Pharmacokinetics and Pharmacodynamics of Antimicrobials in Critically Ill Patients

Owen, Emily; Gibson, Gabrielle; Buckman, Sara

doi:10.1089/sur.2017.262

Cited by 10 publications

(7 citation statements)

References 56 publications

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“…The present study showed that the standard dosing of LNZ (600 mg q12h) for all patients led to subtherapeutic LNZ exposure in critically ill Chinese patients. The high variability and outside-the-target ranges of LNZ levels were in line with those in other studies on Caucasian patients [8,[20][21][22][23]. In this study, CrCL was identi ed as the most important covariate on the LNZ clearance, which is a comprehensive indicator including body weight, age, serum creatinine, and sex.…”

Section: Discussionsupporting

confidence: 83%

“…Patients enrolled before October 30, 2018, were included in the model establishment group, and those enrolled after were included in the external validation group. The study protocol was designed according to the SPIRIT guideline [20]. All experiments were performed under the approved protocols, guidelines, and regulations, and all patients (or appropriate surrogates for patients unable to consent) provided written informed consent simultaneously.…”

Section: Study Design and Patientsmentioning

confidence: 99%

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Pharmacokinetic of linezolid dose adjustment for creatinine clearance in critically ill patients: a multicenter, prospective, open-label, observational study

Wang

Yao

et al. 2020

Preprint

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BackgroundLinezolid (LNZ) is a common antibiotic used to treat bacterial infections. But there is a lack of evaluation of pharmacokinetics (PK) of LNZ dose adjustment for creatinine clearance (CrCL) in highly heterogeneous critically ill patients. By using a population PK approach, we aimed to determine the optimal dosing strategy for LNZ in critically ill patients, especially those along with renal dysfunction. MethodsThis multicenter, prospective, open-label, observational study was conducted in intensive care units of 4 tertiary hospitals. Of the 152 eligible patients, 117 were included for establishing the PK model. Besides internal validation, external validation was conducted using another 35 patients as a validation group. The area under curve from 0 to 24h at steady-state divided by the minimum inhibitory concentration (AUC24/MIC) >80 and trough concentration of LNZ <10 mg/L was used as the target pharmacodynamic index. Dosing regimens for MIC of 0.5 to 4 mg/L were evaluated based on low, normal, and high creatinine clearance using Monte Carlo simulation.ResultsA one-compartment model was chosen as the base model. The PK parameter estimates were clearance of 5.60 L/h and the volume of the central compartment of 43.4 L. CrCL had a significant influence on clearance of LNZ, with an adjusting factor of 0.386. The standard dosing regimen [600 mg every 12 hour (q12h)] achieved adequate exposure in patients with severe renal impairment (CrCL, 40 mL/min). A daily dose of 1200 mg could provide sufficient exposure for MIC less than 2 mg/L in patients with normal renal functions (CrCL, 80 mL/min). For augmented renal clearance (ARC), a daily dose of 1200 mg could provide sufficient exposure for MIC less than 2 mg/L. Continuous infusion obtained a similar clinical response.ConclusionsFor critically ill patients, the standard dose of 600 mg LNZ q12h was adequate for MIC<1 mg/L. With ARC, a 1200 or 1800 mg/day 24h continuous infusion was recommended.

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Section: Discussionsupporting

confidence: 83%

Section: Study Design and Patientsmentioning

confidence: 99%

Pharmacokinetic of linezolid dose adjustment for creatinine clearance in critically ill patients: a multicenter, prospective, open-label, observational study

Wang

Yao

et al. 2020

Preprint

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“…anti-infective drugs' PK parameters are commonly known to be influenced by multiple patient-related factors as well as some interferential supportive therapy. 25 For these reasons, we studied the The mortality rate (Table 2) in our study (1.2%) was lower than that found in other studies (4.1%). 20 Caspofungin prophylaxis and therapy were effective in 94.96% (132/139) and 80% (20/25), respectively ( For caspofungin, drug-drug interactions caused by enzyme inducers as well as some immunosuppressants have already been F I G U R E 4 Caspofungin trough concentrations under different conditions (weight ≤70 kg and weight ≥70 kg; with continuous renal replacement therapy (CRRT) before transplantation and without CRRT; with cyclosporine A and without cyclosporine A therapy; ALB ≤30 g/L and ALB ≥30 g/L).…”

Section: Discussioncontrasting

confidence: 47%

“…At present, no available studies support the use of echinocandins for prophylaxis among kidney transplant patients . Furthermore, anti‐infective drugs' PK parameters are commonly known to be influenced by multiple patient‐related factors as well as some interferential supportive therapy . For these reasons, we studied the efficacy and safety of caspofungin treatment and prophylaxis in the kidney transplant patients and evaluated the factors influencing caspofungin C min in kidney transplant patients.…”

