Skip to main content
Log in

Clonal dissemination of high-level gentamicin-resistant isolates of Enterococcus faecalis within a university hospital in southeastern Iran

Klonale Verbreitung von hochgradig gentamicinresistenten Isolaten von Enterococcus faecalis in einem Universitätsklinikum im Südosten des Iran

  • original article
  • Published:
Wiener Medizinische Wochenschrift Aims and scope Submit manuscript

Summary

Background

Combination of a cell wall-active antibiotic with an aminoglycoside confers a synergistic effect in the treatment of some severe enterococcal infections. Unfortunately, with the emergence of enterococci with high-level resistance to aminoglycosides, particularly to gentamicin, the efficacy of the synergistic combinations has decreased. In this study, high-level gentamicin-resistant (HLGR) isolates of enterococci and the diversity of the genes encoding aminoglycoside-modifying enzymes (AMEs) as well as putative clonal dissemination of HLGR isolates were investigated in a university hospital in southeastern Iran.

Methods

The minimum inhibitory concentration of gentamicin was determined and HLGR isolates were investigated for AME genes. Genetic similarity between isolates was analyzed using repetitive extragenic palindromic (rep)-Polymerase Chain Reaction (PCR) assay.

Results

Of 150 Enterococcus isolates, 62 isolates including Enterococcus faecalis (n = 46) and E. faecium (n = 16) were identified as HLGR. The most prevalent AME genes in both species were as follows: aph(3)-IIIa (n = 44), aac(6)-Ie-aph(2)-Ia (n = 36), and ant(4)-Ia (n = 15). The rep-PCR analysis showed clonality among E. faecalis isolates, so that 27 isolates were grouped in seven clusters representing similarity greater than 95%.

Conclusions

No link between AME determinants and clusters was found. Clonal spread of HLGR isolates of E. faecalis was found within our hospital. More rigorous recommendations are required to avoid dissemination of such resistant microorganisms in the hospital setting.

Zusammenfassung

Grundlagen

Die Kombination eines zellwandaktiven Antibiotikums mit einem Aminoglykosid bewirkt einen synergistischen Effekt bei der Behandlung einiger schwerer Enterokokkeninfektionen. Leider hat durch das Auftreten von Enterokokken mit einer hohen Resistenz gegen Aminoglykoside, insbesondere gegen Gentamicin, die Wirksamkeit der synergistischen Kombinationen abgenommen. In dieser Studie wurden gentamicinresistente (HLGR) Isolate von Enterokokken und die Vielfalt der Gene, die für aminoglycosidmodifizierende Enzyme (AME) kodieren, sowie die mutmaßliche klonale Verbreitung von HLGR-Isolaten in einem Universitätskrankenhaus im Südosten des Iran untersucht.

Methodik

Die minimale Hemmkonzentration von Gentamicin wurde bestimmt, und die HLGR-Isolate wurden für AME-Gene untersucht. Die genetische Ähnlichkeit zwischen den Isolaten wurde mit einem repetitiven palindromischen (rep‑)PCR(Polymerasekettenreaktion)-Assay analysiert.

Ergebnisse

Von 150 Enterococcus-Isolaten wurden 62 Isolate, darunter Enterococcus faecalis (n = 46) und E. faecium (n = 16), als HLGR identifiziert. Die häufigsten AME-Gene in beiden Spezies waren wie folgt: aph(3)-IIIa (n = 44), aac(6)-Ie-aph(2)-Ia (n = 36) und ant(4)-Ia (n = 15). Die rep-PCR-Analyse zeigte eine Klonalität unter den E.-faecalis-Isolaten, sodass 27 Isolate mit einer Ähnlichkeit von mehr als 95 % in gesamt 7 Clustern gruppiert werden konnten.

