Superiority of ceftazidime off-label high-dose regimen in PK/PD target attainment during treatment of extensively drug-resistant Pseudomonas aeruginosa infections in cancer patients

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F23%3A10451896" target="_blank" >RIV/00179906:_____/23:10451896 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11160/23:10451896 RIV/00216208:11110/23:10451896 RIV/00216208:11150/23:10451896 RIV/00064165:_____/23:10451896

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=PNh3NpRhBq" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=PNh3NpRhBq</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/bcp.15612" target="_blank" >10.1111/bcp.15612</a>

Result language

angličtina

Original language name

Superiority of ceftazidime off-label high-dose regimen in PK/PD target attainment during treatment of extensively drug-resistant Pseudomonas aeruginosa infections in cancer patients

Original language description

Aim: The objective of this study was to evaluate off-label high-dose ceftazidime population pharmacokinetics in cancer patients with suspected or proven extensively drug-resistant (XDR) Pseudomonas aeruginosa infections and then to compare the achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target after standard and off-label high-dose regimens using population model-based simulations. A further aim was to clinically observe the occurrence of adverse effects during the off-label high-dose ceftazidime treatment. Methods: In patients treated with off-label high-dose ceftazidime (3 g every 6 h), blood samples were collected and ceftazidime serum levels measured using LC-MS/MS. A pharmacokinetic population model was developed using a nonlinear mixed-effects modelling approach and Monte Carlo simulations were then used to compare standard and high-dose regimens for PK/PD target attainment. Results: A total of 14 cancer patients with serious infection suspected of XDR P. aeruginosa aetiology were eligible for PK analysis. XDR P. aeruginosa was confirmed in 10 patients as the causative pathogen. Population ceftazidime volume of distribution was 13.23 L, while clearance started at the baseline of 1.48 L/h and increased by 0.0076 L/h with each 1 mL/min/1.73 m(2) of eGFR. High-dose regimen showed significantly higher probability of target attainment (i.e., 86% vs. 56% at MIC of 32 mg/L). This was translated into a very low mortality rate of 20%. Only one case of reversible neurological impairment was observed. Conclusion: We proved the superiority of the ceftazidime off-label high-dose regimen in PK/PD target attainment with very low occurrence of adverse effects. The off-label high-dose regimen should be used to optimize treatment of XDR P. aeruginosa infections.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

British Journal of Clinical Pharmacology

ISSN

0306-5251

e-ISSN

1365-2125

Volume of the periodical

89

Issue of the periodical within the volume

4

Country of publishing house

GB - UNITED KINGDOM

Number of pages

10

Pages from-to

1452-1461

UT code for WoS article

000894630200001

EID of the result in the Scopus database

2-s2.0-85144061988