The Journal of antimicrobial chemotherapy · 2026
Impact of loading dose β-lactam therapy on outcomes of KPC-producing Klebsiella pneumoniae bloodstream infections in non-ICU patients: a real world study.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Frallonardo Luisa, Guido Giacomo, De Gennaro Nicolò, De Iaco Giuseppina, Signorile Fabio, Cibelli Marinella, De Luca Antonio, Ritacco Annunziata Ilenia, Stolfa Stefania, Di Gennaro Francesco, Saracino Annalisa
Аннотация
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.
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.