Therapeutic Drug Monitoring of Ceftazidime-Avibactam Concentrations in Carbapenem-Resistant K. pneumoniae-Infected Patients With Different Kidney Statuses

Teng, Xin-Qi; Qu, Qiang; Luo, Yue; Long, Wen-Ming; Zhuang, Hui; Xu, Jiao-Hua; Wen, Yu-Xin; Zhang, Huilin; Qu, Jian

doi:10.3389/fphar.2022.780991

Cited by 8 publications

(4 citation statements)

References 25 publications

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“…This phenomenon was also observed in a therapeutic drug monitoring (TDM) of CAZ-AVI concentration in CRKP-infected patients with different kidney statuses. In this study, two patients with ARC showed lower ceftazidime and avibactam serum concentrations, even though receiving 2.5 g q6 h CAZ-AVI ( Teng et al, 2022 ). These results implied that increased dosing or dose optimization using prolonged duration may be needed in ARC patients to maintain therapeutic exposure.…”

Section: Pharmacokinetic/pharmacodynamic Targets and Dosage Adjustmen...mentioning

confidence: 65%

Ceftazidime-avibactam induced renal disorders: past and present

Shi,

Wu,

et al. 2024

Front. Pharmacol.

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With the increasing prevalence of multidrug-resistant Gram-negative bacterial pathogens worldwide, antimicrobial resistance has become a significant public health concern. Ceftazidime-avibactam (CAZ-AVI) exhibited excellent in vitro activity against many carbapenemase-producing pathogens, and was widely used for the treatment of various complicated infections. CAZ-AVI is well tolerated across all dosing regimens, and its associated acute kidney injury (AKI) in phase II/III clinical trials is rare. However, recent real-world studies have demonstrated that CAZ-AVI associated AKI was more frequent in real-world than in phase II and III clinical trials, particularly in patients receiving concomitant nephrotoxic agents, with critically ill patients being at a higher risk. Herein, we reviewed the safety data related to renal impairment of CAZ-AVI, and discussed its pharmacokinetic/pharmacodynamic targets and dosage adjustment in patients with impaired renal function. This review aimed to emphasize the importance for healthcare professionals to be aware of this adverse event of CAZ-AVI and provide practical insights into the dosage optimization in critically ill patients with renal dysfunction.

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Section: Pharmacokinetic/pharmacodynamic Targets and Dosage Adjustmen...mentioning

confidence: 65%

Ceftazidime-avibactam induced renal disorders: past and present

Shi,

Wu,

et al. 2024

Front. Pharmacol.

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“… 10 However, it was confirmed that the higher the CLCr was, the lower the Css of CAZ‐AVI. In this study, CLCr >130 mL/min was used as the definition of ARC, 27 but patients with a relatively high CLCr in practice, such as 100–129 mL/min, still need to be aware of the possibility of an insufficient dosage of CAZ‐AVI. It also should be noted that the CLCr of the patient with joint PK/PD attainment before medication was 130.63 mL/min, but it dropped rapidly to 65 mL/min on the second day, resulting in a higher Css of CAZ and AVI than that of the other three patients with ARC, suggesting that the CLCr of critically ill patients may vary greatly in clinical conditions and that dynamic monitoring of CLCr and Css of CAZ‐AVI is necessary.…”

Section: Discussionmentioning

confidence: 99%

“…10 However, it was confirmed that the higher the CLCr was, the lower the Css of CAZ-AVI. In this study, CLCr >130 mL/ min was used as the definition of ARC, 27 but patients with a rela-…”

Section: Pathogenmentioning

confidence: 99%

A descriptive pharmacokinetic/pharmacodynamic analysis of ceftazidime‐avibactam in a case series of critically ill patients with augmented renal clearance

Xu,

Tang,

Yuan

et al. 2023

Pharmacology Res & Perspec

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To describe the pharmacokinetics/pharmacodynamics (PK/PD) of a 2 h infusion of ceftazidime‐avibactam (CAZ‐AVI) in critically ill patients with augmented renal clearance (ARC). A retrospective review of all critically ill patients with ARC who were treated with CAZ‐AVI between August 2020 and May 2023 was conducted. Patients whose 12‐h creatinine clearance prior to CAZ‐AVI treatment and steady‐state concentration (Css) of CAZ‐AVI were both monitored were enrolled. The free fraction (fCss) of CAZ‐AVI was calculated from Css. The joint PK/PD targets of CAZ‐AVI were considered optimal when a Css/minimum inhibitory concentration (MIC) ratio for CAZ ≥4 (equivalent to 100% fT > 4 MIC) and a Css/CT ratio of AVI >1 (equivalent to 100% fT > CT 4.0 mg/L) were reached simultaneously, quasioptimal when only one of the two targets was reached, and suboptimal when neither target was reached. The relationship between PK/PD goal achievement, microbial eradication and the clinical efficacy of CAZ‐AVI was evaluated. Four patients were included. Only one patient achieved optimal joint PK/PD targets, while the other three reached suboptimal targets. The patient with optimal PK/PD targets achieved microbiological eradication, while the other three patients did not, but all four patients achieved good clinical efficacy. Standard dosages may not enable most critically ill patients with ARC to reach the optimal joint PK/PD targets of CAZ‐AVI. Optimal drug dose adjustment of CAZ‐AVI in ARC patients requires dynamic drug concentration monitoring.

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“…Therapeutic drug monitoring (TDM) of CZA-AVI in four carbapenem-resistant K.pneumoniae -infected patients with different kidney statuses indicated that in one patient with CrCl of 194.98 ml/min/1.73m2 treated with CZA-AVI dose of 2.5 g q6h, sputum and urine cultures turned negative after 3 days. Administration of CZA-AVI (2.5 g q8h on the first day) in another subject with higher CrCl of 295.49 ml/min/1.73m2 did not improve infection, leading to the conclusion that ARC patients need higher daily doses of CAZ-AVI( Teng et al, 2022 ), suggesting that enhanced the dosing internal might be a strategy to attain the PTA Since ceftazidime and avibactam is mainly excreted through the kidney, further research is warranted to establish the impact of ARC on the clinical efficacy of CZA-AVI.…”

Section: Antibacterial Therapy In Arc Patientsmentioning

confidence: 97%

Individualized antibiotic dosage regimens for patients with augmented renal clearance

Shi

Zhuang

et al. 2023

Front. Pharmacol.

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Objectives: Augmented renal clearance (ARC) is a state of enhanced renal function commonly observed in 30%–65% of critically ill patients despite normal serum creatinine levels. Using unadjusted standard dosing regimens of renally eliminated drugs in ARC patients often leads to subtherapeutic concentrations, poor clinical outcomes, and the emergence of multidrug-resistant bacteria. We summarized pharmaceutical, pharmacokinetic, and pharmacodynamic research on the definition, underlying mechanisms, and risk factors of ARC to guide individualized dosing of antibiotics and various strategies for optimizing outcomes.Methods: We searched for articles between 2010 and 2022 in the MEDLINE database about ARC patients and antibiotics and further provided individualized antibiotic dosage regimens for patients with ARC.Results: 25 antibiotic dosage regimens for patients with ARC and various strategies for optimization of outcomes, such as extended infusion time, continuous infusion, increased dosage, and combination regimens, were summarized according to previous research.Conclusion: ARC patients, especially critically ill patients, need to make individualized adjustments to antibiotics, including dose, frequency, and method of administration. Further comprehensive research is required to determine ARC staging, expand the range of recommended antibiotics, and establish individualized dosing guidelines for ARC patients.

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Therapeutic Drug Monitoring of Ceftazidime-Avibactam Concentrations in Carbapenem-Resistant K. pneumoniae-Infected Patients With Different Kidney Statuses

Cited by 8 publications

References 25 publications

Ceftazidime-avibactam induced renal disorders: past and present

Ceftazidime-avibactam induced renal disorders: past and present

A descriptive pharmacokinetic/pharmacodynamic analysis of ceftazidime‐avibactam in a case series of critically ill patients with augmented renal clearance

Individualized antibiotic dosage regimens for patients with augmented renal clearance

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