Epidemiology of Resistance Determinants Identified in Meropenem-Nonsusceptible Enterobacterales Collected as Part of a Global Surveillance Study, 2018 to 2019

Abstract

The objective of this study was to describe the frequency of resistance determinants in meropenem-nonsusceptible (MEM-NS) Enterobacterales isolates collected in 2018 and 2019 as a part of the ATLAS global surveillance program. Among a total of 39,368 Enterobacterales isolates collected in 2018 and 2019, 5.7% were MEM-NS (MIC ≥2 μg/mL). Among the different regions, the proportion of MEM-NS isolates ranged from 1.9% (North America) to 8.4% (Asia/Pacific). The majority of MEM-NS isolates collected were of the species Klebsiella pneumoniae (71.5%). Among the MEM-NS Enterobacterales isolates collected, metallo-β-lactamases (MBL) were identified in 36.7%, KPC in 25.5%, and OXA-48-like in 24.1%. The predominance of resistance mechanisms among MEM-NS isolates varied by region: MBLs were dominant in isolates collected in Africa and Middle East (AfME, 49%) and Asia/Pacific (59.4%), OXA-48-like carbapenemases were predominant in Europe (30%), and KPC in Latin America (51.9%) and North America (53.6%). NDM β-lactamases accounted for the majority of MBLs identified (88.4%). Of the 38 carbapenemase variants identified, NDM-1 (68.7%), KPC-2 (54.6%), OXA-48 (54.3%), and VIM-1 (76.1%) were the common variants within their respective families. Among the MEM-NS isolates, 7.9% co-carried two carbapenemases. Notably, the proportion of MEM-NS Enterobacterales increased from 4.9% in 2018 to 6.4% in 2019. The results of this study show a continuation of the trend of increasing carbapenem-resistance within clinical Enterobacterales with mechanisms of resistance varying across different regions. The existential threat to public health posed by the continued spread of nearly untreatable pathogens requires a multifaceted approach to prevent the collapse of modern medicine.

Keywords: Enterobacterales; carbapenem-nonsusceptible; carbapenemase.

FIG 1

Distribution of meropenem-nonsusceptible Enterobacterales collected globally and across different regions in 2018 and 2019. MEM-R, meropenem-resistant; MEM-I, meropenem-intermediate; n, total number of isolates collected. Countries contributing isolates from different regions included Israel, Jordan, Kuwait, Morocco, Nigeria, Qatar, Saudi Arabia, South Africa (Africa and Middle East); Australia, Hong Kong, India, Japan, South Korea, Malaysia, Philippines, Singapore, Taiwan, Thailand (Asia Pacific); Belgium, Croatia, Czech Republic, France, germane, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Netherlands, Poland, Portugal, Romania, Russia, Spain, Switzerland, Turkey, Ukraine, United Kingdom (Europe); Argentina, Brazil, Chile, Columbia, Costa Rica, Guatemala, Mexico, Panama, Venezuela (Latin America); Canada and United States (North America).

FIG 2

Distribution of all organisms and meropenem-nonsusceptible organisms among Enterobacterales isolates collected globally in 2018 and 2019. (A) Distribution of isolates of all organisms among Enterobacterales (N = 39,368). *Does not include isolates of E. cloacae; **Does not include isolates of K. aerogenes and K. pneumoniae; ***Includes Cronobacter spp. Escherichia vulneris, Hafnia alvei, Kosakonia cowanii, Lelliottia amnigena, Pantoea spp., Pluralibacter gergoviae, Raoultella spp., Serratia spp. Total number of isolates of each organism: Citrobacter spp. = 1,950; E. cloacae = 3,864; Enterobacter spp. = 1,179; E. coli = 11,728; K. aerogenes = 1,289; K. pneumoniae = 10,157; Klebsiella spp. = 2,375; M. morganii = 1,294; Proteus spp. = 2,403; Providencia spp. = 959; S. marcescens = 2,055; Others = 115. (B) Distribution of organisms among meropenem-nonsusceptible Enterobacterales (N = 2,228). *Does not include isolates of E. cloacae; **Does not include isolates of K. aerogenes and K. pneumoniae; Total number of isolates of each organism: Citrobacter spp. = 55; E. cloacae = 193; Enterobacter spp. = 24; E. coli = 148; K. aerogenes = 25; K. pneumoniae = 1,592; Klebsiella spp. = 38; M. morganii = 8; Proteus spp. = 18; Providencia spp. = 64; S. marcescens = 63.

FIG 3

Distribution of carbapenem resistance mechanisms identified in meropenem-nonsusceptible Enterobacterales isolates collected globally and across different regions in 2018 and 2019. (A) Meropenem-nonsusceptible isolates collected globally in 2018 and 2019 (N = 2,228). (B) Isolates collected in Africa and Middle East (N = 192). (C) Isolates collected in Asia Pacific (N = 505). (D) Isolates collected in Europe (N = 1020). (E) Isolates collected in Latin America (N = 401). (F) Isolates collected in North America (N = 110). AfME, Africa and Middle East; APAC, Asia Pacific; NDM, New Delhi metallo-β-lactamase; KPC, Klebsiella pneumoniae carbapenemase; OXA, oxacillinase; VIM, Verona integron-encoded metallo-β-lactamase; GES, Guiania extended-spectrum β-lactamase; VEB, Vietnamese extended-spectrum β-lactamase; MBL, Metallo-β-lactamase.

FIG 4

Proportion of carbapenem resistance mechanisms identified in meropenem-nonsusceptible Enterobacterales isolates collected globally and across different regions in 2018 and 2019. n, total number of isolates collected.

FIG 5

Frequency of meropenem nonsusceptibility among Enterobacterales isolates and associated carbapenemases, by region. AfME, Africa and Middle East; APAC, Asia/Pacific; Mem NS, Meropenem nonsusceptible, LATAM; Latin America. Countries contributing isolates from different regions included Israel, Jordan, Kuwait, Morocco, Nigeria, Qatar, Saudi Arabia, South Africa (Africa and Middle East); Australia, Hong Kong, India, Japan, South Korea, Malaysia, Philippines, Singapore, Taiwan, Thailand (Asia/Pacific); Belgium, Croatia, Czech Republic, France, germane, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Netherlands, Poland, Portugal, Romania, Russia, Spain, Switzerland, Turkey, Ukraine, United Kingdom (Europe); Argentina, Brazil, Chile, Columbia, Costa Rica, Guatemala, Mexico, Panama, Venezuela (Latin America); Canada and United States (North America).