Obesity Linked to Higher Rates of Beta-Lactam Treatment Failure, Longer Hospitalization for Infection

Patients with obesity who are treated with beta-lactams experience higher rates of treatment failure and longer lengths of hospitalization compared with patients who are not obese, according to the results of a study published in Open Forum Infectious Disease.

Researchers sought to determine whether patients with obesity who receive beta-lactam experience worse clinical outcomes compared with patients without obesity, determining if the pursuit of therapeutic drug monitoring is beneficial in this patient population.

Investigators conducted a multicenter, retrospective cohort study of hospitalized adult patients from July 2015 to July 2017, treated with beta-lactam as a “definitive monotherapy” for Gram-negative bacilli infections for at least 72 hours. Patients were categorized into 1 of 2 groups based on body mass index (BMI): nonobese, with a BMI less than 29.9 kg/m² and obese, with a BMI greater than 30 kg/m².

The cohort included a total of 589 patients, with 43.6% and 56.4% in the obese and nonobese groups, respectively. In the obese group, the median weight and BMI were 102.2 kg and 35.3 kg/m2; in the nonobese group, median weight and BMI were 68.1 kg and 24.4 kg/m2, respectively.

Across the total population, median age was 70 years, 43% of patients were men, and 53% were Black. Baseline characteristics differed between the 2 groups, including age, renal function, and comorbid conditions.

The most common suspected infection sites were the urinary tract, respiratory tract, and bloodstream (55.5%, 34.3%, and 27.8%, respectively), and the most commonly administered empiric antibiotics included intravenous vancomycin (41.3%), third-generation cephalosporins (39%), cefepime (36.3%), and beta-lactam/beta-lactamase inhibitors (15.3%).

Between groups, there were significant differences in the use of empiric cefepime and beta-lactam/beta-lactamase inhibitors (30.0% vs 41.3% and 19.5% vs 12% in the obese and nonobese groups, respectively). Patients without obesity were also more likely to receive cefepime 1 g every 6 hours compared with patients with obesity (33.6% vs 14.5%).

Patients with obesity also received third-generation cephalosporins over a longer duration — 3 days vs 2 days — while patients without obesity received cefepime for 4 days vs 2 days.

Cultures were most commonly obtained from urine, blood, and sputum; more urine cultures were obtained in the nonobese group. Investigators found minimal differences in the organisms cultured between groups, with the most common final diagnoses being urinary tract infection, respiratory tract infection, and bloodstream infection (50.9%, 31.4%, and 9.3%, respectively).

A total of 39 patients had multiple infection sites, but no difference in rates of multisite infections was seen between groups.

In terms of definitive therapy, 46.9% of the patients received a third-generation cephalosporin; 44.7% received cefepime, 8% received a first-generation cephalosporin, 0.3% received an antipseudomonal carbapenem, and 0.2% received a combination beta-lactam/beta-lactamase inhibitor.

Of the total study population, 240 (40.7%) of patients experienced treatment failure: 51% of patients in the obese group and 32.8% of patients in the nonobese group. Treatment failed in the majority (75.4%) of the patients due to unresolved leukocytosis, but no differences were noted between groups.

Results of a logistic regression analysis showed that only obesity (odds ratio [OR], 2.3) and respiratory source (OR, 3.1) were independently associated with treatment failure.

Median length of hospital stay was 9 days (interquartile range, 6.0-15.5), although patients with obesity had a longer in-hospital stay vs patients without obesity (10 days vs 8 days). Just fewer than half of the patients were discharged home; 35% were discharged to a skilled nursing or rehabilitation facility, 4.2% of patients were discharged to hospice care, 1.4% to another hospital, 0.5% were still admitted, and 0.2% were discharged back to prison.

A total of 59 (10%) of patients died during hospitalization, but there were no additional deaths at 30 days postdischarge.

Study limitations included those inherent to retrospective research and the use of electronic health records to determine primary treatment failure, a lack of similarity in baseline characteristics between the obese and nonobese groups, and a broad look at beta-lactam antibiotic treatment, limiting the ability to “draw conclusions regarding specific beta-lactam dosing effectiveness.”

“[Patients with obesity] admitted for infections and treated with beta-lactam antibiotics have higher rates of treatment failure compared [with] patients [who do not have obesity],” the researchers reported. “[Patients with obesity] had greater disease burden, which hinders the ability to draw conclusions on the dosing of beta-lactam antibiotics.”

“Future studies are needed to determine specific dosing recommendations for targeted infection types, as well as using more accurate markers of treatment success, in order to adequately conclude that obesity contributes to infection-related treatment failure,” they concluded.

Disclosure: One study author declared an affiliation with a pharmaceutical company. Please see the original reference for a full list of authors’ disclosures.

Reference

Pinner NA, Tapley NG, Barber KE, Stover KR, Wagner JL. Effect of obesity on clinical failure of patients treated with beta-lactams. Open Forum Infect Dis. Published online April 27, 2021. doi:10.1093/ofid/ofab212