title: Correlation of β-Lactamase Production and Colistin Resistance among Enterobacteriaceae Isolates from a Global Surveillance Program.
abstract: The increasing use of carbapenems for treating multidrug-resistant (MDR) Gram-negative bacterial infections has contributed to the global dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Serine and metallo-β-lactamases (MBLs) that hydrolyze carbapenems have become prevalent and endemic in some countries, necessitating the use of older classes of agents, such as colistin. A total of 19,719 isolates of Enterobacteriaceae (excluding Proteeae and Serratia spp., which have innate resistance to colistin) were collected from infected patients during 2012 and 2013 in a global surveillance program and tested for antimicrobial susceptibility using CLSI methods. Isolates of CRE were characterized for carbapenemases and extended-spectrum β-lactamases (ESBLs) by PCR and sequencing. Using EUCAST breakpoints, the rate of colistin susceptibility was 98.4% overall, but it was reduced to 88.0% among 482 carbapenemase-positive isolates. Colistin susceptibility was higher among MBL-positive isolates (92.6%) than those positive for a KPC (87.9%) or OXA-48 (84.2%). Of the agents tested, only tigecycline (MIC90, 2 to 4 μg/ml) and aztreonam-avibactam (MIC90, 0.5 to 1 μg/ml) consistently tested with low MIC values against colistin-resistant, ESBL-positive, and carbapenemase-positive isolates. Among the 309 (1.6%) colistin-resistant isolates from 10 species collected in 38 countries, 58 carried a carbapenemase that included KPCs (38 isolates), MBLs (6 isolates), and OXA-48 (12 isolates). These isolates were distributed globally (16 countries), and 95% were Klebsiella pneumoniae. Thirty-nine (67.2%) isolates carried additional ESBL variants of CTX-M, SHV, and VEB. This sample of Enterobacteriaceae demonstrated a low prevalence of colistin resistance overall. However, the wide geographic dispersion of colistin resistance within diverse genus and species groups and the higher incidence observed among carbapenemase-producing MDR pathogens are concerning.
authors.affiliation: AstraZeneca Pharmaceuticals, Waltham, Massachusetts, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Bradford
authors.affiliation: International Health Management Associates, Inc., Schaumburg, Illinois, USA kkazmierczak@ihmainc.com.
authors.forename: Krystyna M
authors.initials: KM
authors.lastname: Kazmierczak
authors.affiliation: International Health Management Associates, Inc., Schaumburg, Illinois, USA.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Biedenbach
authors.affiliation: International Health Management Associates, Inc., Schaumburg, Illinois, USA.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Wise
authors.affiliation: International Health Management Associates, Inc., Schaumburg, Illinois, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Hackel
authors.affiliation: International Health Management Associates, Inc., Schaumburg, Illinois, USA.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Sahm
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism; D003091:Colistin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D004756:Enterobacteriaceae Infections / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001618:beta-Lactamases; C063912:carbapenemase; D003091:Colistin