title: Rapid determination of quinolone resistance in Acinetobacter spp.
abstract: In the treatment of serious bacterial infections, the rapid institution of appropriate antimicrobial chemotherapy may be lifesaving. Choosing the correct antibiotic or combination of antibiotics is becoming very important, as multidrug resistance is found in many pathogens. Using a collection of 75 well-characterized multidrug-resistant (MDR) Acinetobacter sp. isolates, we show that PCR followed by electrospray ionization mass spectrometry (PCR/ESI-MS) and base composition analysis of PCR amplification products can quickly and accurately identify quinolone resistance mediated by mutations in the quinolone resistance-determining regions of gyrA and parC, two essential housekeeping genes. Single point mutations detected by PCR/ESI-MS in parC (found in 55/75 of the isolates) and in gyrA (found in 66/75 of the isolates) correlated with susceptibility testing and sequencing. By targeting resistance determinants that are encoded by genes with highly conserved DNA sequences (e.g., gyrA and parC), we demonstrate that PCR/ESI-MS can provide critical information for resistance determinant identification and can inform therapeutic decision making in the treatment of Acinetobacter sp. infections.
authors.affiliation: Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Hujer
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Hujer
authors.forename: Andrea
authors.initials: A
authors.lastname: Endimiani
authors.forename: Jodi M
authors.initials: JM
authors.lastname: Thomson
authors.forename: Mark D
authors.initials: MD
authors.lastname: Adams
authors.forename: Karrie
authors.initials: K
authors.lastname: Goglin
authors.forename: Philip N
authors.initials: PN
authors.lastname: Rather
authors.forename: Thuy-Trang D
authors.initials: TT
authors.lastname: Pennella
authors.forename: Christian
authors.initials: C
authors.lastname: Massire
authors.forename: Mark W
authors.initials: MW
authors.lastname: Eshoo
authors.forename: Rangarajan
authors.initials: R
authors.lastname: Sampath
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Blyn
authors.forename: David J
authors.initials: DJ
authors.lastname: Ecker
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
mesh_terms: D000150:Acinetobacter / Q000187:drug effects*; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics*; D024881:Drug Resistance, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D015363:Quinolones / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D015363:Quinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase