1887

Abstract

Purpose. The objective of the present study is to investigate the diverse resistance determinants, their association with insertion sequence mobile elements and predilection of a particular clone for such associations in Acinetobacter baumannii.

Methodology. Fifty-four consecutive isolates collected during 2011–2012 from a tertiary care hospital were subjected to susceptibility testing followed by PCR screening of commonly reported β-lactamases and 16S rRNA methyltransferase encoding genes. The integrity of resistance–nodulation–cell division efflux pump-related genes in their respective operons was also investigated.

Results. β-Lactamase genes such as bla ADC (100 %), bla OXA-23 (81 %), bla PER-1 (81 %), bla IMP-1 (31 %) and bla NDM-1 (15 %) were found to be present more frequently while bla VIM-2 and bla OXA-24 were not observed in our study population. ISAba1 was associated only with blaOXA-51-like like (30 %), bla OXA-23-like (55 %) and bla ADC-like (33 %). armA was found in 87 % of isolates and ISAba1 linked with one novel variant of ADC, namely bla ADC-82, which was identified to have 15 nucleotide differences with bla ADC-79, and this finding is of much significance. In many isolates, efflux pump genes were not intact, resulting in severely altered effluxing functions. For the first time, we have identified ISAba 1-mediated disruption of adeN among the isolates of ST 195, which would have led to overexpression of AdeIJK efflux pump causing elevated resistance. Multilocus sequence typing revealed the predominance of CC 92 (IC-II) and CC 447 clonal complexes.

Conclusion. High incidence of IC-II clones, novel resistance determinants (ADC-82) and elevated resistance mediated by ISAba1 reported here will be of enormous importance while assessing the emergence of extremely resistant A. baumannii in India.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000395
2017-03-07
2019-10-15
Loading full text...

Full text loading...

/deliver/fulltext/jmm/66/2/103.html?itemId=/content/journal/jmm/10.1099/jmm.0.000395&mimeType=html&fmt=ahah

