Dissemination of imipenem-resistant Acinetobacter baumannii with new plasmid-borne blaOXA-72 in Taiwan

BMC Infectious Diseases

Chang-Phone Fung²  Po-Ren Hsueh⁴  Po-Liang Lu³  Te-Li Chen²  Chi-Ling Chang²  Chien-Pei Chen²  Han-Chuan Chuang⁶  Yi-Tzu Lee⁵  Su-Pen Yang¹  Shu-Chen Kuo² 

[1] Institute of Emergency and Critical Care Medicine, National Yang-Ming University, No.155, Sec. 2, Linong Street., Beitou District, Taipei 112, Taiwan;Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei 112, Taiwan;Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, No. 100, Zihyou 1st Rd., Kaohsiung City 807, Taiwan;Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, No. 1, Changde St., Zhongzheng District, Taipei City 100, Taiwan;Emergency Department, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei 112, Taiwan;Division of Infectious Disease, Department of Medicine, Buddhist Taipei Tzu Chi General Hospital, No. 289, Jianguo Rd., Xindian Dist., New Taipei City 231, Taiwan

关键词: Bla_OXA-72;    Carbapenemase;    Acinetobacter baumannii;    Imipenem-resistant;   

Others  :  1147057
DOI  :  10.1186/1471-2334-13-319

 received in 2013-04-17, accepted in 2013-07-10,  发布年份 2013

【 摘 要 】

Background

The systemic surveillance of imipenem-resistant Acinetobacter baumannii (IRAB) from multicenters in Taiwan revealed the emergence of isolates with bla_OXA-72. This study described their genetic makeup, mechanism of spread, and contribution to carbapenem resistance.

Methods

Two hundred and ninety-one non-repetitive isolates of A. baumannii were collected from 10 teaching hospitals from different geographical regions in Taiwan from June 2007 to September 2007. Minimal inhibitory concentrations (MICs) were determined by agar dilution. Clonality was determined by pulsed-field gel electrophoresis. Plasmid was extracted and digested by restriction enzymes, and subsequently analyzed by electrophoresis and Southern blot for bla_OXA-72. The flanking regions of bla_OXA-72 were determined by inverse PCR. The contribution of bla_OXA-72 to imipenem MIC was determined by transforming plasmids carrying bla_OXA-72 into imipenem-susceptible A. baumannii.

Results

Among 142 IRAB in Taiwan, 27 harbored bla_OXA-72; 22 originated from Southern Taiwan, 5 from Central Taiwan, and none from Northern Taiwan. There were two major clones. The bla_OXA-72 was identified in the plasmids of all isolates. Two genetic structures flanking plasmid-borne bla_OXA-72 were identified and shared identical sequences in certain regions; the one described in previous literature was present in only one isolate, and the new one was present in the remaining isolates. Introduction of bla_OXA-72 resulted in an increase of imipenem MIC in the transformants. The overexpression of bla_OXA-72 mRNA in response to imipenem further supported the contribution of bla_OXA-72.

Conclusions

In conclusion, isolates with new plasmid-borne bla_OXA-72 were found to be disseminated successfully in Southern Taiwan. The spread of the resistance gene depended on clonal spread and dissemination of a new plasmid. Bla_OXA-72 in these isolates directly led to their imipenem-resistance.

