Epidemiology of Carbapenem Resistance Determinants Identified in Meropenem-Nonsusceptible Enterobacterales Collected as Part of a Global Surveillance Program, 2012 to 2017

Abstract

To estimate the incidence of carbapenem-resistant Enterobacterales (CRE), a global collection of 81,781 surveillance isolates of Enterobacterales collected from patients in 39 countries in five geographic regions from 2012 to 2017 was studied. Overall, 3.3% of isolates were meropenem-nonsusceptible (MIC ≥2 μg/ml), ranging from 1.4% (North America) to 5.3% (Latin America) of isolates by region. Klebsiella pneumoniae accounted for the largest number of meropenem-nonsusceptible isolates (76.7%). The majority of meropenem-nonsusceptible Enterobacterales carried KPC-type carbapenemases (47.4%), metallo-β-lactamases (MBLs; 20.6%) or OXA-48-like β-lactamases (19.0%). Forty-three carbapenemase sequence variants (8 KPC-type, 4 GES-type, 7 OXA-48-like, 5 NDM-type, 7 IMP-type, and 12 VIM-type) were detected, with KPC-2, KPC-3, OXA-48, NDM-1, IMP-4, and VIM-1 identified as the most common variants of each carbapenemase type. The resistance mechanisms responsible for meropenem-nonsusceptibility varied by region. A total of 67.3% of all carbapenemase-positive isolates identified carried at least one additional plasmid-mediated or intrinsic chromosomally encoded extended-spectrum β-lactamase, AmpC β-lactamase, or carbapenemase. The overall percentage of meropenem-nonsusceptible Enterobacterales increased from 2.7% in 2012 to 2014 to 3.8% in 2015 to 2017. This increase could be attributed to the increasing proportion of carbapenemase-positive isolates that was observed, most notably among isolates carrying NDM-type MBLs in Asia/South Pacific, Europe, and Latin America; OXA-48-like carbapenemases in Europe, Middle East/Africa, and Asia/South Pacific; VIM-type MBLs in Europe; and KPC-type carbapenemases in Latin America. Ongoing CRE surveillance combined with a global antimicrobial stewardship strategy, sensitive clinical laboratory detection methods, and adherence to infection control practices will be needed to interrupt the spread of CRE.

Keywords: Enterobacterales; carbapenem resistant; carbapenem-resistant Enterobacterales; surveillance.

FIG 1

Distribution of meropenem-nonsusceptible Enterobacterales collected from 2012 to 2017. MEM-I, meropenem-intermediate, MIC of 2 μg/ml; MEM-R, meropenem-resistant, MIC of ≥4 μg/ml. Global, all surveyed regions; LA, Latin America (Argentina, Brazil, Chile, Colombia, Mexico, and Venezuela); EUR, Europe (Austria, Belgium, the Czech Republic, Denmark, France, Germany, Greece, Hungary, Italy, the Netherlands, Poland, Portugal, Romania, Russia, Spain, Sweden, Turkey, and the United Kingdom); AP, Asia/South Pacific (Australia, China, Hong Kong, Japan, Malaysia, the Philippines, South Korea, Taiwan, and Thailand); MEA, Middle East/Africa (Israel, Kenya, Kuwait, Nigeria, and South Africa); NA, North America (the United States). Isolates obtained from patients in North America were collected from 2012 to 2016 only.

FIG 2

Distribution of carbapenem resistance mechanisms identified in meropenem-nonsusceptible Enterobacterales isolates. (A) Meropenem-nonsusceptible isolates collected in all surveyed regions (n = 2,666). (B) Isolates collected in Europe (n = 1,441). (C) Isolates collected in Latin America (n = 689). (D) Isolates collected in Asia/South Pacific (n = 294). (E) Isolates collected in the Middle East/Africa (n = 140). (F) Isolates collected in North America (n = 102,2012 to 2016 only). No Cpase detected, no gene encoding a carbapenemase was detected by PCR. MBL + OXA-48-like (n = 52) included NDM + OXA-48-like (Europe, n = 26; Asia/South Pacific, n = 17; Middle East/Africa, n = 1) and VIM + OXA-48-like (Europe, n = 6; Middle East/Africa, n = 2). MBL + KPC (n = 11) included VIM + KPC (Europe, n = 7), NDM + KPC (Latin America, n = 1; Asia/South Pacific, n = 1) and IMP + KPC (Asia/South Pacific, n = 2). MBL + GES was composed of NDM + GES carbapenemase (Latin America, n = 2). Two MBLs were composed of VIM + NDM (Europe, n = 1).

FIG 3

Comparison of the distribution of carbapenem resistance mechanisms identified in meropenem-nonsusceptible Enterobacterales isolates collected from 2012 to 2014 and from 2015 to 2017. Region (no. of isolates collected in 2012 to 2014/no. of isolates collected in 2015 to 2017): Global, all surveyed regions (38,190/43,591); LA, Latin America (5,317/7,729); EUR, Europe (18,301/21,850); AP, Asia/South Pacific (7,087/7,051); MEA, Middle East/Africa (3,281/3,690); NA, North America (4,204/3,271 [2015 to 2016 only]). No Cpase detected, no gene encoding a carbapenemase was detected by PCR. Isolates carrying multiple carbapenemases were counted for each individual carbapenemase type.