Original Investigation
Infectious Diseases
July 2, 2024
Extended-Infusion β-Lactam Therapy, Mortality, and Subsequent Antibiotic Resistance Among Hospitalized Adults With Gram-Negative Bloodstream Infections
Sara M. Karaba, Sara E. Cosgrove, Jae Hyoung Lee, et al
JAMA Netw Open. 2024;7(7):e2418234. doi:10.1001/jamanetworkopen.2024.18234
Question Is extended-infusion β-lactam (EI-BL) therapy associated with mortality, adverse events, and the subsequent emergence of antibiotic resistance in patients with gram-negative bloodstream infections (GN-BSI)?
Findings In this cohort study of 4861 adults with GN-BSI, EI-BL therapy was associated with reduced mortality among patients with severe illness and/or antibiotic minimum inhibitory concentrations in the intermediate range to the β-lactam agent administered for treatment. There were increased odds of catheter complications and antibiotic discontinuation due to adverse events in the EI-BL group; and the emergence of antibiotic resistance was similar in the EI-BL and intermittent infusion β-lactam groups.
Meaning These results suggest that patients with GN-BSI who are severely ill or infected with bacteria with elevated antibiotic minimum inhibitory concentrations may benefit from EI-BL therapy.
Abstract
Importance Current evidence is conflicting for associations of extended-infusion β-lactam (EI-BL) therapy with clinical outcomes.
Objective To investigate the association of EI-BL therapy with survival, adverse events, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections (GN-BSI).
Design, Setting, and Participants This cohort study of consecutive adults with GN-BSI admitted to 24 United States hospitals between January 1, 2019, and December 31, 2019, receiving EI-BL were compared with adults with GN-BSI receiving the same agents as intermittent infusion β-lactam (II-BL; ≤1-hour infusions). Statistical analysis was performed from January to October 2023.
Exposures EI-BL (ie, ≥3-hour infusion).
Main Outcomes and Measures EI-BL and II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to investigate outcomes, all censored at day 90. The primary outcome was mortality; secondary outcomes included antibiotic adverse events and emergence of resistance (≥4-fold increase in the minimum inhibitory concentration of the β-lactam used to treat the index GN-BSI).
Results Among the 4861 patients included, 2547 (52.4%) were male; and the median (IQR) age was 67 (55-77) years. There were 352 patients in the EI-BL 1:3 PSM group, and 1056 patients in the II-BL 1:3 PSM group. Among 1408 PSM patients, 373 (26.5%) died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (ie, in the intermediate range for the antibiotic administered). There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66 [95% CI, 1.68-7.95]). Emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% vs 7.2%, respectively (P = .35).
Conclusions and Relevance In this cohort study of patients with GN-BSI, EI-BL therapy was associated with reduced mortality for patients with severe illness or those infected with nonsusceptible organisms; potential advantages in other groups remain unclear and need to be balanced with potential adverse events. The subsequent emergence of resistance warrants investigation in a larger cohort.
