Background. Bloodstream infections (BSIs) caused by KPC-producing K. pneumoniae (KPC-Kp) are still associated with high mortality, and the game-changing drug ceftazidime/avibactam has shown suboptimal pharmacokinetics in some clinical settings. Ceftazidime/avibactam renal dose adjustment has recently been identified as an independent risk factor for mortality. Objectives. To investigate the effect of ceftazidime/avibactam renal dose adjustment on mortality. Methods. Patients with KPC-Kp BSI treated with a ceftazidime/avibactam-based regimen were retrospectively collected and analysed. The primary outcome was mortality at 7, 14 and 30 days after the start of definitive ceftazidime/avibactam antibiotic therapy. Renal function was estimated using the CKD-EPI equation. Results. One hundred and ten patients with KPC-Kp BSI treated with a ceftazidime/avibactam-based regimen were included. Full-dose ceftazidime/avibactam (7.5 g daily) was prescribed to eighty-two patients (74.5%), while 28 patients (25.5%) received a renal-adjusted dose (17 patients due to chronic renal disease or haemodialysis, 11 patients due to infection-related acute kidney injury), with a median of 1.9 g daily. At multivariable analysis, receiving a reduced dose of ceftazidime/avibactam was independently associated with mortality (HR 4.47, 95% CI 1.09-18.03, p=0.037), along with intra-abdominal or lower respiratory tract infections as source of BSI (HR 5.42, 95% CI 1.77-16.55, p=0.003), septic shock (HR 6.99, 95% CI 1.36-35.87, p=0.020) and SARS-CoV2 coinfection (HR 10.23, 95% CI 2.69-38.85, p=0.001). Conclusions. Dose reduction of ceftazidime/avibactam according to renal function in patients with KPC-Kp BSI seems to be independently associated with higher mortality. This may be possibly due to inadequate exposure provided by the recommended doses for renal impairment.

Impact of renal-adjusted ceftazidime/avibactam in patients with KPC-producing K. pneumoniae bloodstream infection: a retrospective cohort study / Oliva, Alessandra; Volpicelli, Lorenzo; Gigante, Antonietta; Di Nillo, Michela; Trapani, Silvia; Viscido, Agnese; Sacco, Federica; Mastroianni, Claudio. - In: JAC-ANTIMICROBIAL RESISTANCE. - ISSN 2632-1823. - (2024). [10.1093/jacamr/dlae201]

Impact of renal-adjusted ceftazidime/avibactam in patients with KPC-producing K. pneumoniae bloodstream infection: a retrospective cohort study

Alessandra Oliva
Conceptualization
;
Lorenzo Volpicelli;Antonietta Gigante;Michela Di Nillo;Silvia Trapani;Agnese Viscido;Federica Sacco;Claudio Mastroianni
2024

Abstract

Background. Bloodstream infections (BSIs) caused by KPC-producing K. pneumoniae (KPC-Kp) are still associated with high mortality, and the game-changing drug ceftazidime/avibactam has shown suboptimal pharmacokinetics in some clinical settings. Ceftazidime/avibactam renal dose adjustment has recently been identified as an independent risk factor for mortality. Objectives. To investigate the effect of ceftazidime/avibactam renal dose adjustment on mortality. Methods. Patients with KPC-Kp BSI treated with a ceftazidime/avibactam-based regimen were retrospectively collected and analysed. The primary outcome was mortality at 7, 14 and 30 days after the start of definitive ceftazidime/avibactam antibiotic therapy. Renal function was estimated using the CKD-EPI equation. Results. One hundred and ten patients with KPC-Kp BSI treated with a ceftazidime/avibactam-based regimen were included. Full-dose ceftazidime/avibactam (7.5 g daily) was prescribed to eighty-two patients (74.5%), while 28 patients (25.5%) received a renal-adjusted dose (17 patients due to chronic renal disease or haemodialysis, 11 patients due to infection-related acute kidney injury), with a median of 1.9 g daily. At multivariable analysis, receiving a reduced dose of ceftazidime/avibactam was independently associated with mortality (HR 4.47, 95% CI 1.09-18.03, p=0.037), along with intra-abdominal or lower respiratory tract infections as source of BSI (HR 5.42, 95% CI 1.77-16.55, p=0.003), septic shock (HR 6.99, 95% CI 1.36-35.87, p=0.020) and SARS-CoV2 coinfection (HR 10.23, 95% CI 2.69-38.85, p=0.001). Conclusions. Dose reduction of ceftazidime/avibactam according to renal function in patients with KPC-Kp BSI seems to be independently associated with higher mortality. This may be possibly due to inadequate exposure provided by the recommended doses for renal impairment.
2024
ceftazidime-avibactam; KPC-Kp; renal adjustment; renal adjusted ceftazidime-avibactam
01 Pubblicazione su rivista::01a Articolo in rivista
Impact of renal-adjusted ceftazidime/avibactam in patients with KPC-producing K. pneumoniae bloodstream infection: a retrospective cohort study / Oliva, Alessandra; Volpicelli, Lorenzo; Gigante, Antonietta; Di Nillo, Michela; Trapani, Silvia; Viscido, Agnese; Sacco, Federica; Mastroianni, Claudio. - In: JAC-ANTIMICROBIAL RESISTANCE. - ISSN 2632-1823. - (2024). [10.1093/jacamr/dlae201]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1729049
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