Emergence of colistin-resistance in extremely drug-resistant acinetobacter baumannii containing a novel pmrCAB operon during colistin therapy of wound infections

Emil Lesho*, Eun Jeong Yoon, Patrick Mcgann, Erik Snesrud, Yoon Kwak, Michael Milillo, Fatma Onmus-Leone, Lan Preston, Kristina St. Clair, Mikeljon Nikolich, Helen Viscount, Glenn Wortmann, Michael Zapor, Catherine Grillot-Courvalin, Patrice Courvalin, Robert Clifford, Paige E. Waterman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

Abstract

Background. Colistin resistance is of concern since it is increasingly needed to treat infections caused by bacteria resistant to all other antibiotics and has been associated with poorer outcomes. Longitudinal data from in vivo series are sparse.Methods. Under a quality-improvement directive to intensify infection-control measures, extremely drug-resistant (XDR) bacteria undergo phenotypic and molecular analysis.Results. Twenty-eight XDR Acinetobacter baumannii isolates were longitudinally recovered during colistin therapy. Fourteen were susceptible to colistin, and 14 were resistant to colistin. Acquisition of colistin resistance did not alter resistance to other antibiotics. Isolates had low minimum inhibitory concentrations of an investigational aminoglycoside, belonged to multi-locus sequence type 94, were indistinguishable by pulsed-field gel electrophoresis and optical mapping, and harbored a novel pmrC1A1B allele. Colistin resistance was associated with point mutations in the pmrA1 and/or pmrB genes. Additional pmrC homologs, designated eptA-1 and eptA-2, were at distant locations from the operon. Compared with colistin-susceptible isolates, colistin-resistant isolates displayed significantly enhanced expression of pmrC1A1B, eptA-1, and eptA-2; lower growth rates; and lowered fitness. Phylogenetic analysis suggested that colistin resistance emerged from a single progenitor colistin-susceptible isolate.Conclusions. We provide insights into the in vivo evolution of colistin resistance in a series of XDR A. baumannii isolates recovered during therapy of infections and emphasize the importance of antibiotic stewardship and surveillance.

Original languageEnglish
Pages (from-to)1142-1151
Number of pages10
JournalJournal of Infectious Diseases
Volume208
Issue number7
DOIs
StatePublished - 1 Oct 2013
Externally publishedYes

Keywords

  • Colistin-resistant Acinetobacter baumannii
  • infection control
  • translational research

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