Schlussfolgerungen

Es wurde kein Zusammenhang zwischen AME-Determinanten und Clustern gefunden. In dem Krankenhaus der Autoren wurde eine klonale Ausbreitung von HLGR-Isolaten von E. faecalis festgestellt. Es sind strengere Empfehlungen erforderlich, um die Verbreitung solcher resistenter Mikroorganismen im Krankenhaus zu vermeiden.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Abbreviations

AACs/APHs:

acetyltransferases/phosphotransferases

AMEs:

aminoglycoside-modifying enzymes

ANTs:

adenyltransferases

APHs:

phosphotransferases

CLSI:

Clinical and Laboratory Standard Institute

HLGR:

high-level gentamicin-resistant

MIC:

minimum inhibitory concentration

rep-PCR:

repetitive extragenic palindromic

References

  1. Hollenbeck BL, Rice LB. Intrinsic and acquired resistance mechanisms in enterococcus. Virulence. 2012;3:421–569. https://doi.org/10.4161/viru.21282.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Arias CA, Contreras GA, Murray BE. Management of multidrug-resistant enterococcal infections. Clin Microbiol Infect. 2010;16:555–62. https://doi.org/10.1111/j.1469-0691.2010.03214.x.

    Article  CAS  PubMed  Google Scholar 

  3. Rosvoll TC, Lindstad BL, Lunde TM, et al. Increased high-level gentamicin resistance in invasive enterococcus faecium is associated with aac (6′) ie-aph (2 ″) Ia-encoding transferable megaplasmids hosted by major hospital-adapted lineages. FEMS Immunol Med Microbiol. 2012;66:166–76. https://doi.org/10.1111/j.1574-695X.2012.00997.x.

    Article  CAS  PubMed  Google Scholar 

  4. Behnood A, Farajnia S, Moaddab SR, et al. Prevalence of aac (6′)-Ie-aph (2 ″)-Ia resistance gene and its linkage to Tn5281 in enterococcus faecalis and enterococcus faecium isolates from Tabriz hospitals. Iran J Microbiol. 2013;5:203–8.

    PubMed  PubMed Central  Google Scholar 

  5. Emaneini M, Khoramian B, Jabalameli F, et al. Prevalence of high-level gentamicin-resistant enterococcus faecalis and enterococcus faecium in an Iranian hospital. J Prev Med Hyg. 2016;57:197–200.

    Google Scholar 

  6. Kuch A, Willems RJ, Werner G, et al. Insight into antimicrobial susceptibility and population structure of contemporary human enterococcus faecalis isolates from Europe. J Antimicrob Chemother. 2011;67:551–8. https://doi.org/10.1093/jac/dkr544.

    Article  CAS  PubMed  Google Scholar 

  7. Singh N, Léger MM, Campbell J, Short B, Campos JM. Control of vancomycin-resistant enterococci in the neonatal intensive care unit. Infect Control Hosp Epidemiol. 2005;26:646–9. https://doi.org/10.1086/502595.

    Article  PubMed  Google Scholar 

  8. Akpaka PE, Kissoon S, Jayaratne P. Molecular analysis of vancomycin-resistant enterococci isolated from regional hospitals in Trinidad and Tobago. Adv Med. 2016; https://doi.org/10.1155/2016/8762691.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Facklam RR, Collins MD. Identification of enterococcus species isolated from human infections by a conventional test scheme. J Clin Microbiol. 1989;27:731–4.

    Article  CAS  Google Scholar 

  10. Dutka-Malen S, Evers S, Courvalin P. Detection of glycopeptide resistance genotypes and identification to the species level of clinically relevant enterococci by PCR. J Clin Microbiol. 1995;33:24–7.

    Article  CAS  Google Scholar 

  11. Clinical and Labratory Standard Institute (CLSI). Performance standards for antimicrobial susceptibility testing. 28th ed. Wayne, PA: CLSI; 2015. pp. M100–S23.

    Google Scholar 

  12. Vakulenko SB, Donabedian SM, Voskresenskiy AM, et al. Multiplex PCR for detection of aminoglycoside resistance genes in enterococci. Antimicrob Agents Chemother. 2003;47:1423–6.

