Expression analysis of drug-resistant gene (blaOXA-51) in carbapenemases producing Acinetobacter baumannii treated with imipenem/sulbactam combination
DOI:
https://doi.org/10.1590/s2175-97902020000419048Keywords:
Acinetobacter baumannii. blaOXA-51. Carbapenemases. Imipenem. Sulbactam.Abstract
Drug-resistant Acinetobacter baumannii is a frightening reality. The aim of this study is to examine the expression profiles of blaOXA-51 gene in carbapenemases producing A. baumannii treated with imipenem/sulbactam combination. Carbapenemases producing A. baumannii was identified among clinical isolates of A. baumannii obtained from patients at Shahid Rajaee hospital, Gachsaran, Iran, from January to June 2018. Synergism testing of imipenem/sulbactam on carbapenemases producing A. baumannii was carried out by broth microdilution method. Eventually, the expression of blaOXA-51 gene was carried out to investigate the inhibitory properties of imipenem/sulbactam combination against carbapenemases producing A. baumannii using quantitative real time RT-PCR. Among A. baumannii isolates, 24% were carbapenemases producing A. baumannii. Imipenem/ sulbactam combination revealed synergistic and partial synergistic effect for all tested isolates (FIC= 0.313-0.75). Finally, imipenem/sulbactam combination displayed significant down-regulation of blaOXA-51 gene in carbapenemases producing A. baumannii. Imipenem synergizes with sulbactam against carbapenemases producing A. baumannii by targeting of the blaOXA-51 gene.
Downloads
References
Antunes NT, Lamoureaux TL, Toth M, Stewart NK, Frase H, Vakulenko SB. Class D ß-lactamases: are they all carbapenemases? Antimicrob Agents Chemother. 2014;58(4):2119-25.
Bahador A, Raoofian R, Pourakbari B, Taheri M, Hashemizadeh Z, Hashemi FB. Genotypic and antimicrobial susceptibility of carbapenem-resistant Acinetobacter baumannii: analysis of is Aba elements and bla OXA-23-like genes including a new variant. Front Microbiol. 2015;6:1249.
Biglari S, Hanafiah A, Mohd Puzi S, Ramli R, Rahman M, Lopes BS. Antimicrobial resistance mechanisms and genetic diversity of multidrug-resistant Acinetobacter baumannii isolated from a teaching hospital in Malaysia. Microb Drug Resist. 2017;23(5):545-55.
Brown S, Young HK, Amyes SG. Characterisation of OXA-51, a novel class D carbapenemase found in genetically unrelated clinical strains of Acinetobacter baumannii from Argentina. Clin Microbio Infect. 2005;11(1):15-23.
Bush K. Proliferation and significance of clinically relevant ß-lactamases. Ann N Y Acad Sci. 2013;1277:84-90.
Chen LK, Kuo SC, Chang KC, Cheng CC, Yu PY, Chang CH, Chen TY, Tseng CC. Clinical antibiotic-resistant Acinetobacter baumannii strains with higher susceptibility to environmental phages than antibiotic-sensitive strains. Sci Rep. 2017;7(1):6319.
Choi JY, Park YS, Cho CH, Park YS, Shin SY, Song YG, Yong D, Lee K, Kim JM. Synergic in-vitro activity of imipenem and sulbactam against Acinetobacter baumannii. Clin Microbiol Infect. 2004;10(12):1098-101.
Choi JY, Kim CO, Park YS, Yoon HJ, Shin SY, Kim YK, Kim MS, Kim YA, Song YG, Yong D, Lee K, Kim JM. Comparison of efficacy of cefoperazone/sulbactam and imipenem/cilastatin for treatment of Acinetobacter bacteremia. Yonsei Med J. 2006;47(1):63-9.
Clinical Laboratory Standards Institute (CLSI). Methods for Dilution Antibacterial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition. Document M07-A10. Wayne, USA, 2015.
Clinical Laboratory Standards Institute (CLSI). Performance Standards for Antibacterial Disk Susceptibility Tests; Approved Standard, Twelfth Edition. Document M02-A12. Wayne, USA, 2015.
Clinical Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Supplement M100-S27. Wayne, USA, 2017.
Da Silva GJ, Domingues S. Insights on the horizontal gene transfer of carbapenemase determinants in the opportunistic pathogen Acinetobacter baumannii. Microorganisms. 2016;4(3):pii: E29.
Diene SM, Rolain JM. Carbapenemase genes and genetic platforms in Gram-negative bacilli: Enterobacteriaceae, Pseudomonas and Acinetobacter species. Clin Microbiol Infect. 2014;20(9):831-8.
Evans BA, Hamouda A, Towner KJ, Amyes SG. OXA-51-like beta-lactamases and their association with particular epidemic lineages of Acinetobacter baumannii. Clin Microbiol Infect. 2008;14(3):268-75.
Figueiredo S, Poirel L, Papa A, Koulourida V, Nordmann P. Overexpression of the naturally occurring blaOXA-51 gene in Acinetobacter baumannii mediated by novel insertion sequence ISAba9. Antimicrob Agents Chemother. 2009;53(9):4045-7.
Fishbain J, Peleg AY. Treatment of Acinetobacter infections. Clin Infect Dis. 2010;51(1):79-84.
Fritzenwanker M, Imirzalioglu C, Herold S, Wagenlehner FM, Zimmer KP and Chakraborty T. Treatment options for carbapenem-resistant gram-negative infections. Dtsch Arztebl Int. 2018;115(20-21):345-52.
