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Therapeutic Drug Monitoring of Ceftazidime-Avibactam Concentrations in Carbapenem-Resistant K. pneumoniae-Infected
Xin-Qi Teng1, Qiang Qu2,3, Yue Luo4
1Department of Pharmacy, The Second Xiangya Hospital, Central South University, Institute of Clinical Pharmacy, Central South University, Changsha, China.
Abstract:
Aims: Carbapenem-resistant K. pneumoniae (CRKP) is the most common carbapenem-resistant Enterobacteriaceae with high mortality. Ceftazidime-avibactam (CAZ-AVI) has exhibited excellent in vitro activity in vivo against CRKP. However, the efficacy of CAZ-AVI in KPC-producing CRKP-infected patients with different kidney statuses varies, such as renal insufficiency, normal renal function, and augmented renal clearance (ARC). We explored the use of therapeutic drug monitoring (TDM) to evaluate the concentration and efficacy of CAZ-AVI in CRKP-infected patients with different kidney statuses. Methods: Serum concentrations for CAZ and AVI were determined by the high-performance liquid chromatography method. Bacterial identification, routine susceptibility testing, renal function index, and others were performed in standard protocols in the hospital's clinical laboratories. Results: In the two patients with ARC, in case 1, CAZ-AVI 2.5g q6h was used with good efficacy, and the concentrations were up to the pharmacokinetics/pharmacodynamics targets. In Case 2, 2.5 g q8h was used with invalid effectiveness, and AVI Cmin was only 0.797 mg/l, which is lower than the PK/PD target. Case 3 was renal insufficiency using CAZ-AVI 1.25 q8h, and case 4 was normal renal function using 2.5 g q8h. Their concentrations were both up to the PK/PD targets. Conclusion: TDM results demonstrated that CAZ-AVI steady-state plasma concentration varies among patients with different kidney statuses, providing evidence for the utility of TDM of CAZ-AVI in individualized drug dose adjustment. ARC patients may need more CAZ-AVI daily doses than the standard dose.
Insights
Therapeutic drug monitoring (TDM) of ceftazidime-avibactam (CAZ-AVI) helps optimize dosing for carbapenem-resistant Klebsiella pneumoniae infections. Patients with augmented renal clearance may require higher CAZ-AVI doses than standard recommendations.
Area of Science:
- Infectious Diseases
- Pharmacology
- Nephrology
Background:
- Carbapenem-resistant Klebsiella pneumoniae (CRKP) presents a significant global health threat due to high mortality rates.
- Ceftazidime-avibactam (CAZ-AVI) demonstrates potent in vitro and in vivo activity against CRKP.
- Patient kidney status, including renal insufficiency, normal function, and augmented renal clearance (ARC), influences CAZ-AVI efficacy.
Purpose of the Study:
- To evaluate the serum concentrations and clinical efficacy of CAZ-AVI in CRKP-infected patients with varying kidney functions.
- To investigate the role of therapeutic drug monitoring (TDM) in optimizing CAZ-AVI dosing for personalized treatment.
- To determine if standard CAZ-AVI doses are adequate for patients with augmented renal clearance (ARC).
Main Methods:
- Serum concentrations of ceftazidime (CAZ) and avibactam (AVI) were quantified using high-performance liquid chromatography (HPLC).
- Standard laboratory protocols were employed for bacterial identification, susceptibility testing, and assessment of renal function.
- Pharmacokinetic/pharmacodynamic (PK/PD) targets were used as benchmarks for evaluating drug concentrations.
Main Results:
- In patients with ARC, one receiving CAZ-AVI 2.5g q6h showed good efficacy and achieved PK/PD targets, while another on 2.5g q8h had sub-therapeutic AVI levels (Cmin 0.797 mg/L).
- A patient with renal insufficiency on CAZ-AVI 1.25g q8h and a patient with normal renal function on 2.5g q8h both achieved adequate drug concentrations.
- TDM revealed significant variability in CAZ-AVI steady-state plasma concentrations based on individual kidney status.
Conclusions:
- TDM is crucial for guiding individualized CAZ-AVI dosing in CRKP-infected patients, particularly those with different renal statuses.
- Patients with augmented renal clearance (ARC) may necessitate higher daily doses of CAZ-AVI than currently recommended standard doses.
- Optimized CAZ-AVI therapy through TDM can improve treatment outcomes for complex CRKP infections.
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