Carbapenem-resistant Acinetobacter baumannii producing the carbapenemase OXA-23 in Tunisia
Keywords:
Acinetobacter baumannii, imipenem resistant, outbreak, OXA-23Abstract
Background: Aim: To analyze the mechanisms of resistance to carbapenems among imipenem resistant A. baumannii recovered from different wards at Charles Nicolle Hospital.
Methods: From January to December 2007, 50 carbapenem-resistant A. baumannii isolates were recovered from hospitalized patients. MICs were performed by agar dilution method and interpreted according to CLSI guidelines. Metallo-ß-lactamase production was evaluated using imipenem-EDTA disk synergy test. PCR and DNA sequencing targeting blaOXA genes were performed and pulsed field gel electrophoresis was used for epidemiologic study.
Results: Most of the isolates were obtained from patients hospitalized in surgery (62%) and Intensive Care Units (22%). All strains showed high level of resistance to ticarcillin (MIC50 > 2048μg/ml), ticarcillin-clavulanic acid (MIC50 >1024μg/ml), aztreonam (MIC50 = 512μg/ml), ceftazidim (MIC50 = 512μg/ml), imipenem (MIC50 = 512μg/ml), meropenem (MIC50 =128μg/ml) and cefepime (MIC50 = 256μg/ml). Metallo-ß-lactamase production was negative for all isolates. The co-existence of blaOXA-51-like/ blaOXA-23-like was detected in 82% (n= 41). The genes blaOXA- 24-like and blaOXA-58-like were not found in any isolate. All isolates harboured a blaOXA-51-like gene. Sequencing confirmed the presence of blaOXA-23 and blaOXA-69 genes. Eight distinct patterns were observed (A: 41 isolates, B: 1 isolate, C: 1 isolate, D: 1 isolate, E: 1 isolate, F: 2 isolates, G: 1 isolate, H: 2 isolates).
Conclusion: Production of OXA-23 was the important mechanism of resistance to carbapenem among A. baumannii. Strengthening of prevention measures are required to control further spread of carbapenemases in Tunisia.
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References
Dijkshoorn L, Nemec A, Seifert H. An Increasing Threat In Hospitals: Multidrug-Resistant Acinetobacter Baumannii. Nat Rev Microbiol 2007;5:939-51.
Livermore Dm. The Impact Of Carbapenemases On Antimicrobial Development And Therapy. Curr Opin Investig Drugs 2002;3:218-24.
Bonomo Ra, Szabo D. Mechanisms Of Multidrug Resistance In Acinetobacter Species And Pseudomonas Aeruginosa. Clin Infect Dis 2006;43:49-56.
Poirel L, Nordmann P. Carbapenem Resistance In Acinetobacter Baumannii: Mechanisms And Epidemiology. Clin Microbiol Infect 2006;12:826-36.
Walsh Tr, Toleman Ma, Poirel L, Nordmann P. Metallo-μ- Lactamases: The Quiet Before The Storm. Clin Microbiol Rev 2005;18:306-25.
Lee K, Yum Jh, Yong D, Et Al. Novel Acquired Metallo-μ- Lactamase Gene, Blasim-1, In A Class 1 Integron From Acinetobacter Baumannii Clinical Isolates From Korea. Antimicrob Agents Chemother 2005;49:4485-91.
Mendes Re, Bell Jm, Turnidge Jd, Castanheira M, Jones Rn. Emergence And Widespread Dissemination Of Oxa-23, -24/40 And -58 Carbapenemases Among Acinetobacter Spp. In Asia- Pacific Nations: Report From The Sentry Surveillance Program. J Antimicrob Chemother 2009;63:55-59.
Gupta V. Metallo-μ-Lactamases In Pseudomonas Aeruginosa And Acinetobacter Species. Expert Opin Investig Drugs 2008;17:131- 43.
