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A trial with IgY chicken antibodies to eradicate faecal carriage of Klebsiella pneumoniae and Escherichia coli producing extended-spectrum beta-lactamases.

Posted by on in 2015
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  • Jonsson AK1Larsson A2Tängdén T1Melhus Å2Lannergård A3. 2015. Infect Ecol Epidemiol. 5:28224. doi: 10.3402/iee.v5.28224. eCollection 2015.
  • 1Section of Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • 2Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
  • 3Section of Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; anders.lannergard@akademiska.se.

Abstract

BACKGROUND:

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is an emerging therapeutic challenge, especially in the treatment of urinary tract infections. Following an outbreak of CTX-M-15 Klebsiella pneumoniae in Uppsala, Sweden, an orphan drug trial on IgYchicken antibodies was undertaken in an attempt to eradicate faecal carriage of ESBL-producing K. pneumoniae and Escherichia coli.

METHODS:

Hens were immunised with epitopes from freeze-dried, whole-cell bacteria (ESBL-producing K. pneumoniae and E. coli) and recombinant proteins of two K. pneumoniae fimbriae subunits (fimH and mrkD). The egg yolks were processed according to good manufacturing practice and the product was stored at-20°C until used. Using an internal database from the outbreak and the regular laboratory database, faecal carriers were identified and recruited from May 2005 to December 2013. The participants were randomised in a placebo-controlled 1:1 manner.

RESULTS:

From 749 eligible patients, 327 (44%) had deceased, and only 91 (12%) were recruited and signed the informed consent. In the initial screening performed using the polymerase chain reaction, 24 participants were ESBL positive and subsequently randomised and treated with either the study drug or a placebo. The study was powered for 124 participants. Because of a very high dropout rate, the study was prematurely terminated. From the outbreak cohort (n=247), only eight patients were screened, and only one was positive with the outbreak strain in faeces.

CONCLUSIONS:

The present study design, using IgY chicken antibodies for the eradication of ESBL-producing K. pneumonia and E. coli, was ineffective in reaching its goal due to high mortality and other factors resulting in a low inclusion rate. Spontaneous eradication of ESBL-producing bacteria was frequently observed in recruited participants, which is consistent with previous reports.

KEYWORDS:

CTX-M-15; Enterobacteriaceae; Escherichia coli; IgY chicken antibody; Klebsiella pneumoniae; avian antibody; clonal outbreak; extended spectrum beta-lactamase; faecal carriage; immunotherapy; infectious control; stool colonisation

PMID:
 
26560861
 
[PubMed] 
Free PMC Article
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