Extended-Infusion beta-lactam Therapy Promising in Treating Gram-Negative Bloodstream Infections: JAMA

EI-BL therapy was associated with lower mortality in patients with severe illness and antibiotic minimum inhibitory concentrations in the intermediate range to the β-lactam agent administered for treatment, researchers reported in JAMA Network Open. Due to adverse events in the EI-BL group, there were increased odds of antibiotic discontinuation and catheter complications, and antibiotic resistance emergence was similar in the EI-BL and intermittent infusion β-lactam groups.

Gram-negative bloodstream infections pose a serious threat in hospital settings due to their resistance to multiple antibiotics, complicating treatment, and increasing mortality rates. Traditional intermittent β-lactam therapy, where antibiotics are administered over short periods, has been the standard approach. However, concerns over its efficacy in achieving optimal drug concentrations at the infection site have prompted researchers to explore extended-infusion therapy.

Against the above background, Sara M. Karaba, Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, and colleagues aimed to investigate the association of EI-BL therapy with adverse events, survival, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections.

For this purpose, the researchers conducted a cohort study of consecutive adults with GN-BSI admitted to 24 US hospitals between January 1, 2019, and December 31, 2019. They were compared with adults with GN-BSI receiving the same agents as intermittent infusion β-lactam (II-BL; ≤1-hour infusions).

The groups receiving extended-infusion beta-lactam (EI-BL) and intermittent-infusion beta-lactam (II-BL) underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to examine outcomes, all censored at day 90.

The primary outcome was mortality; secondary outcomes included antibiotic adverse events and resistance emergence (≥4-fold increase in the minimum inhibitory concentration of the β-lactam used to treat the index GN-BSI).

The following were the key findings of the study:

• Among the 4861 patients included, 52.4% were male; and the median age was 67. 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, 26.5% died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71).
• In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (i.e., in the intermediate range for the antibiotic administered).
• There were increased odds of catheter complications (aOR, 3.14) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66).
• The emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% versus 7.2%, respectively.

In conclusion, EI-BL therapy is associated with decreased mortality for patients with severe illness or those infected with nonsusceptible organisms in the cohort study of patients with GN-BSI; there is no clarity on the potential advantages in other groups, and need to be balanced with potential adverse events.

Further investigation is warranted in a larger cohort to examine the subsequent development of resistance, the researchers suggested.

Reference:

Karaba SM, Cosgrove SE, Lee JH, et al. Extended-Infusion β-Lactam Therapy, Mortality, and Subsequent Antibiotic Resistance Among Hospitalized Adults With Gram-Negative Bloodstream Infections. JAMA Netw Open. 2024;7(7):e2418234. doi:10.1001/jamanetworkopen.2024.18234