References

  1. Dijkshoorn L, Nemec A, Seifert H. An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii. Nat Rev Microbiol 2007;5:939–951 [CrossRef][PubMed]
    [Google Scholar]
  2. Poirel L, Bonnin RA, Nordmann P. Genetic basis of antibiotic resistance in pathogenic Acinetobacter species. IUBMB Life 2011;63:1061–1067 [CrossRef][PubMed]
    [Google Scholar]
  3. Turton JF, Ward ME, Woodford N, Kaufmann ME, Pike R et al. The role of ISAba1 in expression of OXA carbapenemase genes in Acinetobacter baumannii. FEMS Microbiol Lett 2006;258:72–77 [CrossRef][PubMed]
    [Google Scholar]
  4. Hamidian M, Hancock DP, Hall RM. Horizontal transfer of an ISAba125-activated ampC gene between Acinetobacter baumannii strains leading to cephalosporin resistance. J Antimicrob Chemother 2013;68:244–245 [CrossRef][PubMed]
    [Google Scholar]
  5. Mishra S, Sen MR, Upadhyay S, Bhattacharjee A. Genetic linkage of blaNDM among nosocomial isolates of Acinetobacter baumannii from a tertiary referral hospital in northern India. Int J Antimicrob Agents 2013;41:452–456 [CrossRef][PubMed]
    [Google Scholar]
  6. 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;45:4054–4057 [CrossRef][PubMed]
    [Google Scholar]
  7. CLSI Performance Standards for Antimicrobial Susceptibility Testing: Twenty-Third Informational Supplement M100-S23 Wayne, PA: Clinical and Laboratory Standards Insitute; 2013
    [Google Scholar]
  8. Pachón-Ibáñez ME, Jiménez-Mejías ME, Pichardo C, Llanos AC, Pachón J. Activity of tigecycline (GAR-936) against Acinetobacter baumannii strains, including those resistant to imipenem. Antimicrob Agents Chemother 2004;48:4479–4481 [CrossRef][PubMed]
    [Google Scholar]
  9. Fernando DM, Xu W, Loewen PC, Zhanel GG, Kumar A. Triclosan can select for an AdeIJK-overexpressing mutant of Acinetobacter baumannii ATCC 17978 that displays reduced susceptibility to multiple antibiotics. Antimicrob Agents Chemother 2014;58:6424–6431 [CrossRef][PubMed]
    [Google Scholar]
  10. Hu WS, Yao SM, Fung CP, Hsieh YP, Liu CP et al. 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;51:3844–3852 [CrossRef][PubMed]
    [Google Scholar]
  11. Bartual SG, Seifert H, Hippler C, Luzon MA, Wisplinghoff H et al. Development of a multilocus sequence typing scheme for characterization of clinical isolates of Acinetobacter baumannii. J Clin Microbiol 2005;43:4382–4390 [CrossRef][PubMed]
    [Google Scholar]
  12. Saranathan R, Vasanth V, Vasanth T, Shabareesh PR, Shashikala P et al. Emergence of carbapenem non-susceptible multidrug resistant Acinetobacter baumannii strains of clonal complexes 103(B) and 92(B) harboring OXA-type carbapenemases and metallo-β-lactamases in Southern India. Microbiol Immunol 2015;59:277–284 [CrossRef][PubMed]
    [Google Scholar]
  13. Inchai J, Liwsrisakun C, Theerakittikul T, Chaiwarith R, Khositsakulchai W et al. Risk factors of multidrug-resistant, extensively drug-resistant and pandrug-resistant Acinetobacter baumannii ventilator-associated pneumonia in a Medical Intensive Care Unit of University Hospital in Thailand. J Infect Chemother 2015;21:570–574 [CrossRef][PubMed]
    [Google Scholar]
  14. Ranellou K, Kadlec K, Poulou A, Voulgari E, Vrioni G et al. Detection of Pseudomonas aeruginosa isolates of the international clonal complex 11 carrying the blaPER-1 extended-spectrum β-lactamase gene in Greece. J Antimicrob Chemother 2012;67:357–361 [CrossRef][PubMed]
    [Google Scholar]
  15. Zhou Z, du X, Wang L, Yang Q, Fu Y et al. Clinical carbapenem-resistant Acinetobacter baylyi strain coharboring blaSIM-1 and blaOXA-23 from China. Antimicrob Agents Chemother 2011;55:5347–5349 [CrossRef][PubMed]
    [Google Scholar]
  16. Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev 2008;21:538–582 [CrossRef][PubMed]
    [Google Scholar]
  17. Amudhan SM, Sekar U, Arunagiri K, Sekar B. OXA beta-lactamase-mediated carbapenem resistance in Acinetobacter baumannii. Indian J Med Microbiol 2011;29:269–274 [CrossRef][PubMed]
    [Google Scholar]
