1887

Abstract

Purpose. The emergence of carbapenem resistance in non-baumannii Acinetobacter has increased in clinical settings worldwide. We investigated the prevalence and mechanisms of carbapenem resistance in A. pittii and A. nosocomialis Thai isolates.

Methodology. Acinetobacter calcoaceticus–Acinetobacter baumannii (Acb) complex isolates were identified by gyrB mulitplex PCR. Carbapenem susceptibilities were studied by the agar dilution method and carbapenemase genes were detected by multiplex PCR. Reductions of the outer membrane proteins (OMPs) were evaluated by SDS-PAGE. Overexpressions of efflux pumps were detected by using efflux pump inhibitors and RT-PCR.

Results. Of the 346 Acb isolates, 22 and 19 were A. pittii and A. nosocomialis, respectively. The carbapenem resistance rates were 22.7 % in A. pittii and 26.3 % in A. nosocomialis. Three carbapenem-resistant A. pittii carried bla OXA-23. One carbapenem-resistant A. pittii harboured bla OXA-58, while another isolate co-harboured bla OXA-58 and bla IMP-14a. bla OXA-58 was also found in three carbapenem-susceptible A. pittii. Five carbapenem-resistant A. nosocomialis carried bla OXA-23. Eighteen A. pittii isolates carried bla OXA-213-like. Reduced OMPs were found in carbapenem-resistant and -susceptible A. pittii carrying bla OXA-58, but were not detected in carbapenem-resistant A. nosocomialis isolates. Overexpression of adeE was found in carbapenem-resistant A. pittii. No efflux pump genes were present in carbapenem-resistant A. nosocomialis.

Conclusion. The major mechanisms of carbapenem resistance in A. pittii and A. nosocomialis were the production of OXA-23 and OXA-58. Overexpression of adeE played a role in carbapenem resistance in A. pittii. Since bla OXA-58 was found in carbapenem-susceptible A. pittii, using carbapenems in the treatment of A. pittii infection should be considered.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000845
2018-10-12
2024-12-03
Loading full text...

Full text loading...

/deliver/fulltext/jmm/67/12/1667.html?itemId=/content/journal/jmm/10.1099/jmm.0.000845&mimeType=html&fmt=ahah

References

  1. Harding CM, Hennon SW, Feldman MF. Uncovering the mechanisms of Acinetobacter baumannii virulence. Nat Rev Microbiol 2018; 16:91–102 [View Article][PubMed]
    [Google Scholar]
  2. Fitzpatrick MA, Ozer E, Bolon MK, Hauser AR. Influence of ACB complex genospecies on clinical outcomes in a U.S. hospital with high rates of multidrug resistance. J Infect 2015; 70:144–152 [View Article][PubMed]
    [Google Scholar]
  3. Zander E, Fernández-González A, Schleicher X, Dammhayn C, Kamolvit W et al. Worldwide dissemination of acquired carbapenem-hydrolysing class D β-lactamases in Acinetobacter spp. other than Acinetobacter baumannii. Int J Antimicrob Agents 2014; 43:375–377 [View Article][PubMed]
    [Google Scholar]
  4. Lin YC, Sheng WH, Chen YC, Chang SC, Hsia KC et al. Differences in carbapenem resistance genes among Acinetobacter baumannii, Acinetobacter genospecies 3 and Acinetobacter genospecies 13TU in Taiwan. Int J Antimicrob Agents 2010; 35:439–443 [View Article][PubMed]
    [Google Scholar]
  5. Teixeira AB, Martins AF, Barin J, Hermes DM, Pitt CP et al. First report of carbapenem-resistant Acinetobacter nosocomialis isolates harboring ISAba1-blaOXA-23 genes in Latin America. J Clin Microbiol 2013; 51:2739–2741 [View Article][PubMed]
    [Google Scholar]
  6. Park YK, Jung SI, Park KH, Kim SH, Ko KS. Characteristics of carbapenem-resistant Acinetobacter spp. other than Acinetobacter baumannii in South Korea. Int J Antimicrob Agents 2012; 39:81–85 [View Article][PubMed]
    [Google Scholar]
  7. Higgins PG, Lehmann M, Wisplinghoff H, Seifert H. gyrB multiplex PCR to differentiate between Acinetobacter calcoaceticus and Acinetobacter genomic species 3. J Clin Microbiol 2010; 48:4592–4594 [View Article][PubMed]
    [Google Scholar]
  8. Clinical and Laboratory Standards Institute Performance Standards for Antimicrobial Susceptibility Testing, 26th ed. M100S Wayne,PA: CLSI; 2016
    [Google Scholar]
  9. Higgins PG, Pérez-Llarena FJ, Zander E, Fernández A, Bou G et al. OXA-235, a novel class D β-lactamase involved in resistance to carbapenems in Acinetobacter baumannii. Antimicrob Agents Chemother 2013; 57:2121–2126 [View Article][PubMed]
    [Google Scholar]
  10. Kamolvit W, Higgins PG, Paterson DL, Seifert H. Multiplex PCR to detect the genes encoding naturally occurring oxacillinases in Acinetobacter spp. J Antimicrob Chemother 2014; 69:959–963 [View Article][PubMed]
    [Google Scholar]
  11. 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 [View Article][PubMed]
    [Google Scholar]
  12. Poirel L, Walsh TR, Cuvillier V, Nordmann P. Multiplex PCR for detection of acquired carbapenemase genes. Diagn Microbiol Infect Dis 2011; 70:119–123 [View Article][PubMed]
    [Google Scholar]
  13. Zander E, Chmielarczyk A, Heczko P, Seifert H, Higgins PG. Conversion of OXA-66 into OXA-82 in clinical Acinetobacter baumannii isolates and association with altered carbapenem susceptibility. J Antimicrob Chemother 2013; 68:308–311 [View Article][PubMed]
    [Google Scholar]
  14. Singkham-In U, Chatsuwan T. In vitro activities of carbapenems in combination with amikacin, colistin, or fosfomycin against carbapenem-resistant Acinetobacter baumannii clinical isolates. Diagn Microbiol Infect Dis 2018; 91:169–174 [View Article][PubMed]
    [Google Scholar]
  15. Chuang YC, Sheng WH, Li SY, Lin YC, Wang JT et al. Influence of genospecies of Acinetobacter baumannii complex on clinical outcomes of patients with acinetobacter bacteremia. Clin Infect Dis 2011; 52:352–360 [View Article][PubMed]
    [Google Scholar]
  16. Chusri S, Chongsuvivatwong V, Rivera JI, Silpapojakul K, Singkhamanan K et al. Clinical outcomes of hospital-acquired infection with Acinetobacter nosocomialis and Acinetobacter pittii. Antimicrob Agents Chemother 2014; 58:4172–4179 [View Article][PubMed]
    [Google Scholar]
  17. Koh TH, Tan TT, Khoo CT, Ng SY, Tan TY et al. Acinetobacter calcoaceticus-Acinetobacter baumannii complex species in clinical specimens in Singapore. Epidemiol Infect 2012; 140:535–538 [View Article][PubMed]
    [Google Scholar]
  18. Matsui M, Suzuki S, Yamane K, Suzuki M, Konda T et al. Distribution of carbapenem resistance determinants among epidemic and non-epidemic types of Acinetobacter species in Japan. J Med Microbiol 2014; 63:870–877 [View Article][PubMed]
    [Google Scholar]
  19. Schleicher X, Higgins PG, Wisplinghoff H, Körber-Irrgang B, Kresken M et al. Molecular epidemiology of Acinetobacter baumannii and Acinetobacter nosocomialis in Germany over a 5-year period (2005−2009). Clin Microbiol Infect 2013; 19:737–742 [View Article][PubMed]
    [Google Scholar]
  20. Lee MJ, Jang SJ, Li XM, Park G, Kook JK et al. Comparison of rpoB gene sequencing, 16S rRNA gene sequencing, gyrB multiplex PCR, and the VITEK2 system for identification of Acinetobacter clinical isolates. Diagn Microbiol Infect Dis 2014; 78:29–34 [View Article][PubMed]
    [Google Scholar]
  21. National Antimicrobial Resistance Surveillence Center Thailand Percentage of susceptible Organisms Isolated from All Specimen, 74 hospitals, Jan - Dec 2017; 2017 http://narst.dmsc.moph.go.th/antibiograms/2017/12/Jan-Dec2017-All.pdf
  22. Thapa B, Tribuddharat C, Srifuengfung S, 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 2010; 41:625–635[PubMed]
    [Google Scholar]
  23. Higgins PG, Dammhayn C, Hackel M, Seifert H. Global spread of carbapenem-resistant Acinetobacter baumannii. J Antimicrob Chemother 2010; 65:233–238 [View Article][PubMed]
    [Google Scholar]
  24. Figueiredo S, Bonnin RA, Poirel L, Duranteau J, Nordmann P. Identification of the naturally occurring genes encoding carbapenem-hydrolysing oxacillinases from Acinetobacter haemolyticus, Acinetobacter johnsonii, and Acinetobacter calcoaceticus. Clin Microbiol Infect 2012; 18:907–913 [View Article][PubMed]
    [Google Scholar]
  25. Kouyama Y, Harada S, Ishii Y, Saga T, Yoshizumi A et al. Molecular characterization of carbapenem-non-susceptible Acinetobacter spp. in Japan: predominance of multidrug-resistant Acinetobacter baumannii clonal complex 92 and IMP-type metallo-β-lactamase-producing non-baumannii Acinetobacter species. J Infect Chemother 2012; 18:522–528 [View Article][PubMed]
    [Google Scholar]
  26. Fu Y, Jiang J, Zhou H, Jiang Y, Fu Y et al. Characterization of a novel plasmid type and various genetic contexts of bla OXA-58 in Acinetobacter spp. from multiple cities in China. PLoS One 2014; 9:e84680 [View Article][PubMed]
    [Google Scholar]
  27. Ji S, Chen Y, Ruan Z, Fu Y, Ji J et al. Prevalence of carbapenem-hydrolyzing class D β-lactamase genes in Acinetobacter spp. isolates in China. Eur J Clin Microbiol Infect Dis 2014; 33:989–997 [View Article][PubMed]
    [Google Scholar]
  28. Marti S, Sánchez-Céspedes J, Blasco MD, Ruiz M, Espinal P et al. Characterization of the carbapenem-hydrolyzing oxacillinase oxa-58 in an Acinetobacter genospecies 3 clinical isolate. Antimicrob Agents Chemother 2008; 52:2955–2958 [View Article][PubMed]
    [Google Scholar]
  29. Kamolvit W, Derrington P, Paterson DL, Sidjabat HE. A case of IMP-4-, OXA-421-, OXA-96-, and CARB-2-producing Acinetobacter pittii sequence type 119 in Australia. J Clin Microbiol 2015; 53:727–730 [View Article][PubMed]
    [Google Scholar]
  30. Ang GY, Yu CY, Cheong YM, Yin WF, Chan KG. Emergence of ST119 Acinetobacter pittii co-harbouring NDM-1 and OXA-58 in Malaysia. Int J Antimicrob Agents 2016; 47:168–169 [View Article][PubMed]
    [Google Scholar]
  31. Rimrang B, Chanawong A, Lulitanond A, Wilailuckana C, Charoensri N et al. Emergence of NDM-1- and IMP-14a-producing Enterobacteriaceae in Thailand. J Antimicrob Chemother 2012; 67:2626–2630 [View Article][PubMed]
    [Google Scholar]
  32. Chen TL, Chang WC, Kuo SC, Lee YT, Chen CP et al. 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 [View Article][PubMed]
    [Google Scholar]
  33. Evans BA, Hamouda A, Towner KJ, Amyes SG. Novel genetic context of multiple bla OXA-58 genes in Acinetobacter genospecies 3. J Antimicrob Chemother 2010; 65:1586–1588 [View Article][PubMed]
    [Google Scholar]
  34. Segal H, Garny S, Elisha BG. Is IS(ABA-1) customized for Acinetobacter?. FEMS Microbiol Lett 2005; 243:425–429 [View Article][PubMed]
    [Google Scholar]
  35. Mugnier PD, Poirel L, Naas T, Nordmann P. Worldwide dissemination of the blaOXA-23 carbapenemase gene of Acinetobacter baumannii. Emerg Infect Dis 2010; 16:35–40 [View Article][PubMed]
    [Google Scholar]
  36. Zhu L, Yan Z, Zhang Z, Zhou Q, Zhou J et al. Complete genome analysis of three Acinetobacter baumannii clinical isolates in China for insight into the diversification of drug resistance elements. PLoS One 2013; 8:e66584 [View Article][PubMed]
    [Google Scholar]
  37. Catel-Ferreira M, Coadou G, Molle V, Mugnier P, Nordmann P et al. Structure-function relationships of CarO, the carbapenem resistance-associated outer membrane protein of Acinetobacter baumannii. J Antimicrob Chemother 2011; 66:2053–2056 [View Article][PubMed]
    [Google Scholar]
  38. del Mar Tomás M, Beceiro A, Pérez A, Velasco D, Moure R et al. Cloning and functional analysis of the gene encoding the 33- to 36-kilodalton outer membrane protein associated with carbapenem resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 2005; 49:5172–5175 [View Article][PubMed]
    [Google Scholar]
  39. Dupont M, Pagès JM, Lafitte D, Siroy A, Bollet C. Identification of an OprD homologue in Acinetobacter baumannii. J Proteome Res 2005; 4:2386–2390 [View Article][PubMed]
    [Google Scholar]
  40. Smani Y, Pachón J. Loss of the OprD homologue protein in Acinetobacter baumannii: impact on carbapenem susceptibility. Antimicrob Agents Chemother 2013; 57:677 [View Article][PubMed]
    [Google Scholar]
  41. Fonseca EL, Scheidegger E, Freitas FS, Cipriano R, Vicente AC. Carbapenem-resistant Acinetobacter baumannii from Brazil: role of carO alleles expression and blaOXA-23 gene. BMC Microbiol 2013; 13:245 [View Article][PubMed]
    [Google Scholar]
  42. Coyne S, Courvalin P, Périchon B. Efflux-mediated antibiotic resistance in Acinetobacter spp. Antimicrob Agents Chemother 2011; 55:947–953 [View Article][PubMed]
    [Google Scholar]
  43. Chu YW, Chau SL, Houang ET. Presence of active efflux systems AdeABC, AdeDE and AdeXYZ in different Acinetobacter genomic DNA groups. J Med Microbiol 2006; 55:477–478 [View Article][PubMed]
    [Google Scholar]
/content/journal/jmm/10.1099/jmm.0.000845
Loading
/content/journal/jmm/10.1099/jmm.0.000845
Loading

Data & Media loading...

Supplements

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