Tigecycline Dosing Strategies in Critically Ill Liver-Impaired Patients

Amann, Lisa F; Alraish, Rawan; Broeker, Astrid; Kaffarnik, Magnus; Wicha, Sebastian G.

doi:10.3390/antibiotics11040479

Cited by 3 publications

(10 citation statements)

References 37 publications

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“…According to Child-Pugh Score (CPS) classification, there were seven cases with CPSc, five with CPS B , and nine with CPS A . 20 Pulmonary diseases (80/203, 39.41%) ranked the third. The rate of admission to intensive care unit was 73.89% (150/203).…”

Section: Resultsmentioning

confidence: 99%

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Evaluation of Tigecycline Utilization and Trends in Antibacterial Resistance from 2018 to 2021 in a Comprehensive Teaching Hospital in China

Zhou¹,

Sun²,

Lyu³

et al. 2023

IDR

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Purpose Tigecycline, the first glycylcycline antibiotic, which was widely used for off-label indications because of its broad-spectrum antibacterial activity. This study evaluated the indications for clinical use of tigecycline, clinical and microbiological effectiveness, factors associated with in hospital mortality, and bacterial resistance. Methods This retrospective study evaluated all inpatients who received tigecycline treatment for >72 hours between January 2018 and December 2021 in a comprehensive teaching hospital in China. The evaluation included indications, administration regimen, etiology, efficacy and so on. Univariate and multivariate analyses were used to evaluate the risk factors for all-cause mortality. Results There were 203 patients treated with tigecycline. Tigecycline was commonly prescribed for off-label indications (83.25%, 169/203), and hospital-acquired pneumonia ranked first (79.29%, 134/169). The most common pathogen was Acinetobacter baumannii . Clinical and microbiological success was 57.14% (116/203) and 32.28% (41/127), respectively. Fifty-four patients died and all-cause mortality was 26.60%. Univariate and multivariate analyses showed no significant difference in age, gender, off-label indication, duration of treatment, combination with other drugs, multidrug-resistant or extensively drug-resistant infections and tigecycline application scoring with respect to mortality. Conclusion Although detection of A. baumannii has decreased in the past 4 years in our hospital, resistance to tigecycline has increased. For clinical application, physicians attach importance to detection of pathogenic microorganisms, but there is still empirical medication without bacterial culture reports. Therefore, an antibiotic stewardship program oriented toward tigecycline should be strengthened to curb bacterial resistance.

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Section: Resultsmentioning

confidence: 99%

“…Followed by liver-related diseases (93/203, 45.81%). According to Child-Pugh Score (CPS) classification, there were seven cases with CPSc, five with CPS B , and nine with CPS A 20. Pulmonary diseases (80/203, 39.41%) ranked the third.…”

mentioning

confidence: 99%

Evaluation of Tigecycline Utilization and Trends in Antibacterial Resistance from 2018 to 2021 in a Comprehensive Teaching Hospital in China

Zhou¹,

Sun²,

Lyu³

et al. 2023

IDR

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“…Most of the published population pharmacokinetic (PPK) studies on tigecycline were conducted in special subpopulations (e.g., patients with intra-abdominal infections, hospital-acquired pneumonia, sepsis or septic shock, as well as patients with decompensated cirrhosis and severe infections, etc. ), while only two studies with limited sampling were carried out on critically ill patients ( Wart et al, 2006 ; Rubino et al, 2010 ; Xie et al, 2017 ; Broeker et al, 2018 ; Moor et al, 2018 ; Yang et al, 2021 ; Zhou et al, 2021 ; Amann et al, 2022 ; Bastida et al, 2022 ; Luo et al, 2023 ). On the other hand, although the recommended dose of tigecycline in drug labels appears to be straightforward (an initial dose of 100 mg followed by 50 mg every 12 h for 5–14 days), increasing evidence shows that the common dose may result in higher all-cause mortality, whereas a high-dose tigecycline therapy strategy (an initial dose of 200 mg followed by 100 mg every 12 h) may have higher clinical cure rate ( McGovern et al, 2013 ; Xie et al, 2014 ; Zha et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Population pharmacokinetics and individualized dosing of tigecycline for critically ill patients: a prospective study with intensive sampling

Su,

Song,

Liu

et al. 2024

Front. Pharmacol.