  18. He C, Xie Y, Zhang L, Kang M, Tao C et al. Increasing imipenem resistance and dissemination of the ISAba1-associated blaOXA-23 gene among Acinetobacter baumannii isolates in an intensive care unit. J Med Microbiol 2011;60:337–341 [CrossRef][PubMed]
    [Google Scholar]
  19. Villalón P, Valdezate S, Medina-Pascual MJ, Carrasco G, Vindel A et al. Epidemiology of the Acinetobacter-derived cephalosporinase, carbapenem-hydrolysing oxacillinase and metallo-β-lactamase genes, and of common insertion sequences, in epidemic clones of Acinetobacter baumannii from Spain. J Antimicrob Chemother 2013;68:550–553 [CrossRef][PubMed]
    [Google Scholar]
  20. Park YK, Choi JY, Jung SI, Park KH, Lee H et al. Two distinct clones of carbapenem-resistant Acinetobacter baumannii isolates from Korean hospitals. Diagn Microbiol Infect Dis 2009;64:389–395 [CrossRef][PubMed]
    [Google Scholar]
  21. Nie L, Lv Y, Yuan M, Hu X, Nie T et al. Genetic basis of high level aminoglycoside resistance in Acinetobacter baumannii from Beijing, China. Acta Pharm Sin B 2014;4:295–300 [CrossRef][PubMed]
    [Google Scholar]
  22. Bakour S, Touati A, Bachiri T, Sahli F, Tiouit D et al. First report of 16S rRNA methylase ArmA-producing Acinetobacter baumannii and rapid spread of metallo-β-lactamase NDM-1 in Algerian hospitals. J Infect Chemother 2014;20:696–701 [CrossRef][PubMed]
    [Google Scholar]
  23. Karthikeyan K, Thirunarayan MA, Krishnan P. Coexistence of blaOXA-23 with blaNDM-1 and armA in clinical isolates of Acinetobacter baumannii from India. J Antimicrob Chemother 2010;65:2253–2254 [CrossRef][PubMed]
    [Google Scholar]
  24. El-Sayed-Ahmed MA, Amin MA, Tawakol WM, Loucif L, Bakour S et al. High prevalence of bla(NDM-1) carbapenemase-encoding gene and 16S rRNA armA methyltransferase gene among Acinetobacter baumannii clinical isolates in Egypt. Antimicrob Agents Chemother 2015;59:3602–3605 [CrossRef][PubMed]
    [Google Scholar]
  25. Coyne S, Courvalin P, Périchon B. Efflux-mediated antibiotic resistance in Acinetobacter spp. Antimicrob Agents Chemother 2011;55:947–953 [CrossRef][PubMed]
    [Google Scholar]
  26. Rumbo C, Gato E, López M, Ruiz de Alegría C, Fernández-Cuenca F et al. Contribution of efflux pumps, porins, and β-lactamases to multidrug resistance in clinical isolates of Acinetobacter baumannii. Antimicrob Agents Chemother 2013;57:5247–5257 [CrossRef][PubMed]
    [Google Scholar]
  27. Yu Z, Reichheld SE, Savchenko A, Parkinson J, Davidson AR. A comprehensive analysis of structural and sequence conservation in the TetR family transcriptional regulators. J Mol Biol 2010;400:847–864 [CrossRef][PubMed]
    [Google Scholar]
  28. Stietz MS, Ramírez MS, Vilacoba E, Merkier AK, Limansky AS et al. Acinetobacter baumannii extensively drug resistant lineages in Buenos Aires hospitals differ from the international clones I–III. Infect Genet Evol 2013;14:294–301 [CrossRef][PubMed]
    [Google Scholar]
  29. Clímaco EC, Oliveira ML, Pitondo-Silva A, Oliveira MG, Medeiros M et al. Clonal complexes 104, 109 and 113 playing a major role in the dissemination of OXA-carbapenemase-producing Acinetobacter baumannii in Southeast Brazil. Infect Genet Evol 2013;19:127–133 [CrossRef][PubMed]
    [Google Scholar]
  30. Zhou Y, Wu X, Zhang X, Hu Y, Yang X et al. Genetic characterization of ST195 and ST365 carbapenem-resistant Acinetobacter baumannii harboring blaOXA-23 in Guangzhou, China. Microb Drug Resist 2015;21:386–390 [CrossRef][PubMed]
    [Google Scholar]
  31. Ruan Z, Chen Y, Jiang Y, Zhou H, Zhou Z et al. Wide distribution of CC92 carbapenem-resistant and OXA-23-producing Acinetobacter baumannii in multiple provinces of China. Int J Antimicrob Agents 2013;42:322–328 [CrossRef][PubMed]
    [Google Scholar]
  32. Lean SS, Yeo CC, Suhaili Z, Thong KL. Whole-genome analysis of an extensively drug-resistant clinical isolate of Acinetobacter baumannii AC12: insights into the mechanisms of resistance of an ST195 clone from Malaysia. Int J Antimicrob Agents 2015;45:178–182 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.000395
Loading
/content/journal/jmm/10.1099/jmm.0.000395
Loading

Data & Media loading...

Supplementary File 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error