Sekiguchi J, Morita K, Kitao T Et Al. Khm-1, A Novel Plasmid- Mediated Metallo-μ-Lactamase From A Citrobacter Freundii Clinical Isolate. Antimicrob Agents Chemother 2008;52:4194-97.
Lee K, Kim Mn, Choi Ty Et Al. Wide Dissemination Of Oxa-Type Carbapenemases In Clinical Acinetobacter Spp. Isolates From South Korea. Int J Antimicrob Agents 2009;33:520-24.
Poirel L, Rodriguez-Martinez Jm, Al Naiemi N, Debets- Ossenkopp Yj, Nordmann P. Characterization Of Dim-1, An Integron-Encoded Metallo-μ-Lactamase From A Pseudomonas Stutzeri Clinical Isolate In The Netherlands. Antimicrob Agents Chemother 2010;54:2420-24.
Feizabadi Mm, Fathollahzadeh B, Taherikalani M Et Al. Antimicrobial Susceptibility Patterns And Distribution Of Blaoxa Genes Among Acinetobacter Spp. Isolated From Patients At Tehran Hospitals. Jpn J Infect Dis 2008;61:274-78.
Zong Z, Lu X, Valenzuela Jk, Partridge Sr, Iredell J. An Outbreak Of Carbapenem-Resistant Acinetobacter Baumannii Producing Oxa-23 Carbapenemase In Western China. Int J Antimicrob Agents 2008;31:50-54.
Clinical And Laboratory Standards Institute. Performance Standards For Antimicrobial Susceptibility Testing. Sixteenth Information Supplement. M100-S16. Wayne, Pa: Clsi; 2006.
Jeon Bc, Jeong Sh, Bae Ik Et Al. Investigation Of A Nosocomial Outbreak Of Imipenem-Resistant Acinetobacter Baumannii Producing The Oxa-23 μ-Lactamase In Korea. J Clin Microbiol 2005;43:2241-2245.
Van Belkum A, Tassios Pt, Dijkshoorn L Et Al. Guidelines For The Validation And Application Of Typing Methods For Use In Bacterial Epidemiology. Clin Microbiol Infect 2007;13:1-46.
Da Silva Gj, Leitao Gj, Peixe L. Emergence Of Carbapenem- Hydrolyzing Enzymes In Acinetobacter Baumannii Clinical Isolates. J Clin Microbiol 1999;37:2109-110.
Zhou H, Yang Q, Yu Ys, Wei Zq, Li Lj. Clonal Spread Of Imipenem-Resistant Acinetobacter Baumannii Among Different Cities Of China. J Clin Microbiol 2007;45:4054-57.
Poirel L, Mansour W, Bouallegue O, Nordmann P. Carbapenem- Resistant Acinetobacter Baumannii Isolates From Tunisia Producing The Oxa-58-Like Carbapenem-Hydrolyzing Oxacillinase Oxa-97. Antimicrob Agents Chemother 2008;52:1613-17.
Paton R, Miles Rs, Hood J, Amyes Sg, Miles Rs, Amyes Sg. Ari 1: μ-Lactamase-Mediated Imipenem Resistance In Acinetobacter Baumannii. Int J Antimicrob Agents 1993;2:81-87.
Donald Hm, Scaife W, Amyes Sg, Young Hk. Sequence Analysis Of Ari-1, A Novel Oxa μ-Lactamase, Responsible For Imipenem Resistance In Acinetobacter Baumannii 6b92. Antimicrob Agents Chemother 2000;44:196-199.
Corvec S, Poirel L, Naas T, Drugeon H, Nordmann P. Genetics And Expression Of The Carbapenem-Hydrolyzing Oxacillinase Gene Blaoxa-23 In Acinetobacter Baumannii. Antimicrob Agents Chemother 2007;51:1530-33.
Marque S, Poirel L, Heritier C Et Al. Regional Occurrence Of Plasmid-Mediated Carbapenem-Hydrolyzing Oxacillinase Oxa- 58 In Acinetobacter Spp. In Europe. J Clin Microbiol 2005;43:4885-88.
