TOPLINE:

Among non-ICU patients with bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae, a loading dose regimen of ceftazidime-avibactam or meropenem-vaborbactam was associated with faster microbiological clearance and fewer transfers to the ICU, with no increase in toxicity.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using real-world data to determine whether a loading dose regimen of ceftazidime-avibactam or meropenem-vaborbactam improved early clinical and microbiological outcomes in non‑ICU inpatients with bloodstream infections caused by carbapenemase-producing K pneumoniae.
• They included 189 patients (median age, 74 years; 57% men) from a tertiary hospital in Italy who had at least one positive blood culture for carbapenemase-producing K pneumoniae; patients were divided into two groups: a loading dose group and a standard dose group.
• The standard dose group (n = 140) received ceftazidime-avibactam or meropenem-vaborbactam according to routine practice. The loading dose group (n = 49) received either a single standard dose infused over 30 minutes or a standard dose plus an additional 50% dose administered over 2-3 hours; both approaches were followed by the standard dose every 8 hours.
• Primary outcomes were 7-day and 30-day all-cause mortality; secondary outcomes included microbiological clearance within 72 hours, transfer to the ICU and/or vasopressor use, and adverse events of grade 2 or higher.

TAKEAWAY:

• All-cause mortality tended to be lower in the loading dose group than in the standard dose group at 7 days (8.2% vs 15.0%) and at 30 days (16.3% vs 21.0%), but these differences did not reach statistical significance.
• The loading dose regimen was associated with faster microbiological clearance within 72 hours than the standard dose regimen (risk ratio [RR], 1.26; P = .02).
• Patients who received a loading dose regimen also had fewer transfers to the ICU and/or a lower need for vasopressors than those who received a standard dose regimen (RR, 0.60; P = .02).
• Rates of adverse events, including nephrotoxicity, were similar in both groups, and none of the patients discontinued therapy because of drug-related toxicity.

IN PRACTICE:

"Pending prospective PK [pharmacokinetics]/PD [pharmacodynamics]-guided confirmation, a LD [loading dose] regimen followed by maintenance q8h [every 8 hours] may represent a rational, safe, and readily implementable in antimicrobial strategies to optimize early [beta]-lactam exposure outside the ICU," the authors wrote.

SOURCE:

This study was led by Luisa Frallonardo, University of Bari Aldo Moro, Bari, Italy. It was published online on March 05, 2026, in the Journal of Antimicrobial Chemotherapy.

LIMITATIONS:

This retrospective single‑centre study was subject to potential residual confounding. The exclusion of patients with chronic renal failure may have limited the applicability of the findings to that population. The results may not have been generalisable to settings with different local epidemiology, particularly where ceftazidime-avibactam resistance had been documented.

DISCLOSURES:

The authors did not receive any external or internal funding for this research and disclosed having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.