title: Multiyear, Multinational Survey of the Incidence and Global Distribution of Metallo-β-Lactamase-Producing Enterobacteriaceae and Pseudomonas aeruginosa.
abstract: Metallo-β-lactamases (MBLs) hydrolyze all classes of β-lactams except monobactams and are not inhibited by classic serine β-lactamase inhibitors. Gram-negative pathogens isolated from patient infections were collected from 202 medical centers in 40 countries as part of a global surveillance study from 2012 to 2014. Carbapenem-nonsusceptible Enterobacteriaceae and Pseudomonas aeruginosa were characterized for bla genes encoding VIM, IMP, NDM, SPM, and GIM variants using PCR and sequencing. A total of 471 MBL-positive isolates included the following species (numbers of isolates are in parentheses): P. aeruginosa (308), Klebsiella spp. (85), Enterobacter spp. (39), Proteeae (16), Citrobacter freundii (12), Escherichia coli (6), and Serratia marcescens (5) and were submitted by sites from 34 countries. Of these, 69.6% were collected in 9 countries (numbers of isolates are in parentheses): Russia (72), Greece (61), Philippines (54), Venezuela (29), and Kuwait, Nigeria, Romania, South Africa, and Thailand (20 to 25 isolates each). Thirty-two different MBL variants were detected (14 VIM, 14 IMP, and 4 NDM enzymes). Seven novel MBL variants were encountered in the study, each differing from a previously reported variant by one amino acid substitution: VIM-42 (VIM-1 [V223I]), VIM-43 (VIM-4 [A24V]), VIM-44 (VIM-2 [K257N]), VIM-45 (VIM-2 [T35I]), IMP-48 (IMP-14 [I69T]), IMP-49 (IMP-18 [V49F]), and NDM-16 (NDM-1 [R264H]). The in vitro activities of all tested antibiotics against MBL-positive Enterobacteriaceae were significantly reduced with the exception of that of aztreonam-avibactam (MIC90, 0.5 to 1 μg/ml), whereas colistin was the most effective agent against MBL-positive P. aeruginosa isolates (>97% susceptible). Although the global percentage of isolates encoding MBLs remains relatively low, their detection in 12 species, 34 countries, and all regions participating in this surveillance study is concerning.
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: Sharon
authors.initials: S
authors.lastname: Rabine
authors.affiliation: International Health Management Associates, Inc., Schaumburg, Illinois, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Hackel
authors.affiliation: AstraZeneca Pharmaceuticals LP, Waltham, Massachusetts, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: McLaughlin
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: Samuel K
authors.initials: SK
authors.lastname: Bouchillon
authors.affiliation: International Health Management Associates, Inc., Schaumburg, Illinois, USA.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Sahm
authors.affiliation: AstraZeneca Pharmaceuticals LP, Waltham, Massachusetts, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Bradford
mesh_terms: D001398:Aztreonam / Q000494:pharmacology; D004755:Enterobacteriaceae / Q000201:enzymology* / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000453:epidemiology* / Q000382:microbiology; D006115:Greece / Q000453:epidemiology; D006801:Humans; D007730:Kuwait / Q000453:epidemiology; D008826:Microbial Sensitivity Tests; D009549:Nigeria / Q000453:epidemiology; D010679:Philippines / Q000453:epidemiology; D011552:Pseudomonas Infections / Q000453:epidemiology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000302:isolation & purification; D012426:Russia / Q000453:epidemiology; D013019:South Africa / Q000453:epidemiology; D011795:Surveys and Questionnaires; D013785:Thailand / Q000453:epidemiology; D014687:Venezuela / Q000453:epidemiology; D018440:beta-Lactam Resistance / Q000502:physiology; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D001618:beta-Lactamases; D001398:Aztreonam