Multiyear, Multinational Survey of the Incidence and Global Distribution of Metallo-β-Lactamase-Producing Enterobacteriaceae and Pseudomonas aeruginosa

Abstract

T he worldwide dissemination of Gram-negative bacteria producing extended-spectrum ␤-lactamases (ESBLs) in the late 20th century resulted in a dearth of treatment options and an increase in the therapeutic use of carbapenems (1, 2). In turn, reports of carbapenem-resistant and carbapenemase-producing bacteria became more frequent (3-5). One important group of carbapenemases of special concern is the metallo-␤-lactamases (MBLs). These enzymes belong to Ambler class B and require 1 or 2 zinc ions for enzyme activity (6). Many MBLs are chromosomally encoded in environmental bacteria or species that can act as opportunistic pathogens. However, a number of MBLs, including the NDM-type, IMP-type, and VIM-type MBLs, are plasmid encoded and readily transferable among clinically significant bacterial species, including Klebsiella pneumoniae and Escherichia coli (3). Notably, MBLs are often coproduced with Ambler class A and C serine ␤-lactamases, including ESBLs and AmpC enzymes (7).MBLs hydrolyze all ␤-lactams except monobactams, including aztreonam, and are not inhibited by any of the commercially available ␤-lactamase inhibitors. Although aztreonam is active against many Gram-negative bacteria, it is inactive against isolates that produce ESBLs, KPC carbapenemases, or plasmid-encoded or stably derepressed, chromosomally encoded AmpC ␤-lactamases, thereby limiting its potential utility against MBL-producing isolates that also contain one or more of these serine ␤-lactamases (8). Avibactam is a non-␤-lactam ␤-lactamase inhibitor that is active against Ambler class A and C and some class D (OXA-48) enzymes (9, 10). Aztreonam combined with avibactam has demonstrated activity against Enterobacteriaceae that coproduce MBLs and class A or class C ␤-lactamases (11, 12).As part of a global surveillance program, the molecular basis of carbapenem resistance in Gram-negative pathogens was investigated in order to determine the incidence of acquired MBLs and the geographic regions in which these ␤-lactamases are most problematic. This report describes the isolation and regional distribution of MBL-positive Enterobacteriaceae and Pseudomonas aeruginosa isolates collected from 2012 to 2014. MATERIALS AND METHODSNonduplicate bacterial isolates from intra-abdominal, urinary tract, skin and soft tissue, lower respiratory tract, and bloodstream infections were collected from 202 sites in 40 countries located in five major geographic regions (Asia-Pacific, Europe, Latin America, the Middle East-Africa, and North America). A predefined number of isolates of selected bacterial species were collected from each site regardless of antibiotic susceptibility. Organism collection, transport, confirmation of organism identification, susceptibility testing, molecular characterization, quality assurance of

Coexistence of mcr-1 and bla NDM-1 in Escherichia coli from Venezuela

“…The coexistence of mcr-1 with a carbapenemase is especially worrisome, as therapeutic options in such cases are very limited. Currently, the carbapenemase New Delhi metallo-␤-lactamase 1 (NDM-1) is broadly disseminated worldwide (8), although it has been scarcely described in South America (9,10). In this work, we have detected mcr-1-positive isolates from different origins in Venezuela, as well as the coexistence of this resistance gene with bla NDM-1 .…”

In Vitro Activity of Aztreonam-Avibactam against Enterobacteriaceae and Pseudomonas aeruginosa Isolated by Clinical Laboratories in 40 Countries from 2012 to 2015

“…Avibactam protects ␤-lactams from hydrolysis by class A enzymes (including TEM, CTX-M ESBLs, and KPCs), class C enzymes (e.g., CMY, ACT, FOX), and some class D enzymes (e.g., OXA-48, OXA-139) (2,(10)(11)(12)(13). When combined with avibactam, aztreonam is able to inhibit cell wall synthesis in MBL-producing bacteria, despite the presence of cocarried serine ␤-lactamases (2,9,14).…”

Coproduction of KPC-18 and VIM-1 Carbapenemases by Enterobacter cloacae: Implications for Newer β-Lactam–β-Lactamase Inhibitor Combinations

“…However, E. cloacae G6809 was resistant to aztreonam due to the additional production of KPC-18 and the chromosomal AmpC, which together masked this unique susceptibility phenotype that is helpful in identifying MBL-producing organisms. As expected, addition of avibactam restored the susceptibility of E. cloacae G6809 to aztreonam with an MIC of 0.5/4 g/ml, as this combination inhibits MBL, KPC, and AmpC (24).…”