Reviewed by: David Cluck, PharmD; East Tennessee State University
How to reconcile the findings of this study when juxtaposed with the findings of the BLING-3 study results is difficult.1,2 However, it would be shortsighted to conclude that prolonged infusion β-lactam therapy has no role or benefit in certain patient populations. Continuous and/or extended infusion β-lactam therapy is recommended for difficult to treat organisms in the current IDSA Gram-negative guidance, many of whom are likely to be critically ill.3 Larger studies are needed to evaluate the possible benefit of using prolonged infusion β-lactam therapy to prevent the emergence of resistance.
Karaba and colleagues evaluated the use of extended infusion β-lactam therapy to determine the impact on mortality, adverse events and emergence of antibiotic resistance in patients with gram-negative bacteremia.1 The primary endpoint was 90-day mortality from blood culture collection. A total of 4861 patients were enrolled from 24 centers in the US in 2019. Emergence of resistance was defined as a 4-fold increase in the minimum inhibitory concentration (MIC) of the β-lactam used to treat the index gram-negative bacteremia. To account for confounding, extended infusion β-lactam (EI-BL) and intermittent infusion β-lactam (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 most common patient enrolled was a male in their late 60s with E. coli bacteremia. 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 ([aOR], 0.71 [95% CI, 0.52-0.97], P = .03). Notably, a survival benefit was only shown in patients with severe illness or elevated MICs (aOR, 0.06 [95% CI, 0.01-0.66]; P = .02). The benefit was not seen in patients with more susceptible isolates. There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, AKI, cytopenias, seizures) in the EI-BL group (aOR,3.66 [95% CI, 1.68-7.95]). Emergence of resistance was numerically lower in the EI-BL group, but this was not statistically significant (P = .35).
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