Effects of cardiopulmonary bypass on the disposition of cefazolin in patients undergoing cardiothoracic surgery

Asada, Mizuho; Nagata, Masashi; Mizuno, Tomohiro; Uchida, Tatsuo; Kurashima, Naoki; Takahashi, Hiromitsu; Makita, Koshi; Arai, Hirokuni; Echizen, Hirotoshi; Yasuhara, Masato

doi:10.1002/prp2.440

Cited by 10 publications

(6 citation statements)

References 29 publications

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“…A low level of serum albumin is expected to result in a lower protein binding. Correlations between the albumin concentrations and protein binding were seen for cefazolin, ceftizoxime, ceftriaxone, and cefoperazone ( Ohashi et al, 1986 ; Fortunato et al, 1993 ; Allegaert et al, 2009 ; Himebauch et al, 2014 ; Schleibinger et al, 2015 ; de Cock et al, 2017 ; Asada et al, 2018 ; Kan et al, 2020 ; Booke et al, 2021 ; Hartman et al, 2021 ). However, the studies of Toth et al (1991) and Tsai et al (2016) showed no correlation between the albumin concentration and the protein binding of ceftriaxone.…”

Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

“…Cardiopulmonary bypass (CPB) led to differences in protein binding during the procedure ( Hollis et al, 2015 ; de Cock et al, 2017 ; Asada et al, 2018 ). Cefazolin protein binding was shown to be low (53%–55%) during CBP ( Hollis et al, 2015 ; Asada et al, 2018 ). One study compared the binding during CBP with the binding preoperative in the same group of patients and found different values of 55% during CBP and 79% pre-CBP ( Asada et al, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

“…Cefazolin protein binding was shown to be low (53%–55%) during CBP ( Hollis et al, 2015 ; Asada et al, 2018 ). One study compared the binding during CBP with the binding preoperative in the same group of patients and found different values of 55% during CBP and 79% pre-CBP ( Asada et al, 2018 ). For cefuroxime the data were not consistent.…”

Section: Resultsmentioning

confidence: 99%

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An Overview of the Protein Binding of Cephalosporins in Human Body Fluids: A Systematic Review

Jongmans

Muller²,

Broek³

et al. 2022

Front. Pharmacol.

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Introduction: Protein binding can diminish the pharmacological effect of beta-lactam antibiotics. Only the free fraction has an antibacterial effect. The aim of this systematic literature review was to give an overview of the current knowledge of protein binding of cephalosporins in human body fluids as well as to describe patient characteristics influencing the level of protein binding.Method: A systematic literature search was performed in Embase, Medline ALL, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials with the following search terms: “protein binding,” “beta-lactam antibiotic,” and “body fluid.” Only studies were included where protein binding was measured in humans in vivo.Results: The majority of studies reporting protein binding were performed in serum or plasma. Other fluids included pericardial fluid, blister fluid, bronchial secretion, pleural exudate, wound exudate, cerebrospinal fluid, dialysate, and peritoneal fluid. Protein binding differs between diverse cephalosporins and between different patient categories. For cefazolin, ceftriaxone, cefpiramide, and cefonicid a non-linear pattern in protein binding in serum or plasma was described. Several patient characteristics were associated with low serum albumin concentrations and were found to have lower protein binding compared to healthy volunteers. This was for critically ill patients, dialysis patients, and patients undergoing cardiopulmonary bypass during surgery. While mean/median percentages of protein binding are lower in these patient groups, individual values may vary considerably. Age is not likely to influence protein binding by itself, however limited data suggest that lower protein binding in newborns. Obesity was not correlated with altered protein binding.Discussion/Conclusion: Conclusions on protein binding in other body fluids than blood cannot be drawn due to the scarcity of data. In serum and plasma, there is a large variability in protein binding per cephalosporin and between different categories of patients. Several characteristics were identified which lead to a lower protein binding. The finding that some of the cephalosporins display a non-linear pattern of protein binding makes it even more difficult to predict the unbound concentrations in individual patients. Taken all these factors, it is recommended to measure unbound concentrations to optimize antibiotic exposure in individual patients.Systematic Review Registration: PROSPERO, identifier (CRD42021252776).

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

An Overview of the Protein Binding of Cephalosporins in Human Body Fluids: A Systematic Review

Jongmans

Muller²,

Broek³

et al. 2022

Front. Pharmacol.

