Universität zu Köln

Scharf, Christina, Liebchen, Uwe, Paal, Michael, Taubert, Max, Vogeser, Michael, Irlbeck, Michael, Zoller, Michael and Schroeder, Ines (2020). The higher the better? Defining the optimal beta-lactam target for critically ill patients to reach infection resolution and improve outcome. J. Intensive Care, 8 (1). LONDON: BMC. ISSN 2052-0492

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Abstract

ObjectivesBeta-lactam antibiotics are often subject to therapeutic drug monitoring, but breakpoints of target attainment are mostly based on expert opinions. Studies that show a correlation between target attainment and infection resolution are missing. This analysis investigated whether there is a difference in infection resolution based on two breakpoints of target attainment.MethodsAn outcome group out of 1392 critically ill patients treated with meropenem or piperacillin-tazobactam was formed due to different selection criteria. Afterwards, three groups were created: group 1=free drug concentration (f) was < 100% of the time (T) above the minimal inhibitory concentration (MIC) (< 100% fT >(MIC)), group 2=100% fT >(MIC)<(4xMIC), and group 3=100% fT >(4xMIC). Parameters for infection control, renal and liver function, and estimated and observed in-hospital mortality were compared between those groups. Statistical analysis was performed with one-way analysis of variance, Tukey post hoc test, U test, and bivariate logistic regression.ResultsThe outcome group consisted of 55 patients (groups 1-3, 17, 24, and 14 patients, respectively). Patients allocated to group 2 or 3 had a significantly faster reduction of the C-reactive protein in contrast to patients allocated to group 1 (p = 0.033 and p = 0.026). Patients allocated to group 3 had a worse renal function, a higher Acute Physiology and Chronic Health Evaluation (APACHE II) score, were older, and had a significantly higher in-hospital mortality compared to group 1 (p = 0.017) and group 2 (p = 0.001). The higher mortality was significantly influenced by worse liver function, higher APACHE II, and higher Sequential Organ Failure Assessment (SOFA) score and norepinephrine therapy.ConclusionAchieving the target 100% fT >(MIC) leads to faster infection resolution in the critically ill. However, there was no benefit for patients who reached the highest target of 100% fT >(4xMIC), although the mortality rate was higher possibly due to confounding effects. In conclusion, we recommend the target 100% fT >(MIC)<(4xMIC) for critically ill patients.Trial registrationNCT03985605

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Scharf, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Liebchen, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Paal, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Taubert, Max UNSPECIFIED UNSPECIFIED UNSPECIFIED Vogeser, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Irlbeck, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Zoller, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeder, Ines UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-310874
DOI:	10.1186/s40560-020-00504-w
Journal or Publication Title:	J. Intensive Care
Volume:	8
Number:	1
Date:	2020
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	2052-0492
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language AUGMENTED RENAL CLEARANCE; CARE-UNIT PATIENTS; PSEUDOMONAS-AERUGINOSA; ANTIBIOTIC LEVELS; SEPTIC PATIENTS; SEVERE SEPSIS; PIPERACILLIN; CEFTAZIDIME; THERAPY; MEROPENEM Multiple languages Critical Care Medicine Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31087