Section: Discussionmentioning

confidence: 99%

Factors influencing caspofungin plasma concentrations in kidney transplant patients with high incidence of invasive fungal infections

et al. 2019

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What is known and objective: Caspofungin is commonly used in kidney transplant patients for prophylaxis or treatment of invasive fungal infections (IFIs) caused by Candida spp. and Aspergillus spp. Factors such as concomitant medications, co-morbidity and rejection often cause caspofungin pharmacokinetic parameters alterations in kidney transplant patients. Here, we aimed to investigate factors influencing caspofungin plasma concentrations and evaluate its prophylaxis and treatment efficiency for IFIs in kidney transplant patients. Methods: The prophylaxis and treatment efficiency of caspofungin for IFIs were assessed in 164 kidney transplant patients in the study. Six hundred and fifty-two caspofungin trough concentrations (C min) from the 164 patients were monitored by the liquid chromatography-tandem mass spectrometry method. Basic demographic variables, baseline disease, surgery, rejection, indwelling catheter, coinfection, concomitant medication and other caspofungin-related factors were collected. Univariate and multivariate analyses were used to assess factors influencing caspofungin plasma concentrations. Results and discussion: The success rates were 94.96% (132/139) for caspofungin prevention and 80% (20/25) for caspofungin for IFIs. Caspofungin C min in the kidney recipients varied largely compared with healthy volunteers (0.10-12.25 mg/L vs. 1.12-1.78 mg/L). Caspofungin C min significantly increased in patients with continuous renal replacement therapy before transplantation (P = .001), concomitant medication of cyclosporine A (CsA, P = .009), ALB concentration of > 30 g/L (P = .019). What is new and conclusion: This is an uncontrolled observational study of caspofungin as prophylaxis or treatment for IFIs in kidney transplant patients. Caspofungin could be an effective and well-tolerated option for antifungal prophylaxis and treatment in kidney transplant patients, and a number of factors could influence caspofungin C min in these patients. K E Y W O R D S drug monitoring, invasive fungal infections, plasma concentrations, prophylaxis, transplant patients | 73 YAN et Al. How to cite this article: Yang Q, Zhang T, Zhao D, et al. Factors influencing caspofungin plasma concentrations in kidney transplant patients with high incidence of invasive fungal infections.

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“…The study protocol was planned in accordance with the SPIRIT guideline. 20 All experiments were conducted in compliance with the approved protocols, guidelines, and regulations, and all patients (or suitable surrogates for patients unable to consent) provided written informed consent. This study was approved by the Ethics Committee of Guangdong Provincial People’s Hospital, Nanfang Hospital, Guangzhou First People’s Hospital, and Guangzhou 999 Brain Hospital (Guangdong, China) (GDREC2018269H(R1)) and was carried out in compliance with the Declaration of Helsinki.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of Linezolid Dose Adjustment for Creatinine Clearance in Critically Ill Patients: A Multicenter, Prospective, Open-Label, Observational Study

Wang¹,

Wang²,

Yao³

et al. 2021

DDDT

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The aim of this study is to use a population pharmacokinetic (PK) approach to evaluate the optimal dosing strategy for linezolid (LNZ) in critically ill patients. Methods: This multicenter, prospective, open-label, observational study was conducted in 152 patients, and 117 of them were included in the PK model, whereas the rest were in the validation group. The percentage of therapeutic target attainment (PTTA) comprising two pharmacodynamic indices and one toxicity index was used to evaluate dosing regimens based on Monte Carlo simulations stratified by low, normal, and high renal clearance for MICs of 0.25-4 mg/L. Results: A single-compartment model with a covariate creatinine clearance (CrCL) was chosen as the final model. The PK parameter estimates were clearance of 5.60 L/h, with CrCL adjustment factor of 0.386, and a distribution volume of 43.4 L. For MIC ≤2 mg/L, the standard dosing regimen (600 mg q12h) for patients with severe renal impairment (CrCL, 40 mL/min) and standard dosing or 900 mg q12h for patients with normal renal functions (CrCL, 80 mL/min) could achieve PTTA ≥74%. The dose of 2400 mg per 24-h continuous infusion was ideal for augmented renal clearance (ARC) with MIC ≤1 mg/L. For MICs >2 mg/L, rare optimal dose regimens were found regardless of renal function. Conclusion:In critically ill patients, the standard dose of 600 mg q12h was sufficient for MIC ≤2 mg/L in patients without ARC. Moreover, a 2400 mg/day 24-h continuous infusion was recommended for ARC patients.

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Pharmacokinetics and Pharmacodynamics of Antimicrobials in Critically Ill Patients

Cited by 10 publications

References 56 publications

Pharmacokinetic of linezolid dose adjustment for creatinine clearance in critically ill patients: a multicenter, prospective, open-label, observational study

Pharmacokinetic of linezolid dose adjustment for creatinine clearance in critically ill patients: a multicenter, prospective, open-label, observational study

Factors influencing caspofungin plasma concentrations in kidney transplant patients with high incidence of invasive fungal infections

Pharmacokinetics of Linezolid Dose Adjustment for Creatinine Clearance in Critically Ill Patients: A Multicenter, Prospective, Open-Label, Observational Study

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