Genetic characterization and in vitro activity of antimicrobial combinations of multidrug-resistant Acinetobacter baumannii from a general hospital in China

Chen,Fang; Wang,Ling; Wang,Min; Xie,Yixin; Xia,Xiaomeng; Li,Xianping; Liu,Yanhua; Cao,Wei; Zhang,Tingting; Li,Pengling; Yang,Min

doi:10.3892/ol.2017.7600

February-2018 Volume 15 Issue 2

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February-2018 Volume 15 Issue 2

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Article Open Access

Genetic characterization and in vitro activity of antimicrobial combinations of multidrug-resistant Acinetobacter baumannii from a general hospital in China

Authors:
- Fang Chen
- Ling Wang
- Min Wang
- Yixin Xie
- Xiaomeng Xia
- Xianping Li
- Yanhua Liu
- Wei Cao
- Tingting Zhang
- Pengling Li
- Min Yang
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Affiliations: Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China

Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 2305-2315
|
Published online on: December 13, 2017

https://doi.org/10.3892/ol.2017.7600
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Abstract

The present study aimed to develop a rational therapy based on the genetic epidemiology, molecular mechanism evaluation and in vitro antibiotic combinations activity in multidrug-resistant Acinetobacter baumannii (MDRAB). MDRAB was screened by the Kirby‑Bauer method. The random amplified polymorphic DNA technique was used to establish genetic fingerprinting, and a series of resistance genes were detected by polymerase chain reaction. Antimicrobial agents including amikacin (AK), cefoperazone/sulbactam (SCF I/II), meropenem (MEM), minocycline (MINO) and ciprofloxacin (CIP) were used to determine the minimum inhibitory concentrations (MICs) and interactions between antibiotics by the broth microdilution method and chequerboard assays. In total, 34 MDRAB strains were isolated and classified into 8 phenotypes A‑H, according to their general drug susceptibilities. A total of 4 major genotypes (I‑IV) were clustered at 60% a genotypic similarity threshold. High positive rates of β‑lactamase TEM‑1, topoisomerase IV, oxacillinase (OXA)‑23, AdeB family multidrug efflux RND transporter adeB, β‑lactamase AmpC, class 1 integrons (Int‑1), 16S rRNA methylase rmtA, phosphotransferase aph(3), 16S rRNA methyltransferase armA were presented to exceed 90%, acetylyltransferase aac(3)‑I, aac(6'‑I, ant(3'')‑I, 16S rRNA methylase rmtB, oxacillinase OXA‑24 and metallo‑β‑lactamase IMP‑5 genes demonstrated positive rates of 29.4‑85.29%, while adeRS two‑component system was not observed in any strain. MEM+SCF I or SCF II primarily exhibited synergistic effects. AK+SCF I, AK+SCF II, MINO+SCF I, MINO+SCF II, MINO+CIP and MINO+MEM primarily presented additive effects. AK+CIP demonstrated 70.59% antagonism. The antibacterial activity of SCF I was superior compared with that of SCF II. The results indicated the polyclonal genetic epidemiological trend of MDRAB in the Second Xiangya Hospital, and verified the complexity of genetic resistance. In addition, combinations suggested to be efficacious were MEM+SCF I and MEM+SCF II, which were more effective compared with other combinations for the management of MDRAB infection.