【 授权许可】

   
2013 Kuo et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Neonakis IK, Spandidos DA, Petinaki E: Confronting multidrug-resistant Acinetobacter baumannii: a review. Int J Antimicrob Agents 2011, 37:102-109.
• [2]McCracken M, DeCorby M, Fuller J, Loo V, Hoban DJ, Zhanel GG, Mulvey MR: Identification of multidrug- and carbapenem-resistant Acinetobacter baumannii in Canada: results from CANWARD 2007. J Antimicrob Chemother 2009, 64:552-555.
• [3]Kwon KT, Oh WS, Song JH, Chang HH, Jung SI, Kim SW, Ryu SY, Heo ST, Jung DS, Rhee JY, Shin SY, Ko KS, Peck KR, Lee NY: Impact of imipenem resistance on mortality in patients with Acinetobacter bacteraemia. J Antimicrob Chemother 2007, 59:525-530.
• [4]Karageorgopoulos DE, Falagas ME: Current control and treatment of multidrug-resistant Acinetobacter baumannii infections. Lancet Infect Dis 2008, 8:751-762.
• [5]Poirel L, Nordmann P: Carbapenem resistance in Acinetobacter baumannii: mechanisms and epidemiology. Clin Microbiol Infect 2006, 12:826-836.
• [6]Lee YT, Kuo SC, Chiang MC, Yang SP, Chen CP, Chen TL, Fung CP: Emergence of carbapenem-resistant non-baumannii species of Acinetobacter harboring a blaOXA-51-like gene that is intrinsic to A. baumannii. Antimicrob Agents Chemother 2012, 56:1124-1127.
• [7]Poirel L, Naas T, Nordmann P: Diversity, epidemiology, and genetics of class D beta-lactamases. Antimicrob Agents Chemother 2010, 54:24-38.
• [8]Peleg AY, Seifert H, Paterson DL: Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev 2008, 21:538-582.
• [9]Werneck JS, Picao RC, Carvalhaes CG, Cardoso JP, Gales AC: OXA-72-producing Acinetobacter baumannii in Brazil: a case report. J Antimicrob Chemother 2011, 66:452-454.
• [10]Barnaud G, Zihoune N, Ricard JD, Hippeaux MC, Eveillard M, Dreyfuss D, Branger C: Two sequential outbreaks caused by multidrug-resistant Acinetobacter baumannii isolates producing OXA-58 or OXA-72 oxacillinase in an intensive care unit in France. J Hosp Infect 2010, 76:358-360.
• [11]Lee K, Kim MN, Choi TY, Cho SE, Lee S, Whang DH, Yong D, Chong Y, Woodford N, Livermore DM: Wide dissemination of OXA-type carbapenemases in clinical Acinetobacter spp. isolates from South Korea. Int J Antimicrob Agents 2009, 33:520-524.
• [12]Di Popolo A, Giannouli M, Triassi M, Brisse S, Zarrilli R: Molecular epidemiological investigation of multidrug-resistant Acinetobacter baumannii strains in four Mediterranean countries with a multilocus sequence typing scheme. Clin Microbiol Infect 2011, 17:197-201.
• [13]Lu PL, Doumith M, Livermore DM, Chen TP, Woodford N: Diversity of carbapenem resistance mechanisms in Acinetobacter baumannii from a Taiwan hospital: spread of plasmid-borne OXA-72 carbapenemase. J Antimicrob Chemother 2009, 63:641-647.
• [14]Chen TL, Siu LK, Wu RC, Shaio MF, Huang LY, Fung CP, Lee CM, Cho WL: Comparison of one-tube multiplex PCR, automated ribotyping and intergenic spacer (ITS) sequencing for rapid identification of Acinetobacter baumannii. Clin Microbiol Infect 2007, 13:801-806.
• [15]Clinical and Laboratory Standards Institute: Performance Standards for Antimicrobial Susceptibility testing; Twenty-First Information Supplement. Wayne, PA: CLSI; 2011. [CLSI document M100-S21]
• [16]Turton JF, Ward ME, Woodford N, Kaufmann ME, Pike R, Livermore DM, Pitt TL: The role of ISAba1 in expression of OXA carbapenemase genes in Acinetobacter baumannii. FEMS Microbiol Lett 2006, 258:72-77.
• [17]Ellington MJ, Kistler J, Livermore DM, Woodford N: Multiplex PCR for rapid detection of genes encoding acquired metallo-beta-lactamases. J Antimicrob Chemother 2007, 59:321-322.
• [18]Huang LY, Chen TL, Lu PL, Tsai CA, Cho WL, Chang FY, Fung CP, Siu LK: Dissemination of multidrug-resistant, class 1 integron-carrying Acinetobacter baumannii isolates in Taiwan. Clin Microbiol Infect 2008, 14:1010-1019.
• [19]Chen TL, Wu RCC, Shaio MF, Fung CP, Cho WL: Acquisition of a plasmid-borne blaOXA-58 gene with an upstream IS1008 insertion conferring a high level of carbapenem resistance to Acinetobacter baumannii. Antimicrob Agents Chemother 2008, 52:2573-2580.
• [20]Kuo SC, Fung CP, Lee YT, Chen CP, Chen TL: Bacteremia due to Acinetobacter genomic species 10. J Clin Microbiol 2010, 48:586-590.
• [21]Chen TL, Chang WC, Kuo SC, Lee YT, Chen CP, Siu LK, Cho WL, Fung CP: Contribution of a plasmid-borne blaOXA-58 gene with its hybrid promoter provided by IS1006 and an ISAba3-like element to beta-lactam resistance in Acinetobacter genomic species 13TU. Antimicrob Agents Chemother 2010, 54:3107-3112.
• [22]Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT, Monnet DL: Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012, 18:268-281.
• [23]Tian GB, Adams-Haduch JM, Bogdanovich T, Pasculle AW, Quinn JP, Wang HN, Doi Y: Identification of diverse OXA-40 group carbapenemases, including a novel variant, OXA-160, from Acinetobacter baumannii in Pennsylvania. Antimicrob Agents Chemother 2011, 55:429-432.
• [24]Lee MH, Chen TL, Lee YT, Huang L, Kuo SC, Yu KW, Hsueh PR, Dou HY, Su IJ, Fung CP: Dissemination of multidrug-resistant Acinetobacter baumannii carrying blaOXA-23 from hospitals in central Taiwan. J Microbiol Immunol Infect 2012. Sep 22 [Epub ahead of print]
• [25]D'Andrea MM, Giani T, D'Arezzo S, Capone A, Petrosillo N, Visca P, Luzzaro F, Rossolini GM: Characterization of pABVA01, a plasmid encoding the OXA-24 carbapenemase from Italian isolates of Acinetobacter baumannii. Antimicrob Agents Chemother 2009, 53:3528-3533.
• [26]Merino M, Acosta J, Poza M, Sanz F, Beceiro A, Chaves F, Bou G: OXA-24 carbapenemase gene flanked by XerC/XerD-like recombination sites in different plasmids from different Acinetobacter species isolated during a nosocomial outbreak. Antimicrob Agents Chemother 2010, 54:2724-2727.