Cefoperazone/sulbactam therapeutic drug monitoring in patients with liver cirrhosis: Potential factors affecting the pharmacokinetic/pharmacodynamic target attainment

Abstract

Objectives Cefoperazone/sulbactam trough concentration (Cmin) varies widely in cirrhotic patients. The objective of this study was to describe the characteristics of Cmin and to identify factors associated with the pharmacokinetic/pharmacodynamic (PK/PD) target attainment of cefoperazone/sulbactam in cirrhotic patients. Methods Data were collected retrospectively from cirrhotic patients who received cefoperazone/sulbactam treatment. The Cmin was measured using a validated liquid chromatography‐tandem mass spectrometry. The PK/PD target of 100% fT > MIC was used for cefoperazone/sulbactam. Multivariate logistic regression and classification and regression tree (CART) analysis were performed to identify the factors affecting the PK/PD target attainment in these patients. Results Cefoperazone and sulbactam Cmin were measured simultaneously in 103 plasma samples from 70 cirrhotic patients. Cefoperazone and sulbactam Cmin were 89.27 ± 44.38 mg/L and 10.09 ± 13.01 mg/L, respectively. The PK/PD target of 100% fT > MIC was achieved in 47.1% (33/70) patients for cefoperazone and in 28.6% (20/70) patients for sulbactam. The CART analysis revealed that cefoperazone Cmin was likely to reach the PK/PD target in patients with serum bilirubin levels between 26.15 μmol/L and 99.15 μmol/L. Inversely, lower cefoperazone Cmin was observed in patients with bilirubin levels ≤26.15 μmol/L and serum albumin >38.45 g/L or in patients with bilirubin levels >99.15 μmol/L and creatinine clearance (CrCl) >139.13 mL/min. Additionally, patients had higher sulbactam Cmin when CrCl was below 62.85 mL/min. Conclusions This study shows that current cefoperazone/sulbactam dosage regimens may result in inadequate plasma concentrations in cirrhotic patients. We recommend monitoring the Cmin of cefoperazone/sulbactam to ensure efficacy of cefoperazone/sulbactam treatment.

The Investigation on Nosocomial Infection of Acinetobacter baumannii and the Clinical Analysis of Sequential Therapy of Cefoperazone/Sulbactam Sodium for Intracranial Infection

“…This is because tigecycline can play an antibacterial role by binding to the 30S subunit of bacterial ribosome and inhibiting bacterial protein synthesis [ 19 ], and cefoperazone can exert its antibacterial effect by inhibiting bacterial cell wall synthesis. Although sulbactam sodium itself has no antibacterial effect, it has an irreversible inhibitory effect on the production of β -lactamase by gram-negative bacilli, reducing its effect on the efficacy of cephalosporin antibiotics [ 20 ]. In general, the three-drug components can exert synergistic effects through different pathways to better control intracranial infection.…”

A retrospective cohort study of coagulation function in patients with liver cirrhosis receiving cefoperazone/sulbactam with and without vitamin K1 supplementation

“…This suggests that sulbactam may intensify cefoperazone's effect on coagulation function [7]. A study on the PK/PD of cefoperazone/sulbactam in cirrhotic patients showed that the total clearance of cefoperazone was often decreased in cirrhotic patients [10], which would theoretically exacerbate vitamin K1 de ciency. Based on this pathogenic mechanism, vitamin K1 supplementation has been suggested as a resolution [18].…”

“…Patients with cirrhosis face an infection rate of 32-34%. Cefoperazone/sulbactam is recommended as the initial empirical treatment regimen for cirrhotic patients with infections [9][10]. However, the risk of coagulopathy may be underestimated.…”

Safety and efficacy of non-reduced use of caspofungin in patients with Child–Pugh B or C cirrhosis: a real-world study

“…Similarly, a therapeutic drug monitoring study of cefoperazone/sulbactam, also a highly protein bound drug with cefoperazone primarily excreted through bile and 20–30% renal excretion, conducted in 70 cirrhotic patients has also observed that varied serum total bilirubin levels exerted differential effects on drug clearance. Specifically, lower trough concentration ( C min ) of cefoperazone was observed in patients with bilirubin levels at both lower and higher extremes (≤ 26.15 μmol/L and > 99.15 μmol/L), while patients with mid-range bilirubin levels (26.15–99.15 μmol/L) were more likely to achieve the pharmacokinetic/pharmacodynamic target [ 16 ]. It might be due to patients with normal bilirubin levels tend to have no or only mild hepatic dysfunction, whereas excessively elevated serum bilirubin may cause a greater proportion of unbound drug concentration through competitive binding to plasma albumin with highly protein bound drugs [ 17 ].…”