³ Recent research has shown that obesity also compromises immune response and is associated with high rates of infection.⁴ Obese patients experience higher rates of infection-related hospital mortality⁵ than do their non-obese counterparts. Frequent infections in obese patients lead to more frequent use of antibacterial medications in this population than in those who are not obese.⁶

In people who are overweight, antibiotic medications have an “altered drug disposition profile” that affects their ability to attain therapeutic targets. ⁷ Recent pharmacokinetic evidence suggests that excess adiposity “dramatically increases” the volume of distribution (Vd) and clearance (CL) of antibacterial medications, since both hydrophilic and lipophilic antibiotics readily distribute into adipose tissue, which reduces the amount of unbound drug available for pharmacologic activity at the site of the infection.⁷ These abnormalities in Vd and CL therefore can cause suboptimal drug concentrations of antibiotics in the blood, leading to dose inadequacy and resulting antibiotic treatment failure (ATF).⁷

A recent population-based study explores the relationship between obesity and ATF.⁷ The researchers conducted a retrospective analysis of 6,179 patients, comparing those without ATF (N=5351) to those with ATF (N=828) to determine whether overweight and obese patients had a higher proportion of ATF than their non-obese counterparts.

“Overweight” was defined as a BMI of 25.0-29.9 kg/m2 and “obesity” as a BMI of >30 mg/m2. A “first” antibiotic prescription was defined as the “first orally administered antibiotic issued following the date of health survey completion.” A “first” hospitalization for infection was defined as “any acute care hospital admission with a length of stay (LOS) of 30 days or less for an infection… requiring a short course of antibiotic therapy (<21 days).” ATF was measured as “additional or modified antibiotic prescriptions or hospitalizations with acute infection as a primary or secondary cause of admission within 30 days following initial treatment for infection.”⁷ The time at which the first antibiotic was dispensed, or the discharge date of the first hospitalization, was referred to as “T0.”

The authors took several variables into account, in addition to BMI category, including comorbidities, lifestyle factors (smoking and drinking), time of year of initial antibiotic prescription (such as “flu season”), methicillin-resistant staphylococcus aureus (MRSA), history of antibiotic use, age, sex, and income.

The researchers found that 5,903 patients (95.5%) received an oral antibiotic, and 276 (4.5%) were hospitalized for acute infection at T0. Amoxicillin was the most commonly prescribed antibacterial agent for all patient populations—normal, overweight, and obese—followed by ciprofloxacin. Other antibiotics were phenoxymethylpenicillin, trimethoprim/sulfamethoxazole, clarithromycin, azithromycin, cloxacillin, cefuroxime, erythromycin, metronidazole, doxycycline, and cephalexin. Of note, overweight patients were the only group treated with doxycycline, and obese patients were the only group treated with cephalexin.

The most common infectious indications for antibacterial therapy at T0 (in descending order) were upper respiratory tract infections (URTIs), lower respiratory tract infections (LRTIs), skin and soft tissue infections (SSTIs), urinary tract infections (UTIs), gastrointestinal tract infections (GTIs), genitovenereal infections, abscesses, infectious of unspecified causes, and eye/ear infections. Only 4.9% (N=303) of all infection diagnoses were considered to be MRSA-SSTIs.

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