Ceftazidime/avibactam versus standard-of-care agents against carbapenem-resistant Enterobacteriaceae harbouring blaKPC in a one-compartment pharmacokinetic/pharmacodynamic model

Barber, Katie E.; Pogue, Jason M.; Warnock, Henderson D; Kaye, Keith S.

doi:10.1093/jac/dky213

Cited by 11 publications

(4 citation statements)

References 30 publications

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“…Interestingly, we observed somewhat limited bacterial killing by CAZ/AVI in the dynamic one-compartment PK/PD model (∼2 log 10 cfu/mL reduction was observed at 48 h). Some previous studies against KPC-producing K. pneumoniae isolates in dynamic PK/PD models showed more killing than we observed in the present study (>5 log 10 cfu/mL killing by 48 h), [45] , [46] while our previous data suggest inter-isolate variations in the rate of killing exist (between 2.5 and 5 log 10 cfu/mL killing by 48 h). [47] However, isolates from the previous in vitro studies were from ST258, were not identified as hypervirulent, and they had lower MICs to CAZ/AVI ranging from 0.125/4 to 0.5/4mg/L (MICs in present study, 4/4mg/L).…”

Section: Discussioncontrasting

confidence: 49%

Ceftazidime-avibactam based combinations against carbapenemase producing Klebsiella pneumoniae harboring hypervirulence plasmids

Bulman

Tan²,

Chu³

et al. 2022

Computational and Structural Biotechnology Journal

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Section: Discussioncontrasting

confidence: 49%

Ceftazidime-avibactam based combinations against carbapenemase producing Klebsiella pneumoniae harboring hypervirulence plasmids

Bulman

Tan²,

Chu³

et al. 2022

Computational and Structural Biotechnology Journal

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“…But little work has been done to evaluate the efficacy of available antibiotics against heteroresistant strains. Ceftazidime/avibactam, a β-lactam/β-lactamase inhibitor combination, has been proposed as a new salvage therapy for severe KPC-Kp infections (Barber et al, 2018; Manning et al, 2018; Tumbarello et al, 2019). The objective of this study was to evaluate the in vitro effect of ceftazidime/avibactam in combination with polymyxin B against polymyxin B heteroresistance Klebsiella pneumoniae .…”

Section: Introductionmentioning

confidence: 99%

Ceftazidime/avibactam Improves the Antibacterial Efficacy of Polymyxin B Against Polymyxin B Heteroresistant KPC-2-Producing Klebsiella pneumoniae and Hinders Emergence of Resistant Subpopulation in vitro

et al. 2019

Front. Microbiol.

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Due to the increasing multidrug resistance and limited antibiotics, polymyxin B revived as the last resort for the treatment of carbapenemase-producing Klebsiella pneumoniae (CRKP). Unfortunately, the heteroresistance hampers polymyxin B monotherapy treatment via the amplification of resistant subpopulation. Reliable polymyxin B based combinations are demanded. Ceftazidime/avibactam has been regarded as a new salvage therapy against CRKP. The occurrence of heteroresistance was confirmed by population analysis profiling (PAP). Our study demonstrated that polymyxin B and ceftazidime/avibactam combinations improved the in vitro antimicrobial activity of polymyxin B and delayed or suppressed the regrowth of resistant subpopulation by time-kill studies. Ceftazidime/avibactam at around MIC values (0.5–1 × MIC) plus clinically achievable concentrations of polymyxin B (0.5–2 mg/L) resulted in sustained killing against polymyxin B-heteroresistant isolates. Active PmrAB and PhoPQ systems and a pmrA mutation (G53R) in resistant subpopulation might associate with heteroresistance, but further investigation was required. Our findings suggested that the heteroresistance represented barriers to polymyxin B efficacy, and the combination of polymyxin B with ceftazidime/avibactam could be potentially valuable for the treatment of heteroresistant CRKP. Further, in vivo studies need to be performed to evaluate the efficacy of this combination against heteroresistant strains.

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“…Given that both CAZ and AVI are less than 10% bound to plasma proteins, the total concentrations measured were approximated as free concentrations. As the one‐compartment model could perfectly describe the process of distribution and linear elimination for CAZ and AVI in the body, 27,28 t 1/2 and % fT in patients could be calculated based on the C trough and C peak . The optimal PK/PD targets for CAZ and AVI are 50% fT > MIC and 50% fT > C T of 1 mg/L, respectively.…”

Section: Discussionmentioning

confidence: 99%

Rapid, simple, and economical LC–MS/MS method for simultaneous determination of ceftazidime and avibactam in human plasma and its application in therapeutic drug monitoring

Cheng

Chen

Zhang

et al. 2022

Clinical Pharmacy Therapeu

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What is Known and Objective: Carbapenem-resistant Gram-negative bacterial pathogens continue to threaten public health. Avibactam (AVI), a novel non-β-lactam β-lactamase inhibitor, has been approved for use with ceftazidime (CAZ) mainly against carbapenem-resistant Enterobacteriaceae. Therapeutic drug monitoring (TDM) is urgently needed to optimize dosage regimens to maximize efficacy, minimize toxicity, and delay the emergence of resistance. This study aims to develop and validate a rapid, simple, and economical LC-MS/MS method for simultaneous determination of CAZ/AVI in human plasma.Methods: Samples were processed by simple protein precipitation, and gradient elution strategy was applied to separate CAZ and AVI on a reverse-phase C18 column; with subsequent detection by the mass spectrometer in a positive and negative ion switching mode. Plasma samples from patients were analysed.Results and Discussion: A 4-min run of LC-MS/MS was developed. The precision, trueness, matrix effect, extraction recovery, carry-over, dilution integrity, and stability were all acceptable for a bioanalytical method. The method was successfully applied to the determination of CAZ and AVI in patients, and a considerable PK variability of CAZ/AVI was observed among patients.What is New and Conclusion: A robust, rapid, simple, and economical LC-MS/MS method for the simultaneous determination of CAZ and AVI was developed. The considerable PK variability of CAZ/AVI among patients demonstrates the clinical significance of TDM.

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Ceftazidime/avibactam versus standard-of-care agents against carbapenem-resistant Enterobacteriaceae harbouring blaKPC in a one-compartment pharmacokinetic/pharmacodynamic model

Cited by 11 publications

References 30 publications

Ceftazidime-avibactam based combinations against carbapenemase producing Klebsiella pneumoniae harboring hypervirulence plasmids

Ceftazidime-avibactam based combinations against carbapenemase producing Klebsiella pneumoniae harboring hypervirulence plasmids

Ceftazidime/avibactam Improves the Antibacterial Efficacy of Polymyxin B Against Polymyxin B Heteroresistant KPC-2-Producing Klebsiella pneumoniae and Hinders Emergence of Resistant Subpopulation in vitro

Rapid, simple, and economical LC–MS/MS method for simultaneous determination of ceftazidime and avibactam in human plasma and its application in therapeutic drug monitoring

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