Thursday, June 8, 2023
| Carbapenemases (no. isolates) | Geographic location (no. isolates) | Sequence types (no. isolates) |
|---|---|---|
| KPCs (50) | ||
| KPC-2 (35) | Argentina (4), Brazil (5), Colombia (8), Greece (1), Guatemala (4), Israel (2), Puerto Rico (2), United States (4), Venezuela (1), Vietnam (4) | ST10 (3), ST46 (2), ST69 (2), ST95 (3), ST131 (7), ST349 (1), ST405 (3), ST410 (3), ST538 (1), ST540 (1), ST607 (1), ST617 (1), ST648 (1), ST1193 (1), ST1196 (1), ST2172 (1), ST2279 (1), ST3580 (1) |
| KPC-3 (14) | Colombia (1), Israel (1), Italy (8), United States (4) | ST12 (1), ST73 (1), ST131 (7), ST141 (1), ST191 (1), ST617 (1), ST973 (1), ST1148 (1) |
| KPC-18 (1) | United States (1) | ST131 (1) |
| NDMs (66) | ||
| NDM-1 (19) | Egypt (3), Guatemala (2), Kuwait (1), Morocco (4), Philippines (1), Romania (1), Russia (3), Serbia (1), Thailand (2), Vietnam (1) | ST38 (1), ST44 (1), ST69 (1), ST95 (1), ST131 (4), ST167 (3), ST345 (1), ST361 (1), ST617 (2), ST1193 (1), ST1434 (1), ST1470 (1), ST4553 (1), |
| NDM-4 (1) | Vietnam (1) | ST405 (1) |
| NDM-5 (40) | Canada (1), Egypt (16), Italy (2), Jordan (4), Lebanon (1), Thailand (8), United Kingdom (2), Vietnam (6) | ST131 (1), ST156 (1), ST167 (11), ST361 (4), ST405 (3), ST410 (12), ST448 (2), ST648 (4), ST2003 (2) |
| NDM-6 (1) | Guatemala (1) | ST38 (1) |
| NDM-7 (5) | Philippines (4), Vietnam (1) | ST156 (2), ST410 (1), ST448 (1), ST5229 (1) |
| OXA-48–like (96) | ||
| OXA-48 (40) | Austria (1), Belgium (2), Egypt (3), Georgia (3), Israel (1), Lebanon (2), Mexico (1), Morocco (2), Saudi Arabia (1), Spain (2), Thailand (1), Tunisia (1), Turkey (15), United Kingdom (1), Vietnam (4) | ST10 (2), ST12 (1), ST34 (1), ST38 (8), ST58 (1), ST131 (2), ST224 (1), ST349 (1), ST354 (6), ST361 (1), ST405 (4), ST410 (2), ST624 (1), ST648 (1), ST1431 (1), ST11260 (6) |
| OXA-181 (48) | Egypt (6), Germany (1), Jordan (15), Kuwait (1), Lebanon (1), Malaysia (1), South Africa (2), Taiwan (1), Thailand (2), Turkey (18) | ST46 (1), ST131 (1), ST167 (2), ST205 (1), ST354 (1), ST410 (21), ST648 (1), ST1284 (18), ST1487 (1), ST6802 (1) |
| OXA-232 (5) | Malaysia (1), Mexico (3), Thailand (1) | ST127 (1), ST131 (1), ST361 (3) |
| OXA-244 (3) | Egypt (3) | ST58 (1), ST648 (1), ST1722 (1) |
| VIMs (4) | ||
| VIM-1 (2) | Greece (1), Spain (1) | ST88 (1), ST404 (1) |
| VIM-23 (2) | Mexico (2) | ST410 (2) |
| IMPs (2) | ||
| IMP-59 (2) | Australia (2) | ST357 (2) |
| Two carbapenemases (11) | ||
| NDM-1 + VIM-1 (1) | Egypt (1) | ST131 (1) |
| NDM-1 + OXA-181 (2) | Egypt (2) | ST46 (2) |
| NDM-5 + OXA-48 (1) | Egypt (1) | ST167 (1) |
| NDM-5 + OXA-181 (5) | Egypt (3), South Korea (1), Vietnam (1) | ST410 (4), ST448 (1) |
| NDM-5 + OXA-232 (2) | United Kingdom (2) | ST2083 (2) |
Table. Global molecular epidemiology of 229 carbapenemase-producing Escherichia coli isolates, 36 countries, 2015–2017*
*KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-β-lactamase; OXA, oxacillinase; ST, sequence type ; VIM, Verona integron‒encoded metallo-β-lactamase.
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The goal of this activity is to describe the geographic distribution of different carbapenemase genes (including associations with dominant sequence types, clades, and underlying mobile genetic elements), other β-lactamases, antibiotic resistance genes, and virulence factors, based on short read whole genome sequencing of 229 carbapenemase-producing Escherichia coli (2015-17) from 36 countries (including 20 lower- and middle-income countries).
