Emergence of Colistin-Resistance in Extremely Drug-Resistant Acinetobacter baumannii Containing a Novel pmrCAB Operon During Colistin Therapy of Wound Infections

• Published in: The Journal of infectious diseases Vol. 208; no. 7; pp. 1142 - 1151
• Main Authors: Lesho, Emil, Yoon, Eun-Jeong, McGann, Patrick, Snesrud, Erik, Kwak, Yoon, Milillo, Michael, Onmus-Leone, Fatma, Preston, Lan, St. Clair, Kristina, Nikolich, Mikeljon, Viscount, Helen, Wortmann, Glenn, Zapor, Michael, Grillot-Courvalin, Catherine, Courvalin, Patrice, Clifford, Robert, Waterman, Paige E.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.10.2013
• Subjects: Acinetobacter; Acinetobacter baumannii; Acinetobacter baumannii - drug effects; Acinetobacter baumannii - genetics; Acinetobacter baumannii - isolation & purification; Acinetobacter Infections - drug therapy; Acinetobacter Infections - microbiology; Adult; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotics; BACTERIA; Bacterial Proteins - genetics; Bacteriology; Biological and medical sciences; Colistin - pharmacology; Colistin - therapeutic use; Drug Resistance, Bacterial; Fundamental and applied biological sciences. Psychology; Genes; Genetic mutation; Genomes; Genotype; Humans; Infections; Infectious diseases; Longitudinal Studies; Medical sciences; Microbial Sensitivity Tests; Microbiology; Miscellaneous; Molecular Typing; Operon; Operons; Phylogenetics; Point Mutation; Surveillance; Transcription Factors - genetics; Wound Infection - drug therapy; Colistin; Cyclic peptides; Operon; Neisseriaceae; Wound; Infection; Resistance; Acinetobacter baumannii; Antibiotic; Treatment; Polypeptide; Bacteria; Micrococcales; Antibacterial agent; Extreme environment; Colistin-resistant Acinetobacter baumannii; infection control; translational research
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jit293

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 oipmrC1A1B, 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.