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show abstract

“…In this study, the within‐day and between‐day variations (<15% at each concentration and <20% at the lowest concentration) were within the recommended guidelines (Table 1) of the US Food and Drug Administration, 2001). In addition, the preparation procedure for the 10‐fold dilution was simpler and faster than previous assays using blood samples (Asada et al, 2018). Moreover, the developed method determines the urinary cefazolin concentration within a short time (5 min), which is comparable with previously reported methods such as the HPLC–UV method (Kamani et al, 1998; Martinez et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Simple determination of urine cefazolin concentration in pediatric patients with urinary tract infections using high‐performance liquid chromatography

Abe

Momo

Abe

et al. 2022

Biomedical Chromatography

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Recently, global health concerns regarding increasing multidrug resistance have arisen. This study aimed to develop a simple, inexpensive and rapid high-performance liquid chromatography-ultraviolet (HPLC-UV) method for determining urinary concentrations of a first-generation cephem antibiotic in pediatric patients with urinary tract infections (UTIs). HPLC-UV was used to analyze urinary cefazolin concentrations at a detection wavelength of 254 nm. The assay used contained 10-fold diluted urine with an internal standard (cephapirin). The standard calibration curve for cefazolin was linear in the concentration range of 31.25-500 μg/ml (r 2 > 0.999). The retention times of cefazolin and the internal standard were 4.2 and 4.9 min, respectively. The within-and between-day coefficients of variation were in the concentration ranges 1.2-15.2 and 5.5-19.2%, respectively. The urinary cefazolin concentration of a pediatric patient with a UTI was 1,476.6 μg/ml, which was over 700-fold higher than the minimum inhibitory concentration of cefazolin (≤2 μg/ml).The developed method is applicable to the confirmation of appropriate use for UTI treatment as therapeutic drug monitoring of cefazolin. Therefore, the findings of this study may contribute to the appropriate use of antibiotics to prevent antimicrobial resistance in pediatric patients with UTIs.

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Dose optimization of cefazolin in South African children undergoing cardiac surgery with cardiopulmonary bypass

Gebreyesus,

Dresner,

Wiesner

et al. 2024

CPT Pharmacom & Syst Pharma

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Cefazolin is an antibiotic used to prevent surgical site infections. During cardiac surgery with cardiopulmonary bypass (CPB), its efficacy target could be underachieved. We aimed to develop a population pharmacokinetic model for cefazolin in children and optimize the prophylactic dosing regimen. Children under 25 kg undergoing cardiac surgery with CPB and receiving cefazolin at standard doses (50 mg/kg IV every 4–6 h) were included in this analysis. A population pharmacokinetic model and Monte Carlo simulations were used to evaluate the probability of target attainment (PTA) for efficacy and toxicity with the standard regimen and an alternative regimen of continuous infusion, where loading and maintenance doses were calculated from model‐derived individual parameters. Twenty‐two patients were included, with median (range) age, body weight, and eGFR of 19.5 (1–94) months, 8.7 (2–21) kg, and 116 (48–159) mL/min, respectively. Six patients received an additional dose in the CPB circuit. A two‐compartment disposition model with an additional compartment for the CPB was developed, including weight‐based allometric scaling and eGFR. For a 10 kg patient with eGFR of 120 mL/min/1.73 m2, clearance was estimated as 0.856 L/h. Simulations indicated that the standard dosing regimen fell short of achieving the efficacy target >40% of the time within a dosing duration and in patients with good renal function, PTA ranged from <20% to 70% for the smallest to the largest patients, respectively, at high MICs. In contrast, the alternative regimen consistently maintained target concentrations throughout the procedure for all patients while using a lower overall dose.

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Effects of cardiopulmonary bypass on the disposition of cefazolin in patients undergoing cardiothoracic surgery

Cited by 10 publications

References 29 publications

An Overview of the Protein Binding of Cephalosporins in Human Body Fluids: A Systematic Review

An Overview of the Protein Binding of Cephalosporins in Human Body Fluids: A Systematic Review

Simple determination of urine cefazolin concentration in pediatric patients with urinary tract infections using high‐performance liquid chromatography

Dose optimization of cefazolin in South African children undergoing cardiac surgery with cardiopulmonary bypass

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