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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.