Biliary pharmacokinetic/pharmacodynamic analysis of continuous infusion ceftazidime-avibactam in a case series of orthotopic liver transplant recipients
Abstract
OBJECTIVES: To assess the biliary pharmacokinetic/pharmacodynamic (PK/PD) of continuous infusion (CI) ceftazidime-avibactam in a series of critical orthotopic liver transplant (OLT) recipients having pre-emptive therapy during OLT because of carbapenemase-producing Enterobacterales (CPE) rectal colonization or targeted therapy of CPE intra-abdominal (IAIs) and/or biliary tract infections (BTIs).
METHODS: We performed an exploratory, hypothesis-generating prospective case series including critical OLT recipients carrying a Kehr's tube and undergoing therapeutic drug monitoring of ceftazidime and avibactam in both bile and plasma simultaneously while receiving CI ceftazidime-avibactam pre-emptive or targeted therapy. Biliary aggressive joint PK/PD target attainment [defined as a free ceftazidime steady-state concentrations fCss/MIC ratio >4 coupled with an avibactam fCss/target concentration (CT = 4 mg/L) ratio >1] was selected as optimal threshold of ceftazidime-avibactam efficacy, given this was previously shown to be independently associated with lower rates of microbiological failure and resistance development. Bile-to-plasma fCss ratios were calculated.
RESULTS: Overall, four critical OLT recipients were included. Aggressive biliary ceftazidime-avibactam joint PK/PD target during treatment with CI 2 g/0.5 g q8 h over 8 h was attained in 2/4 cases (quasi-optimal and suboptimal in one case each). Median (range) fCss bile-to-plasma ratios were 0.28 (0.22-0.38) for…
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Evidence Hub reads this as a case series, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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