Patients with morbid obesity receiving novel β-lactam/β-lactamase inhibitor combinations for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by Pseudomonas aeruginosa are at increased risk for presumed treatment failure compared with those without morbid obesity, according to study results published in Open Forum Infectious Diseases.
This retrospective cohort study was designed to examine the effect of morbid obesity in adults who received β-lactam/β-lactamase inhibitor combinations for P aeruginosa-associated HABP/VABP at 2 academic medical centers in Detroit, Michigan from August 2014 to February 2021. Researchers assigned 285 patients into 2 groups on the basis of BMI, including those with morbid obesity (n=95) and those without morbid obesity (n=190). The primary outcome was a composite of presumed treatment failure, defined as all-cause in-hospital mortality or persistent infectious symptoms attributed to P aeruginosa-associated HABP/VABP.
The researchers captured data on patients’ characteristics, demographics, and comorbidity burden at baseline. Organ function and illness severity were also assessed via electronic health record data captured within 48 hours prior to or on the same day of primary culture collection. The researchers also generated propensity scores through multivariable logistic regression to ensure unbiased comparisons between the groups.
Among patients with and without morbid obesity, the median ages were 64 and 61 years, 54.7% and 72.6% were men (P =.003), and 91.6% and 80.5% required intensive care unit admission (P =.016), respectively. Overall, the most common comorbid conditions included chronic obstructive pulmonary disease/asthma (31.6%), heart failure (20.4%), and chronic kidney disease (23.2%).
Further analysis was performed among a pseudo-population, with between-group differences in covariate biases balanced via inverse probability of treatment weighting. Results indicated an increased risk for presumed treatment failure among patients with morbid obesity (adjusted odds ratio [aOR], 1.675; 95% CI, 1.465-1.979).
In the multivariable logistic regression model, predictors of presumed treatment failure included delayed treatment initiation (aOR, 1.47; 95% CI, 1.28- 2.66) and receipt of continuous kidney replacement therapy (aOR, 1.35; 95% CI, 1.06, 1.49).
The researchers noted no difference in the occurrence of treatment-related adverse events between groups.
Limitations of the study include its retrospective design, potential confounding, and a lack of generalizability as patient enrollment occurred at 2 large health care systems in a single metropolitan area. These findings also may not be generalizable to populations in which alternative definitions of obesity are applied.
According to the researchers, “Therapeutic drug monitoring (TDM)-based dosing coupled with modified dosing administrations may be warranted for select scenarios to achieve PD [pharmacodynamic] targets, including in critically ill obese patients.”
Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Kunz Coyne AJ, Orzol C, Veve MP, Rybak MJ. Weighing the odds: Novel beta-lactam/beta-lactamase inhibitor use in morbidly obese patients with pseudomonas aeruginosa HABP/VABP. Open Forum Infect Dis. Published online August 28, 2023. doi:10.1093/ofid/ofad454