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J Infect Dis. Emergence of Colistin-Resistance in Extremely Drug-Resistant Acinetobacter baumannii Containing a Novel pmrCAB Operon During Colistin Therapy of Wound Infections
[Source: The Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]
Emergence of Colistin-Resistance in Extremely Drug-Resistant Acinetobacter baumannii Containing a Novel pmrCAB Operon During Colistin Therapy of Wound Infections
E. Lesho 1,a, E. J. Yoon 5, P. McGann 1, E. Snesrud 1, Y. Kwak 1, M. Milillo 1, F. Onmus-Leone 1, L. Preston 1, K. St. Clair 3, M. Nikolich 2, H. Viscount 4, G. Wortmann 3, M. Zapor 3, C. Grillot-Courvalin 5, P. Courvalin 5, R. Clifford 1 and P. E. Waterman 1
Author Affiliations: <SUP>1</SUP>Multidrug-Resistant Organism Repository and Surveillance Network <SUP>2</SUP>Department of Emerging Bacterial Infections, Walter Reed Army Institute of Research, Silver Spring <SUP>3</SUP>Infectious Diseases Service <SUP>4</SUP>Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Maryland <SUP>5</SUP>Unit? des Agents Antibact?riens, Institut Pasteur, Paris, France
Correspondence: Emil Lesho, 503 Robert Grant Ave, Silver Spring, MD 20910 (emil.lesho@us.army.mil).
Presented in part: American Society of Microbiology General Meeting June 16th?19th, 2012, San Francisco, California; Poster 653; Wellcome Trust 2012 Infectious Disease Genomics & Global Health Scientific Conference October 1st?3rd 2012, Cambridge, United Kingdom: Poster# P4.
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.
Key words
Colistin-resistant Acinetobacter baumannii - infection control - translational research
Received December 14, 2012. Accepted March 13, 2013.
Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2013. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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Emergence of Colistin-Resistance in Extremely Drug-Resistant Acinetobacter baumannii Containing a Novel pmrCAB Operon During Colistin Therapy of Wound Infections
E. Lesho 1,a, E. J. Yoon 5, P. McGann 1, E. Snesrud 1, Y. Kwak 1, M. Milillo 1, F. Onmus-Leone 1, L. Preston 1, K. St. Clair 3, M. Nikolich 2, H. Viscount 4, G. Wortmann 3, M. Zapor 3, C. Grillot-Courvalin 5, P. Courvalin 5, R. Clifford 1 and P. E. Waterman 1
Author Affiliations: <SUP>1</SUP>Multidrug-Resistant Organism Repository and Surveillance Network <SUP>2</SUP>Department of Emerging Bacterial Infections, Walter Reed Army Institute of Research, Silver Spring <SUP>3</SUP>Infectious Diseases Service <SUP>4</SUP>Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Maryland <SUP>5</SUP>Unit? des Agents Antibact?riens, Institut Pasteur, Paris, France
Correspondence: Emil Lesho, 503 Robert Grant Ave, Silver Spring, MD 20910 (emil.lesho@us.army.mil).
Presented in part: American Society of Microbiology General Meeting June 16th?19th, 2012, San Francisco, California; Poster 653; Wellcome Trust 2012 Infectious Disease Genomics & Global Health Scientific Conference October 1st?3rd 2012, Cambridge, United Kingdom: Poster# P4.
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.
Key words
Colistin-resistant Acinetobacter baumannii - infection control - translational research
Received December 14, 2012. Accepted March 13, 2013.
Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2013. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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