A recent study published in the Journal of the American Medical Association Network Open revealed that the use of empiric broad-spectrum antibiotics has augmented among patients with suspected community-onset sepsis, including those with no evidence of antimicrobial-resistant pathogens.

The authors wrote, “Little is known about the degree to which suspected sepsis drives broad-spectrum antibiotic use in hospitals, what proportion of antibiotic courses are unnecessarily broad in retrospect, and whether these patterns are changing over time.”

In this cross-sectional study, researchers employed clinical data from adults admitted to 241 U.S. hospitals in the PINC AI Healthcare Database and sought to characterize trends in empiric broad-spectrum antibiotic use for suspected community-onset sepsis.

Eligible participants were aged 18 years or older and were admitted between 2017 and 2021 with suspected community-onset sepsis, defined by a blood culture draw, lactate measurement, and IV antibiotic administration on admission.

Broad-spectrum antibiotics were defined as those with activity against Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus (MRSA). The primary outcomes included annual rates of empiric anti-MRSA and/or antipseudomonal β-lactam agent use and the percentage that was likely unnecessary in retrospect based on the absence of resistant pathogens. Mixed-effects logistic regression models were employed to compute annual trends.

The study cohort was comprised of 6,272,538 patients (median age, 66 years [interquartile range, 53-78] years of which 443,465 were male [49.6%]; 106,095 were black [11.9%], were 65,763 Hispanic [7.4%], and 653,907 were white [73.1%]) were included in the final analysis, of whom 894,724 (14.3%) had suspected sepsis at admission.

Among the 582,585 patients with suspected sepsis who received treatment, 42.5% were administered empiric anti-MRSA therapy, 57.4% received antipseudomonal β-lactam therapy, and 34.8% were treated with both agents. Of these patients, 30,617 (3.4%) had resistant gram-positive pathogens, 38,844 (4.3%) had resistant gram-negative pathogens, and 65,434 (7.3%) had either resistant gram-positive or gram-negative pathogens.

During the study period, patients with suspected community-onset sepsis accounted for nearly one-half of all anti-MRSA and antipseudomonal β-lactam days of therapy (50.1% and 49.3%, respectively) administered across all hospitalizations. The researchers also observed increased rates of broad-spectrum antibiotic administration for community-onset sepsis in this period (from 63% to 66.7%; adjusted odds ratio [aOR] per year, 1.03; 95% CI, 1.03-1.04), which was principally driven by antipseudomonal β-lactam use.

Between 2017 and 2021, the percentage of suspected sepsis episodes with evidence of resistant gram-positive and gram-negative pathogens diminished from 3.9% to 3.0% (aOR per year, 0.93; 95% CI, 0.92-0.94) and from 6.2% to 3.7% (aOR per year, 0.84; 95% CI, 0.83-0.85), respectively. Comparable findings were detected over the same timeframe regarding the rate of suspected sepsis episodes with evidence of either resistant gram-positive or gram-negative pathogens (from 9.6% to 7.3%; aOR per year, 0.87; 95% CI, 0.87-0.88).

Overall, most patients (90.5%) who received empiric broad-spectrum antibiotics had no evidence of gram-positive or gram-negative resistance. Moreover, the rate of unnecessary broad-spectrum antibiotic use for suspected sepsis increased from 88% in 2017 to 91.6% in 2021 (aOR per year, 1.12; 95% CI, 1.11-1.13).

Further analysis of patients with suspected sepsis disclosed that the rate of inappropriately narrow treatment remained steady over time for those with resistant gram-positive pathogens (aOR per year, 0.98; 95% CI, 0.96-1.00) but diminished for those with resistant gram-negative pathogens (aOR per year, 0.89; 95% CI, 0.87-0.90).

The authors concluded that in this cross-sectional study, empiric broad-spectrum antibiotic use for suspected community-onset sepsis accounted for one-half of all anti-MRSA or antipseudomonal therapy. Moreover, the utilization of these types of antibiotics expanded between 2017 and 2021 despite resistant organisms being isolated in less than 10% of patients treated with broad-spectrum agents.

The authors wrote, “These results suggest that more attention is needed toward balancing early broad-spectrum antibiotic prescribing for patients with sepsis with limiting overuse for the majority who do not have antibiotic-resistant infections.”

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