Yu Ys, Yang Q, Xu Xw, Kong Hs, Xu Gy, Zhong By. Typing And Characterization Of Carbapenem-Resistant Acinetobacter Calcoaceticus-Baumannii Complex In A Chinese Hospital. J Med Microbiol 2004;53:653-56.
Dalla-Costa Lm, Coelho Jm, Souza Ha Et Al. Outbreak Of Carbapenem-Resistant Acinetobacter Baumannii Producing The Oxa-23 Enzyme In Curitiba, Brazil. J Clin Microbiol 2003;41:3403-406.
Qi C, Malczynski M, Parker M, Scheetz Mh. Characterization Of Genetic Diversity Of Carbapenem-Resistant Acinetobacter Baumannii Clinical Strains Collected From 2004 To 2007. J Clin Microbiol 2008;46:1106-109.
Lopez-Otsoa F, Gallego L, Towner Kj, Tysall L, Woodford N, Livermore Dm. Endemic Carbapenem Resistance Associated With Oxa-40 Carbapenemase Among Acinetobacter Baumannii Isolates From A Hospital In Northern Spain. J Clin Microbiol 2002;40:4741-43.
Da Silva Gj, Quinteira S, Bertolo E Et Al. Long-Term Dissemination Of An Oxa-40 Carbapenemase-Producing Acinetobacter Baumannii Clone In The Iberian Peninsula. J Antimicrob Chemother 2004;54:255-58.
Lolans K, Rice Tw, Munoz-Price Ls, Quinn Jp. Multicity Outbreak Of Carbapenem-Resistant Acinetobacter Baumannii Isolates Producing The Carbapenemase Oxa-40. Antimicrob Agents Chemother 2006;50:2941-45.
Bou G, Cervero G, Dominguez Ma, Quereda C, Martinez-Beltran J. Characterization Of A Nosocomial Outbreak Caused By A Multiresistant Acinetobacter Baumannii Strain With A Carbapenem-Hydrolyzing Enzyme: High-Level Carbapenem Resistance In A. Baumannii Is Not Due Solely To The Presence Of μ-Lactamases. J Clin Microbiol 2000;38:3299-305.
Poirel L, Marque S, Heritier C, Segonds C, Chabanon G, Nordmann P. Oxa-58, A Novel Class D μ-Lactamase Involved In Resistance To Carbapenems In Acinetobacter Baumannii. Antimicrob Agents Chemother 2005;49:202-208.
Carvalho Ap, Albano Rm, De Oliveira Dn, Cidade Da, Teixeira Lm, Marques Ede A. Characterization Of An Epidemic Carbapenem-Resistant Pseudomonas Aeruginosa Producing Spm- 1 Metallo-μ-Lactamase In A Hospital Located In Rio De Janeiro, Brazil. Microb Drug Resist 2006;12:103-108.
Limansky As, Mussi Ma, Viale Am. Loss Of A 29-Kilodalton Outer Membrane Protein In Acinetobacter Baumannii Is Associated With Imipenem Resistance. J Clin Microbiol 2002;40:4776-78.
Mussi Ma, Limansky As, Viale Am. Acquisition Of Resistance To Carbapenems In Multidrug-Resistant Clinical Strains Of Acinetobacter Baumannii: Natural Insertional Inactivation Of A Gene Encoding A Member Of A Novel Family Of μ-Barrel Outer Membrane Proteins. Antimicrob Agents Chemother 2005;49:1432-40.
Naas T, Levy M, Hirschauer C, Marchandin H, Nordmann P. Outbreak Of Carbapenem-Resistant Acinetobacter Baumannii Producing The Carbapenemase Oxa-23 In A Tertiary Care Hospital Of Papeete, French Polynesia. J Clin Microbiol 2005;43:4826-29.