Ghajavand H, Esfahani BN, Havaei SA, Moghim S, Fazeli H. Molecular identification of Acinetobacter baumannii isolated from intensive care units and their antimicrobial resistance patterns. Adv Biomed Res. 2015;24:110.
Handal R, Qunibi L, Sahouri I, Juhari M, Dawodi R, Marzouqa H, Hindiyeh M. Characterization of carbapenem-resistant Acinetobacter baumannii strains isolated from hospitalized patients in Palestine. Int J Microbiol. 2017;2017:8012104.
Higgins PG, Pérez-Llarena FJ, Zander E, Fernández A, Bou G, Seifert H. OXA-235, a novel class D ß-lactamase involved in resistance to carbapenems in Acinetobacter baumannii. Antimicrob Agents Chemother. 2013;57(5):2121-6.
Hou C, Yang F. Drug-resistant gene of blaOXA-23, blaOXA-24, blaOXA-51 and blaOXA-58 in Acinetobacter baumannii. Int J Clin Exp Med. 2015;8(8):13859-63.
Hu WS, Yao SM, Fung CP, Hsieh YP, Liu CP, Li JF. An OXA-66/OXA-51-like carbapenemase and possibly an efflux pump are associated with resistance to imipenem in Acinetobacter baumannii. Antimicrob Agents Chemother. 2007;51(11):3844-52.
Karam G, Chastre J, Wilcox MH, Vincent JL. Antibiotic strategies in the era of multidrug resistance. Crit Care. 2016;20(1):136.
Khodavandi A, Alizadeh F, Aala F, Sekawi Z, Chong PP. In vitro investigation of antifungal activity of allicin alone and in combination with azoles against Candida species. Mycopathologia. 2010;169(4):287-95.
Khodavandi A, Harmal NS, Alizadeh F, Scully OJ, Sidik SM, Othman F Sekawi Z, Ng KP, Chong PP. Comparison between allicin and fluconazole in Candida albicans biofilm inhibition and in suppression of HWP1 gene expression. Phytomedicine. 2011;19(1):56-63.
Lin MF, Lan CY. Antimicrobial resistance in Acinetobacter baumannii: from bench to bedside. World J Clin Cases. 2014;2(12):787-814.
Manchanda V, Sanchaita S, Singh N. Multidrug resistant Acinetobacter. J Glob Infect Dis. 2010;2(3):291-304.
McLeod SM, Shapiro AB, Moussa SH, Johnstone M, McLaughlin RE, de Jonge BLM, Miller AA. Frequency and mechanism of spontaneous resistance to sulbactam combined with the 2 novel ß-lactamase inhibitor ETX2514 in clinical isolates of Acinetobacter baumannii. Antimicrol Agents Chemother. 2018;62(2):pii:e01576-17.
Montero A, Ariza J, Corbella X, Doménech A, Cabellos C, Ayats J, Tubau F, Borraz C, Gudiol F. Antibiotic combinations for serious infections caused by carbapenem-resistant Acinetobacter baumannii in a mouse pneumonia model. J Antimicrob Chemother. 2004;54(6):1085-91.
Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA. Carbapenems: past, present, and future. Antimicrob Agents Chemother. 2011;55(11):4943-60.
Penwell WF, Shapiro AB, Giacobbe RA, Gu RF, Gao N, Thresher J, McLaughlin RE, Huband MD, DeJonge BL, Ehmann DE, Miller AA. Molecular mechanisms of sulbactam antibacterial activity and resistance determinants in Acinetobacter baumannii. Antimicrob Agents Chemother. 2015;59(3):1680-9.
Perez F, Hujer AM, Hujer KM, Decker BK, Rather PN, Bonomo RA. Global challenge of multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2007;51(10):471-84.
Poirel L, Nordmann P. Carbapenem resistance in Acinetobacter baumannii: mechanisms and epidemiology. Clin Microbiol Infect. 2006;12(9):826-36.
Safari M, Saidijam M, Bahador A, Jafari R, Alikhani MY. High prevalence of multidrug resistance and metallo-beta-lactamase (MBL) producing Acinetobacter baumannii isolated from patients in ICU wards, Hamadan, Iran J Res Health Sci. 2013;13(2):162-7.
Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101-8.
Spellberg B, Bonomo RA. Combination therapy for extreme drug-resistant Acinetobacter baumannii: ready for prime time? Crit Care Med. 2015;43(6):1332-4.
van der Zwaluw K, de Haan A, Pluister GN, Bootsma HJ, de Neeling AJ, Schouls LM. The carbapenem inactivation method (CIM), a simple and low-cost alternative for the Carba NP test to assess phenotypic carbapenemase activity in Gram-negative rods. PLOS One. 2015;10(3):e0123690.
Viehman JA, Nguyen MH, Doi Y. Treatment options for carbapenem-resistant and extensively drug-resistant Acinetobacter baumannii infections. Drugs 2014;74(12): 1315-33.
Walther-Rasmussen J, Hoiby N. OXA-type carbapenemases. J Antimicrob Chemother. 2006;57(3):373-83.
Wang YC, Kuo SC, Yang YS, Lee YT, Chiu CH, Chuang MF, Lin JC, Chang FY, Chen TL. Individual or combined effects of meropenem, imipenem, sulbactam, colistin, and tigecycline on biofilm-embedded Acinetobacter baumannii and biofilm architecture. Antimicrob Agents Chemother. 2016;60(8):4670-6.
Downloads
Published
Issue
Section
License
Copyright (c) 2022 Brazilian Journal of Pharmaceutical Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content of the journal, except where identified, is licensed under a Creative Commons attribution-type BY.
The on line journal has open and free access.