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Background: Due to the heterogeneity of critically ill patients, the pharmacokinetics of tigecycline are unclear, and the optimal dosing strategy is controversial.Methods: A single-center prospective clinical study that included critically ill patients who received tigecycline was performed. Blood samples were intensively sampled (eight samples each), and plasma drug concentrations were determined. A population pharmacokinetic (PPK) model was developed and evaluated by goodness-of-fit plots, bootstrap analysis and visual predictive checks. Monte Carlo simulation was conducted to optimize the dosage regimen.Results: Overall, 751 observations from 98 patients were included. The final PPK model was a two-compartment model incorporating covariates of creatinine clearance on clearance (CL), body weight on both central and peripheral volumes of distribution (V1 and V2), γ-glutamyl transferase and total bilirubin on intercompartment clearance (Q), and albumin on V2. The typical values of CL, Q, V1 and V2 were 3.09 L/h, 39.7 L/h, 32.1 L and 113 L, respectively. A dosage regimen of 50 mg/12 h was suitable for complicated intra-abdominal infections, but 100 mg/12 h was needed for community-acquired pneumonia, skin and skin structure infections and infections caused by less-susceptive bacteria.Conclusion: The Tigecycline PPK model was successfully developed and validated. Individualized dosing of tigecycline could be beneficial for critically ill patients.

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“…With increasing resistance to firstline antibiotics, tigecycline is often one of the few ultimate alternatives to treat severe infections. [1][2][3] Hepatic dysfunction decreases plasma protein concentrations and changes in the synthesis and transport of bile acids, which alters the distribution and elimination of the drug and affects pharmacokinetic parameters. 4 Tigecycline is excreted from the body primarily through biliary excretion in the feces (59%) and urine (22%), and approximately 20% tigecycline is metabolized by the liver.…”

Section: Introductionmentioning

confidence: 99%

“…With increasing resistance to first-line antibiotics, tigecycline is often one of the few ultimate alternatives to treat severe infections. 1–3…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Target Attainment of Tigecycline in Patients with Hepatic Impairment in a Real-World Setting

Yang¹,

Jin²,

Luo³

et al. 2023

Therapeutic Drug Monitoring

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Background: This study aimed to investigate the pharmacokinetic/ pharmacodynamic (PK/PD) target attainment of various tigecycline dosing regimens in real-world patients with impaired liver function. Methods:The clinical data and serum concentrations of tigecycline were extracted from the patients' electronic medical records. Patients were classified into Child-Pugh A, Child-Pugh B, and Child-Pugh C groups, according to the severity of liver impairment. Furthermore, the minimum inhibition concentration (MIC) distribution and PK/PD targets of tigecycline from the literature were used to obtain a proportion of PK/PD targets attainment of various tigecycline dosing regimens at different infected sites. Results:The pharmacokinetic parameters revealed significantly higher values in moderate and severe liver failure (groups Child-Pugh B and Child-Pugh C) than those in mild impairment (Child-Pugh A). Considering the target area under the time-concentration curve (AUC 0-24 )/MIC $4.5 for patients with pulmonary infection, most patients with high-dose (100 mg, every 12 hours) or standarddose (50 mg, every 12 hours) for tigecycline achieved the target in groups Child-Pugh A, B, and C. Considering the target AUC 0-24 / MIC $6.96 for patients with intra-abdominal infection, when MIC #1 mg/L, more than 80% of the patients achieved the target. For an MIC of 2-4 mg/L, only patients with high-dose tigecycline in groups Child-Pugh B and C attained the treatment target. Patients experienced a reduction in fibrinogen values after treatment with tigecycline. In group Child-Pugh C, all 6 patients developed hypofibrinogenemia.Conclusions: Severe hepatic impairment may attain higher PK/PD targets, but carries a high risk of adverse reactions.

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Tigecycline Dosing Strategies in Critically Ill Liver-Impaired Patients

Cited by 3 publications

References 37 publications

Evaluation of Tigecycline Utilization and Trends in Antibacterial Resistance from 2018 to 2021 in a Comprehensive Teaching Hospital in China

Evaluation of Tigecycline Utilization and Trends in Antibacterial Resistance from 2018 to 2021 in a Comprehensive Teaching Hospital in China

Population pharmacokinetics and individualized dosing of tigecycline for critically ill patients: a prospective study with intensive sampling

Pharmacokinetic/Pharmacodynamic Target Attainment of Tigecycline in Patients with Hepatic Impairment in a Real-World Setting

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