Impact of loading dose β-lactam therapy on outcomes of KPC-producing <i>Klebsiella pneumoniae</i> bloodstream infections in non-ICU patients: a real world study

BACKGROUND: Bloodstream infections (BSIs) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) remain associated with high mortality, even outside intensive care units (ICUs). Optimizing early β-lactam exposure through a loading dose (LD) of ceftazidime-avibactam or meropenem-vaborbactam may improve outcomes, but evidence in non-ICU settings is limited. METHODS: We conducted a retrospective single-centre study (January 2023-June 2025) including adult non-ICU inpatients with genotypically confirmed KPC-Kp BSI. The control group received standard dosing (ceftazidime-avibactam 2 g/0.5 g q8h or meropenem-vaborbactam 2 g/2 g q8h, both over 3 h). The LD group received either one standard dose infused over 30 min (Scheme A) or one standard dose + 50% infused over 2-3 h (Scheme B), followed by the standard regimen q8h. Primary outcomes were 7- and 30-day all-cause mortality; secondary outcomes included microbiological clearance ≤72 h, ICU transfer and/or vasopressor use, adverse events (AEs ≥ grade 2), hospital stay, and recurrence ≤30 days. RESULTS: A total of 189 patients were included (140 controls, 49 LD). Groups were comparable in age (median 74 years), comorbidities (Charlson 5), and renal function (eGFR ≈45 mL/min/1.73 m²). LD was associated with faster blood-culture clearance (78% versus 55%; RR 1.26, 95% CI 1.03-1.61, P = 0.02) and lower ICU/vasopressor requirement (7.5% versus 23%; RR 0.60, 95% CI 0.29-0.93, P = 0.02). Median hospital stay was shorter (33 versus 37 days, P = 0.3). Thirty-day mortality was lower in LD (16.3% versus 21.0%; adjusted RR 0.62, 95% CI 0.39-1.29, P = 0.23), indicating a non-significant but clinically relevant trend. No increase in adverse events or nephrotoxicity was observed. CONCLUSIONS: In non-ICU KPC-Kp BSIs, a β-lactam loading dose regimen was associated with faster microbiological clearance, reduced ICU transfer and shorter hospital stay, without added toxicity. Mortality showed a non-significant trend towards improvement. Pragmatic LD strategies may enhance early β-lactam exposure where therapeutic drug monitoring (TDM) is unavailable. Prospective PK/PD-guided studies are warranted.