Universität zu Köln

Dimitriou, Vassiliki, Biehl, Lena M., Hamprecht, Axel ORCID: 0000-0003-1449-5780, Vogel, Wichard, Doerfel, Daniela, Peter, Silke, Schafhausen, Philippe, Rohde, Holger, von Lilienfeld-Toal, Marie, Klassert, Tilman E., Slickers, Peter, Ehricht, Ralf, Slevogt, Hortense, Christ, Hildegard ORCID: 0000-0003-3235-2994, Hellmich, Martin, Farowski, Fedja, Tsakmaklis, Anastasia, Higgins, Paul G. ORCID: 0000-0001-8677-9454, Seifert, Harald and Vehreschild, Maria J. G. T. (2019). Controlling intestinal colonization of high-risk haematology patients with ESBL-producing Enterobacteriaceae: a randomized, placebo-controlled, multicentre, Phase II trial (CLEAR). J. Antimicrob. Chemother., 74 (7). S. 2065 - 2075. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2091

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Abstract

Objectives We assessed the efficacy and safety of an oral antimicrobial regimen for short- and long-term intestinal eradication of ESBL-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EC/KP) in immunocompromised patients. Methods We performed a randomized (2:1), double-blind multicentre Phase II study in four haematology-oncology departments. Patients colonized with ESBL-EC/KP received a 7day antimicrobial regimen of oral colistin (2x10(6)IU 4x/day), gentamicin (80mg 4x/day) and fosfomycin (three administrations of 3g every 72h), or placebo. Faecal, throat and urine specimens were collected on day 0, 62, 112, 28 +/- 4 and 42 +/- 4 after treatment initiation, and the quantitative burden of ESBL-EC/KP, resistance genes and changes in intestinal microbiota were analysed. Clinicaltrials.gov: NCT01931592. Results As the manufacture of colistin powder was suspended worldwide, the study was terminated prematurely. Overall, 29 (18 verum/11 placebo) out of 47 patients were enrolled. The short-term intestinal eradication was marginal at day 6 (verum group 15/18, 83.3% versus placebo 2/11, 18.2%; relative risk 4.58, 95% CI 1.29-16.33; Fisher's exact test P=0.001) and not evident at later timepoints. Quantitative analysis showed a significant decrease of intestinal ESBL-EC/KP burden on day 6. Sustained intestinal eradication (day 28+42) was not achieved (verum, 38.9% versus placebo, 27.3%; P=0.299). In the verum group, mcr-1 genes were detected in two faecal samples collected after treatment. Microbiome analysis showed a significant decrease in alpha diversity and a shift in beta diversity. Conclusions In this prematurely terminated study of a 7day oral antimicrobial eradication regimen, short-term ESBL-EC/KP suppression was marginal, while an altered intestinal microbiota composition was clearly apparent.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dimitriou, Vassiliki UNSPECIFIED UNSPECIFIED UNSPECIFIED Biehl, Lena M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hamprecht, Axel UNSPECIFIED orcid.org/0000-0003-1449-5780 UNSPECIFIED Vogel, Wichard UNSPECIFIED UNSPECIFIED UNSPECIFIED Doerfel, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Peter, Silke UNSPECIFIED UNSPECIFIED UNSPECIFIED Schafhausen, Philippe UNSPECIFIED UNSPECIFIED UNSPECIFIED Rohde, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED von Lilienfeld-Toal, Marie UNSPECIFIED UNSPECIFIED UNSPECIFIED Klassert, Tilman E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Slickers, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Ehricht, Ralf UNSPECIFIED UNSPECIFIED UNSPECIFIED Slevogt, Hortense UNSPECIFIED UNSPECIFIED UNSPECIFIED Christ, Hildegard UNSPECIFIED orcid.org/0000-0003-3235-2994 UNSPECIFIED Hellmich, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Farowski, Fedja UNSPECIFIED UNSPECIFIED UNSPECIFIED Tsakmaklis, Anastasia UNSPECIFIED UNSPECIFIED UNSPECIFIED Higgins, Paul G. UNSPECIFIED orcid.org/0000-0001-8677-9454 UNSPECIFIED Seifert, Harald UNSPECIFIED UNSPECIFIED UNSPECIFIED Vehreschild, Maria J. G. T. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-136386
DOI:	10.1093/jac/dkz124
Journal or Publication Title:	J. Antimicrob. Chemother.
Volume:	74
Number:	7
Page Range:	S. 2065 - 2075
Date:	2019
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2091
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FECAL MICROBIOTA TRANSPLANTATION; CEPHALOSPORIN-RESISTANT ENTEROBACTERIACEAE; LACTAMASE-PRODUCING ENTEROBACTERIACEAE; SELECTIVE DIGESTIVE DECONTAMINATION; SPECTRUM BETA-LACTAMASES; KLEBSIELLA-PNEUMONIAE; ESCHERICHIA-COLI; DOUBLE-BLIND; DECOLONIZATION; CARRIAGE Multiple languages Infectious Diseases; Microbiology; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13638