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Overall, 218 isolates were positive for a single carbapenemase and 11 isolates were positive for 2 carbapenemases (Table). The OXA-48–like (n = 106) were the most common carbapenemases, followed by NDMs (n = 77), KPCs (n = 50), VIMs (n = 5), and IMPs (n = 2). The OXA-48–like carbapenemases consisted of OXA-48 (n = 41), OXA-181 (n = 55), OXA-244 (n = 3), and OXA-232 (n = 7). E. coli with OXA-48, OXA-181, and OXA-232 had a global distribution. OXA-244 was limited to Egypt (Table). The NDMs consisted of NDM-1 (n = 22), NDM-4 (n = 1), NDM-5 (n = 48), NDM-6 (n = 1), and NDM-7 (n = 5). E. coli with NDM-1 and NDM-5 had a global distribution. NDM-4 was limited to Vietnam and NDM-6 to Guatemala; NDM-7 was found in the Philippines and Vietnam (Table). The KPCs consisted of KPC-2 (n = 35), KPC-3 (n = 14), and KPC-18 (n = 1). E. coli with KPC-2 and KPC-3 had a global distribution, and KPC-18 was obtained from the United States (Table). E. coli with VIMs (VIM-1 and VIM-23) were found in Greece, Spain, Mexico, and Egypt; E. coli with IMP-59 were obtained from Australia (Table).
We identified 2 major STs (ST410 [20%] and ST131 [12%]) and 3 minor STs (ST1284 [8%], ST167 [7%], and ST405 [5%]) among this collection. The next most common STs did not fulfill the definition of a dominant ST: ST38 (n = 10 [4%]), ST354 (n = 7 [3%]), ST361 (n = 9 [4%]), ST648 (n = 8 [4%]), and ST11260 (n = 6 [3%]).
ST410 was the most common ST (n = 45/229 [20%]) and was positive for KPC-2 (7%), NDM-5 (27%), NDM-7 (2%), OXA-48 (4%), OXA-181 (47%), and VIM-23 [4%]) (Appendix Table 1). ST410 belonged to 2 subclades: B3/H24Rx (n = 10) and B4/H24RxC (n = 35)[21].
ST131 was the second most common ST (n = 26/229 [12%]) and was positive for KPC-2 (n = 8), KPC-3 (n = 7), KPC-18 (n = 1), NDM-1 (n = 5), NDM-5 (n = 1), OXA-48 (n = 2), OXA-181 (n = 1), and OXA-232 (n = 1). One NDM-1 isolate was also positive for VIM-1. ST131 belonged to clade A/H41 (n = 2) and subclades C1_nonM27 (n = 10), C1_M27 (n = 4), and C2 (n = 10). We also note the global distribution of different minor STs (ST1284, ST167, ST405) and their clades (Appendix).
We determined quinolone resistance–determining regions mutations, β-lactamases (noncarbapenemases), aminoglycoside modifying enzymes, and plasmid replicon types among the different E. coli STs (Appendix Table 1). TEM-1, CTX-M-15, aac(6')-Ib-cr, and sul1 were common among isolates.
We assessed the presence of 37 putative virulence factors among the different dominant STs (Appendix Table 2). The following factors were present among most of isolates: fimH (100%), fyuA (55%), traT (64%), and iss (52%). Some virulence factors were associated with certain STs: papA (81%), iha (77%), sat (81%), fyuA (100%) usp (100%), ompT (100%), and malX (100%) with ST131, and astA (100%) and iutA (100%) with ST1284. ST131 had the highest overall number of virulence genes (n = 11), and ST410 had the lowest number of virulence genes (n = 2) (Appendix Table 2).
Because of the limitations of short-read sequencing[30], analyses of the immediate carbapenemase gene flanking regions and plasmids harboring carbapenemase genes were insufficient, especially for bla OXA-48 and bla VIMs. We obtained results for 20/22 of bla NDM-1, 2/2 of bla NDM-4, 46/48 of bla NDM-5, 1/1 of bla NDM-6, 4/5 of bla NDM-7, 34/35 of bla KPC-2, 14/14 of bla KPC-3, 1/1 of bla KPC-18, 1/41 bla OXA-48, 55/55 of bla OXA-181, 3/3 of bla OXA-244, and 7/7 of bla OXA-232.
Among blaKPC-2, 15 were situated in Tn4401 elements (Tn4401a [n = 4] in ST131 and ST46, Tn4401b [n = 9] in 7 STs, and Tn4401e [n = 2] in ST131 and ST1193). Nineteen were associated with non-Tn4401 mobile elements (NTMKPC)[31], including 4 ST131 and 3 ST405 strains. The bla KPC-3 genes were associated with Tn4401a (n = 9), Tn4401b (n = 3), and Tn4401d (n = 2). The bla KPC-18 was located on a novel Tn4401 variant (186 bp deletion). The bla NDMs were located on truncated Tn125 elements, and the bla NDM upstream regions showed substantial diversities with various IS element insertions (e.g., IS630, ISAba125, IS1, and IS903 with bla NDM-1; ISEcp1 and IS1 with bla NDM-5; and IS5 with bla NDM-7).
All blaOXA-232 genes were located on the same 6.1 kb colKp3 plasmids (pOXA-232)[32]. Sequence similarities (95%–100%) of blaKPC-3 isolates with previously sequenced plasmids in GenBank showed that most (n = 9) were harbored within IncFIBQil plasmids[33]; 2 KPC-3 genes were within pKPC-CAV1193[34], 1 blaKPC-3 was within the IncFIA plasmid pBK30683[35], and 1 blaKPC-3 was in the IncI2 plasmid pBK15692[36]. The blaOXA-181 (n = 55) were situated within Tn2013 harbored on the identical IncX3 plasmids with 99%–100% similarities to plasmid p72_X3_OXA181[37]. p72_X3_ OXA181 contained the IncX3 and truncated ColKp3 replicons[13].
