Emergence and Spread of OXA-48-Like Carbapenemase-Producing Enterobacteriaceae

Song Wonkeun; Hoon Jeong Seok; Lee Jacob; Soon Lee Seung; Lee Kyungwon

doi:10.14192/kjnic.2015.20.1.7

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Wonkeun, Seok, Jacob, Seung, and Kyungwon: Emergence and Spread of OXA-48-Like Carbapenemase-Producing Enterobacteriaceae

Original Article

J Nosocomial Infect Control 2013;20(1):7-18.

Published online: 3 May 2013

DOI: https://doi.org/10.14192/kjnic.2015.20.1.7

Emergence and Spread of OXA-48-Like Carbapenemase-Producing Enterobacteriaceae

Song Wonkeun, Hoon Jeong Seok, Lee Jacob, Soon Lee Seung, Lee Kyungwon

¹Department of Laboratory Medicine, Hallym University College of Medicine, Seoul, Korea

²Department of Laboratory Medicine and Research Institute for Antimicrobial Resistance, Yonsei University College of Medicine, Seoul, Korea

³Department of Internal Medicine, Hallym University College of Medicine, Seoul, Korea

Address reprint requests to Wonkeun Song, Department of Laboratory Medicine, Hallym University College of Medicine, 1, Singil-ro, Yeongdeungpo-gu, Seoul 150-950, Korea Tel: 02-829-5250, Fax: 02-847-2403 E-mail: swonkeun@hallym.or.kr

Received 13 March 2015 Accepted 16 June 2015

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Since 2001, ten more OXA-48 variants have been identified. Shewanella spp. has been thought to be the original host for OXA-48-like enzymes. These enzymes strongly hydrolyze penicillins and weakly hydrolyze carbapenems, with very weak activity against broad-spectrum cephalosporins. The OXA-48-like genes are always plasmid-borne and have been located in insertion sequences. OXA-48-like carbapenemases have been identified mainly from Turkey, North African countries, the Middle East, and India. Furthermore, the emergence and outbreak of OXA-48-like producers in Korea have been reported recently. Because some OXA-48-like-producing Enterobacteriaceae isolates do not exhibit resistance to broad-spectrum cephalosporins and only decreased susceptibility to carbapenems, their detection can be difficult. Adequate screening and detection methods are required to prevent and control the dissemination of OXA-48-like-producing Enterobacteriaceae.

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Keywords: Class D carbapenemase, Enterobacteriaceae, OXA-48-like

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Table 1.

Characteristics of first reported OXA-48-like carbapenemases

OXA-48-like	Location	Organism	Country	Year	Identified other β-lactamases	ST	MIC (µg/mL)		Reference
OXA-48-like	Location	Organism	Country	Year	Identified other β-lactamases	ST	CTX	CAZ	Reference	FEP	ATM	ETP	IPM	MEM
OXA-48	Pl	KPN	Turkey	2001	TEM-1, OXA-47, SHV-2a		64	512	32	512		64	64	[3]
OXA-48b	Ch	SXI	China											[86]
OXA-162	Pl	KPN	Turkey	2009	TEM-1, SHV-1, OXA-14			32	4		8	4	1	[6]
OXA-163	Pl	KPN	Argentina	2008	TEM-1		32	256	32	16	0.38	0.5	0.25	[17]
	Pl	ECL	Argentina	2008	TEM-1		â256	â256	â256	â256	2	0.5	0.5	[17]
OXA-181	Pl	KPN	Oman*	2010	TEM-1, OXA-1, SHV-11, CTX-M-15	11	128	32	16	128	2	0.5	0.5	[10]
OXA-199	Ch	SXI	China											[86]
OXA-204	Pl	KPN	Tunisia*		SHV-1, OXA-1, CMY-4, CTX-M-14	383	128	64	16	32	2	0.5	0.5	[14]
OXA-232	Pl	KPN	France*	2011	TEM-1, SHV-1, OXA-1, CTX-M-15, NDM-1	14	â256	â256	â256	â256	â32	â32	â32	[15]
	Pl	KPN	France*	2011	TEM-1, SHV-1, OXA-1, CTX-M-15	14	â256	â256	â256	â256	â32	3	12	[15]
	Pl	ECO	France*	2011	OXA-1, CTX-M-15	2968	3	8	16	16	0.38	0.25	0.12	[15]
OXA-244	Pl	KPN	Spain	2011	CTX-M-15	392								[87]
OXA-245	Pl	KPN	Spain	2011	CTX-M-15	437	â64	â64			â32	â32	â32	[87]
OXA-247	Pl	KPN	Argentina	2010	TEM-1, SHV-1	37	1	16	8	32	â256	16	16	[88]

*Had been travelled or hospitalized in India.

Abbreviations: ST, sequence type; MIC, minimal inhibitory concentration; CTX, cefotaxime; CAZ, ceftazidime; FEP, cefepime; ATM, aztreonam; ETP, ertapenem; IPM, imipenem; MEM, meropenem; Pl, plasmid; Ch, chromosome; KPN, Klebsiella pneumoniae; SXI, Shewanella xiamenensis; ECL, Enterobacter cloacae; ECO, Escherichia coli.

Table 2.

Activities of carbapenemases

Activity	Carbapenemase
Activity	Class A	Class B	Class D
Active site	Serine	Zn⁺⁺	Serine
Aztreonam hydrolysis	Yes	No	No
Boronic acid inhibition	Yes	No	No
EDTA inhibition	No	Yes	No

Fig. 1.

Modified Hodge test (A) and carbapenemase inhibition test (B) results for the KPC-2-producing K. pneumoniae (1), OXA-232-producing K. pneumoniae (2), DHA-1-producing K. pneumoniae (3), and NDM-1-producing K. pneumoniae isolate (4) are shown. (1) The positive MHT, negative EDTA and positive PBA, suggesting KPC (class A) production. (2) The positive MHT, negative EDTA and negative PBA, suggesting OXA (class D) production. (3) The negative MHT, negative EDTA and positive PBA, suggesting AmpC (class C) production. (4) The weak-positive MHT, positive EDTA and negative PBA, suggesting metallo-β-lactamase (class B) production. Abbreviations: ETP, ertapenem; MEM, meropenem; PBA, phenylboronic acid.

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