Concentrations in plasma and tissue penetration of ceftriaxone and ornidazole during liver transplantation

Abstract

Plasma and epiploic fat drug concentrations and fat penetration of ceftriaxone and ornidazole given for antimicrobial prophylaxis were studied in 11 patients scheduled for liver transplantation. Ceftriaxone (1 g) and ornidazole (500 mg) were infused during 30 min after the induction of anesthesia. Arterial blood and epiploic fat samples were collected at 30, 60, and 120 min and then every 90 min following the end of the infusion until closure of the peritoneum. Blood samples were immediately centrifuged, and plasma and fat were stored at -35°C until analysis. Ceftriaxone and ornidazole concentrations were determined by high-performance liquid chromatography. Surgery lasted 440 + 84 min and required a mean of 9.5 units of packed erythrocytes and 13 units of fresh frozen plasma. Plasma ceftriaxone concentrations decreased from 89 ± 34 to 41 ± 16.5 ,ag/ml from the beginning of the operation until the time of closure of the peritoneum. Corresponding levels in epiploic fat decreased from 8.7 + 3.3 to 4.5 + 3.5 ag/g. Ornidazole concentrations ranged, respectively, between 8.7 + 2.5 and 4.9 ± 1.7 ,ug/ml in plasma samples and 4.6 ± 1.2 and 2.5 _ 1.1. ,g/g in fat samples. Rates of penetration into the omentum remained at about 9%o for ceftriaxone and between 50 and 70%o for ornidazole. Tissue ceftriaxone concentrations were, in all cases, greater than typical MICs for 90%o for Escherichia coli and KlebsieUla isolates tested (MIC90s). They were insufficient in 40o of patients after 60 min with regard to the MIC90s for Staphylococcus aureus. Tissue ornidazole concentrations were not superior to MIC,0s for anaerobes after 30 min in 50%o of patients. These results show that a single dose of 1 g of ceftriaxone provides adequate coverage against gram-negative bacteria and that 1 g instead of 500 mg of ornidazole may provide a protective effect against anaerobes during liver transplantation. Prophylaxis against S. aureus and Streptococcusfaecalis requires more specific antibiotics. Prophylaxis for patients with significant blood loss or initial severe renal or hepatic failure needs further evaluation.

Ceftriaxone pharmacokinetics by new simple and sensitive ultra-high-performance liquid chromatography method

“…Bioanalytical methods for the quantification of ceftriaxone in plasma, urine, fat tissue, bones or cerebrospinal fluid with application in in vivo studies were available (Bowman et al, 1984;Gergs et al, 2014;Kratzer et al, 2014;Mcwhinney et al, 2010;Page-Sharp et al, 2016;Payasi et al, 2010;Ringger et al, 1996Ringger et al, , 1998Schleibinger et al, 2015;Steib et al, 1993;Sun et al, 2012;Verdier et al, 2011). High performance liquid chromatography (HPLC) systems with different detectors were used.…”

The need for antibiotic stewardship and treatment standardization in the care of cirrhotic patients with spontaneous bacterial peritonitis – a retrospective cohort study examining the effect of ceftriaxone dosing

“…Prospective studies in a larger cohort are indicated to explore the true significance of these results. While it could explain our results, whether the pharmacodynamics of intravenous ceftriaxone are such that the peritoneal drug concentration following a 1 g infusion results in slower control of infection is unclear from our study 19 . Third, the number, duration and complexity of antibiotic regimens that cirrhotic patients experience is highly variable.…”

Activity of Drug Combinations against Mycobacterium abscessus Grown in Aerobic and Hypoxic Conditions

“…The activity of 8 anti-Mab drugs, 9 nitro-compounds and colistin (CLS) was tested against A and H cells. The list of drugs is shown in Supplementary Table S2 [ 21 , 22 , 25 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. The drugs were purchased from Sigma-Aldrich (St. Louis, MO, USA) or Selleck Chemicals (Houston, TX, USA).…”