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1	Visca P, Seifert H and Towner KJ: Acinetobacter infection - an emerging threat to human health. IUBMB Life. 63:1048–1054. 2011. View Article : Google Scholar : PubMed/NCBI
2	Munoz-Price LS and Weinstein RA: Acinetobacter infection. N Engl J Med. 358:1271–1281. 2008. View Article : Google Scholar : PubMed/NCBI
3	Dent LL, Marshall DR, Pratap S and Hulette RB: Multidrug resistant Acinetobacter baumannii: A descriptive study in a city hospital. BMC Infect Dis. 10:1962010. View Article : Google Scholar : PubMed/NCBI
4	Principe L, D'Arezzo S, Capone A, Petrosillo N and Visca P: In vitro activity of tigecycline in combination with various antimicrobials against multidrug resistant Acinetobacter baumannii. Ann Clin Microbiol Antimicrob. 8:182009. View Article : Google Scholar : PubMed/NCBI
5	Lim TP, Tan TY, Lee W, Sasikala S, Tan TT, Hsu LY and Kwa AL: In-vitro activity of polymyxin B, rifampicin, tigecycline alone and in combination against carbapenem-resistant Acinetobacter baumannii in Singapore. PLoS One. 6:e184852011. View Article : Google Scholar : PubMed/NCBI
6	Weng XB and Mi ZH: Phylogenetic analysis on pandrug-resistant Acinetobacter baumannii strains. Zhonghua Liu Xing Bing Xue Za Zhi. 32:948–949. 2011.(In Chinese). PubMed/NCBI
7	Zhao WS, Liu GY, Mi ZH and Zhang F: Coexistence of blaOXA-23 with armA and novel gyrA mutation in a pandrug-resistant Acinetobacter baumannii isolate from the blood of a patient with haematological disease in China. J Hosp Infect. 77:278–279. 2011. View Article : Google Scholar : PubMed/NCBI
8	Wen Y, Ouyang Z, Yu Y, Zhou X, Pei Y, Devreese B, Higgins PG and Zheng F: Mechanistic insight into how multidrug resistant Acinetobacter baumannii response regulator AdeR recognizes an intercistronic region. Nucleic Acids Res. 45:9773–9787. 2017. View Article : Google Scholar : PubMed/NCBI
9	Yang H, Huang L, Barnie PA, Su Z, Mi Z, Chen J, Aparna V, Kumar D and Xu H: Characterization and distribution of drug resistance associated β-lactamase, membrane porin and efflux pump genes in MDR A. Baumannii isolated from Zhenjiang, China. Int J Clin Exp Med. 8:15393–15402. 2015.PubMed/NCBI
10	Jiang W, Liu H, Zhong M, Yang YC, Xiao DW and Huang WF: Study on the resistant genes to carbapenems and epidemiological characterization of multidrug-resistant Acinetobacter baumannii isolates. Microb Drug Resist. 19:117–123. 2013. View Article : Google Scholar : PubMed/NCBI
11	Ramirez MS and Tolmasky ME: Aminoglycoside modifying enzymes. Drug Resist Updat. 13:151–171. 2010. View Article : Google Scholar : PubMed/NCBI
12	Petersen A, Guardabassi L, Dalsgaard A and Olsen JE: Class I integrons containing a dhfrl trimethoprim resistance gene cassette in aquatic Acinetobacter spp. FEMS Microbiol Lett. 182:73–76. 2000. View Article : Google Scholar : PubMed/NCBI
13	Azizi O, Shakibaie MR, Badmasti F, Modarresi F, Ramazanzadeh R, Mansouri S and Shahcheraghi F: Class 1 integrons in non-clonal multidrug-resistant Acinetobacter baumannii from Iran, description of the new blaIMP-55 allele in In1243. J Med Microbiol. 65:928–936. 2016. View Article : Google Scholar : PubMed/NCBI
14	Tada T, Miyoshi-Akiyama T, Kato Y, Ohmagari N, Takeshita N, Hung NV, Phuong DM, Thu TA, Binh NG, Anh NQ, et al: Emergence of 16S rRNA methylase-producing Acinetobacter baumannii and Pseudomonas aeruginosa isolates in hospitals in Vietnam. BMC Infect Dis. 13:2512013. View Article : Google Scholar : PubMed/NCBI
15	Lee JK, Lee YS, Park YK and Kim BS: Mutations in the gyrA and parC genes in ciprofloxacin-resistant clinical isolates of Acinetobacter baumannii in Korea. Microbiol Immunol. 49:647–653. 2005. View Article : Google Scholar : PubMed/NCBI
16	American Thoracic Society, . Infectious Diseases Society of America: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 171:388–416. 2005. View Article : Google Scholar : PubMed/NCBI
17	Clinical and Laboratory Standards Institute: Performance standards for antimicrobial susceptibility testing: Twenty-second informational supplement M100-S21. CLSI. 31:64–65. 2011.
18	Zhang T, Wang M, Xie Y, Li X, Dong Z, Liu Y, Wang L, Yang M, Song H, Cao H and Cao W: Active efflux pump adeB is involved in multidrug resistance of Acinetobacter baumannii induced by antibacterial agents. Exp Ther Med. 13:1538–1546. 2017. View Article : Google Scholar : PubMed/NCBI
19	Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J and Wheeler DL: GenBank. Nucleic Acids Res. 33:(Database Issue). D34–D38. 2005. View Article : Google Scholar : PubMed/NCBI
