Affiliation:
1. International Health Management Associates, Inc., Schaumburg, Illinois, USA
2. AstraZeneca Pharmaceuticals LP, Waltham, Massachusetts, USA
Abstract
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 (MIC
90
, 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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology