Global Dissemination of Carbapenemase-Producing Klebsiella pneumoniae: Epidemiology, Genetic Context, Treatment Options, and Detection Methods

Chang-Ro Lee, Jung Hun Lee, Kwang Seung Park, Young Bae Kim, Byeong Chul Jeong, Sang Hee Lee, Chang-Ro Lee, Jung Hun Lee, Kwang Seung Park, Young Bae Kim, Byeong Chul Jeong, Sang Hee Lee

Abstract

The emergence of carbapenem-resistant Gram-negative pathogens poses a serious threat to public health worldwide. In particular, the increasing prevalence of carbapenem-resistant Klebsiella pneumoniae is a major source of concern. K. pneumoniae carbapenemases (KPCs) and carbapenemases of the oxacillinase-48 (OXA-48) type have been reported worldwide. New Delhi metallo-β-lactamase (NDM) carbapenemases were originally identified in Sweden in 2008 and have spread worldwide rapidly. In this review, we summarize the epidemiology of K. pneumoniae producing three carbapenemases (KPCs, NDMs, and OXA-48-like). Although the prevalence of each resistant strain varies geographically, K. pneumoniae producing KPCs, NDMs, and OXA-48-like carbapenemases have become rapidly disseminated. In addition, we used recently published molecular and genetic studies to analyze the mechanisms by which these three carbapenemases, and major K. pneumoniae clones, such as ST258 and ST11, have become globally prevalent. Because carbapenemase-producing K. pneumoniae are often resistant to most β-lactam antibiotics and many other non-β-lactam molecules, the therapeutic options available to treat infection with these strains are limited to colistin, polymyxin B, fosfomycin, tigecycline, and selected aminoglycosides. Although, combination therapy has been recommended for the treatment of severe carbapenemase-producing K. pneumoniae infections, the clinical evidence for this strategy is currently limited, and more accurate randomized controlled trials will be required to establish the most effective treatment regimen. Moreover, because rapid and accurate identification of the carbapenemase type found in K. pneumoniae may be difficult to achieve through phenotypic antibiotic susceptibility tests, novel molecular detection techniques are currently being developed.

Keywords: KPC; Klebsiella pneumoniae; NDM; OXA-48-like; carbapenemase; epidemiology.

Figures

FIGURE 1
FIGURE 1
Epidemiological features of KPC-producing Klebsiella pneumoniae. (1) USA; (2) Colombia; (3) Brazil; (4) Argentina; (5) Italy; (6) Greece; (7) Poland; (8) Israel; (9) China; (10) Taiwan; (11) Canada; (12) Spain; (13) France; (14) Belgium; (15) Netherlands; (16) Germany; (17) UK; (18) Ireland; (19) Sweden; (20) Finland; (21) Hungary; (22) India; (23) South Korea; (24) Australia; (25) Mexico; (26) Cuba; (27) Puerto Rico; (28) Uruguay; (29) Portugal; (30) Switzerland; (31) Austria; (32) Czech Republic; (33) Denmark; (34) Norway; (35) Croatia; (36) Turkey; (37) Algeria; (38) Egypt; (39) South Africa; (40) Iran; (41) United Arab Emirates; (42) Pakistan; (43) Russia; (44) Japan.
FIGURE 2
FIGURE 2
Structural features of representative genetic environments of blaKPC-2, blaNDM-1, and blaOXA-48 genes.(A) The blaKPC-2-containing Tn4401 transposon from the plasmid pNYC (GenBank accession no. EU176011) is shown in horizontal arrows. Two inverted repeat sequences (IRL and IRR) of Tn4401 are depicted in triangles at either end. Tn4401 has five isoforms which differ by deletions (68–255 bp) just upstream of the blaKPC gene [(a) deletion of 99 bp; (b) no deletion; (c) deletion of 215 bp; (d) deletion of 68 bp; (e) deletion of 255 bp]. (B) The blaNDM-1 genetic context of pNDM_MGR194 (GenBank accession no. KF220657) is shown in horizontal arrows. (C) The blaOXA-48-containing Tn1999 transposon from the plasmid pOXA-48 (GenBank accession no. JN626286) is shown in horizontal arrows.
FIGURE 3
FIGURE 3
Epidemiological features of NDM-producing K. pneumoniae. (1) India; (2) Pakistan; (3) Bangladesh; (4) Canada; (5) USA; (6) Colombia; (7) Spain; (8) France; (9) UK; (10) Italy; (11) Switzerland; (12) Greece; (13) Turkey; (14) Saudi Arabia; (15) Oman; (16) United Arab Emirates; (17) Kuwait; (18) Morocco; (19) South Africa; (20) China; (21) South Korea; (22) Japan; (23) Taiwan; (24) Singapore; (25) Australia; (26) Mexico; (27) Guatemala; (28) Brazil; (29) Ireland; (30) Germany; (31) Netherlands; (32) Czech Republic; (33) Poland; (34) Hungary; (35) Romania; (36) Croatia; (37) Norway; (38) Sweden; (39) Finland; (40) Russia; (41) Algeria; (42) Tunisia; (43) Libya; (44) Egypt; (45) Kenya; (46) Madagascar; (47) Mauritius; (48) Israel; (49) Iraq; (50) Iran; (51) Yemen; (52) Sri Lanka; (53) Nepal; (54) Thailand; (55) Vietnam; (56) Malaysia, (57) New Zealand.
FIGURE 4
FIGURE 4
Epidemiological features of OXA-48-like-producing K. pneumoniae. (1) Turkey; (2) Morocco; (3) Tunisia; (4) Libya; (5) Egypt; (6) India; (7) Argentina; (8) Spain; (9) France; (10) Germany; (11) Switzerland; (12) Belgium; (13) Netherlands; (14) UK; (15) Italy; (16) Israel; (17) Saudi Arabia; (18) Kuwait; (19) Lebanon; (20) Japan; (21) Canada; (22) USA; (23) Ireland; (24) Poland; (25) Finland; (26) Hungary; (27) Romania; (28) Bulgaria; (29) Greece; (30) Russia; (31) Algeria; (32) Senegal; (33) South Africa; (34) United Arab Emirates; (35) Oman; (36) Iran; (37) Sri Lanka; (38) Thailand; (39) Singapore; (40) South Korea; (41) Taiwan; (42) Australia; (43) New Zealand.

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