20	Daoud Z, Mansour N and Masri K: Synergistic combination of carbapenems and colistin against P. aeruginosa and A. baumannii. Open J Med Microbiol. 3:253–258. 2013. View Article : Google Scholar
21	Huang J, Chen EZ, Qu HP, Mao EQ, Zhu ZG, Ni YX, Han LZ and Tang YQ: Sources of multidrug-resistant Acinetobacter baumannii and its role in respiratory tract colonization and nosocomial pneumonia in intensive care unit patients. Chin Med J (Engl). 126:1826–1831. 2013.PubMed/NCBI
22	Xu T, Xia W, Rong G, Pan S, Huang P and Gu B: A 4-year surveillance of antimicrobial resistance patterns of Acinetobacter baumanni in a university-affiliated hospital in China. J Thorac Dis. 5:506–512. 2013.PubMed/NCBI
23	Koeleman JG, Stoof J, Biesmans DJ, Savelkoul PH and Vandenbroucke-Grauls CM: Comparison of amplified ribosomal DNA restriction analysis, random amplified polymorphic DNA analysis, and amplified fragment length polymorphism fingerprinting for identification of Acinetobacter genomic species and typing of Acinetobacter baumannii. J Clin Microbiol. 36:2522–2529. 1998.PubMed/NCBI
24	Fontana C, Favaro M, Minelli S, Bossa MC, Testore GP, Leonardis F, Natoli S and Favalli C: Acinetobacter baumannii in intensive care unit: A novel system to study clonal relationship among the isolates. BMC Infect Dis. 8:792008. View Article : Google Scholar : PubMed/NCBI
25	Niranjan DK, Singh NP, Manchanda V, Rai S and Kaur IR: Multiple carbapenem hydrolyzing genes in clinical isolates of Acinetobacter baumannii. Indian J Med Microbiol. 31:237–241. 2013. View Article : Google Scholar : PubMed/NCBI
26	Feizabadi MM, Fathollahzadeh B, Taherikalani M, Rasoolinejad M, Sadeghifard N, Aligholi M, Soroush S and Mohammadi-Yegane S: Antimicrobial susceptibility patterns and distribution of blaOXA genes among Acinetobacter spp. Isolated from patients at Tehran hospitals. Jpn J Infect Dis. 61:274–278. 2008.PubMed/NCBI
27	Thapa B, Tribuddharat C, Srifuengfung S and Dhiraputra C: High prevalence of bla(OXA)-23 in oligoclonal carbapenem-resistant Acinetobacter baumannii from Siriraj Hospital, Mahidol University, Bangkok, Thailand. Southeast Asian J Trop Med Public Health. 41:625–635. 2010.PubMed/NCBI
28	Chen Z, Liu W, Zhang Y, Li Y, Jian Z, Deng H, Zou M and Liu Y: Molecular epidemiology of carbapenem-resistant Acinetobacter spp. from XiangYa Hospital, in Hunan Province, China. J Basic Microbiol. 53:121–127. 2013. View Article : Google Scholar : PubMed/NCBI
29	Sung JY, Kwon KC, Cho HH and Koo SH: Antimicrobial resistance determinants in imipenem-nonsusceptible Acinetobacter calcoaceticus-baumannii complex isolated in Daejeon, Korea. Korean J Lab Med. 31:265–270. 2011. View Article : Google Scholar : PubMed/NCBI
30	Peymani A, Farajnia S, Nahaei MR, Sohrabi N, Abbasi L, Ansarin K and Azhari F: Prevalence of class 1 integron among multidrug-resistant Acinetobacter baumannii in Tabriz, northwest of Iran. Pol J Microbiol. 61:57–60. 2012.PubMed/NCBI
31	Farajnia S, Azhari F, Alikhani MY, Hosseini MK, Peymani A and Sohrabi N: Prevalence of PER and VEB type extended spectrum betalactamases among multidrug resistant acinetobacter baumannii Isolates in North-West of Iran. Iran J Basic Med Sci. 16:751–755. 2013.PubMed/NCBI
32	Yoon EJ, Courvalin P and Grillot-Courvalin C: RND-type efflux pumps in multidrug-resistant clinical isolates of Acinetobacter baumannii: Major role for AdeABC overexpression and AdeRS mutations. Antimicrob Agents Chemother. 57:2989–2995. 2013. View Article : Google Scholar : PubMed/NCBI
33	Jones RN, Barry AL, Packer RR, Gregory WW and Thornsberry C: In vitro antimicrobial spectrum, occurrence of synergy, and recommendations for dilution susceptibility testing concentrations of the cefoperazone-sulbactam combination. J Clin Microbiol. 25:1725–1729. 1987.PubMed/NCBI
34	Barry AL and Jones RN: Criteria for disk susceptibility tests and quality control guidelines for the cefoperazone-sulbactam combination. J Clin Microbiol. 26:13–17. 1988.PubMed/NCBI
35	Pei G, Mao Y and Sun Y: In vitro activity of minocycline alone and in combination with cefoperazone-sulbactam against carbapenem-resistant Acinetobacter baumannii. Microb Drug Resist. 18:574–577. 2012. View Article : Google Scholar : PubMed/NCBI
36	Deveci A, Coban AY, Acicbe O, Tanyel E, Yaman G and Durupinar B: In vitro effects of sulbactam combinations with different antibiotic groups against clinical Acinetobacter baumannii isolates. J Chemother. 24:247–252. 2012. View Article : Google Scholar : PubMed/NCBI