    Article  CAS  Google Scholar 

  13. Namdari H, DelVecchio V. Application of PCR for the characterization of enterococci. Clin Microbiol Newsl. 1998;20:91–4.

    Article  Google Scholar 

  14. Sreeja S, Sreenivasa Babu PR, Prathab AG. The prevalence and the characterization of the enterococcus species from various clinical samples in a tertiary care hospital. J Clin Diagn Res. 2012;6:1486–8. https://doi.org/10.7860/JCDR/2012/4560.2539.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Dadfarma N, Fooladi AA, Oskoui M, et al. High level of gentamicin resistance (HLGR) among enterococcus strains isolated from clinical specimens. J Infect Public Health. 2013;6:202–8. https://doi.org/10.1016/j.jiph.2013.01.001.

    Article  PubMed  Google Scholar 

  16. Padmasini E, Padmaraj R, Ramesh SS. High level aminoglycoside resistance and distribution of aminoglycoside resistant genes among clinical isolates of enterococcus species in Chennai, India. ScientificWorldJournal. 2014;2014:1–5. https://doi.org/10.1155/2014/329157.

    Article  CAS  Google Scholar 

  17. Amini F, Krimpour HA, Ghaderi M, et al. Prevalence of aminoglycoside resistance genes in enterococcus strains in Kermanshah, Iran. Iran J Med Sci. 2018;43:487–93.

    Google Scholar 

  18. Hasani A, Sharifi Y, Ghotaslou R, et al. Molecular screening of virulence genes in high-level gentamicin-resistant enterococcus faecalis and enterococcus faecium isolated from clinical specimens in northwest Iran. Indian J Med Microbiol. 2012;30:175–81. https://doi.org/10.4103/0255-0857.96687.

    Article  CAS  PubMed  Google Scholar 

  19. Li W, Li J, Wei Q, et al. Characterization of aminoglycoside resistance and virulence genes among enterococcus spp. isolated from a hospital in China. Int J Environ Res Public Health. 2015;12:3014–25. https://doi.org/10.3390/ijerph120303014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tomita H, Pierson C, Lim SK, et al. Possible connection between a widely disseminated conjugative gentamicin resistance (pMG1-like) plasmid and the emergence of vancomycin resistance in enterococcus faecium. J Clin Microbiol. 2002;40:3326–33. https://doi.org/10.1128/JCM.40.9.3326-3333.2002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Woegerbauer M, Zeinzinger J, Springer B, et al. Prevalence of the aminoglycoside phosphotransferase genes aph (3′)-IIIa and aph (3′)-IIa in escherichia coli, enterococcus faecalis, enterococcus faecium, pseudomonas aeruginosa, salmonella enterica subsp. enterica and staphylococcus aureus isolates in Austria. J Med Microbiol. 2014;63:210–7. https://doi.org/10.1099/jmm.0.065789-0.

    Article  CAS  PubMed  Google Scholar 

  22. Khani M, Fatollahzade M, Pajavand H, et al. Increasing prevalence of aminoglycoside-resistant enterococcus faecalis isolates due to the aac (6′)-aph (2″) gene: a therapeutic problem in Kermanshah, Iran. Jundishapur J Microbiol. 2016;9:e28923. https://doi.org/10.5812/jjm.28923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Niu H, Yu H, Hu T, et al. The prevalence of aminoglycoside-modifying enzyme and virulence genes among enterococci with high-level aminoglycoside resistance in Inner Mongolia, China. J Microbiol. 2016;47:691–6. https://doi.org/10.1016/j.bjm.2016.04.003.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the Student Research Committee of Kerman University of Medical Sciences, Kerman, Iran (Grant No: 96000503).

Author information

Authors and Affiliations

Authors

Contributions

F. Saffari conceived the study and participated in its design and execution, the data analysis, and writing the manuscript. H. Darehkordi contributed to sample collection and processing. R. Ahmadrajabi participated in design and execution of the study and writing the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Roya Ahmadrajabi.

Ethics declarations

Conflict of interest

F. Saffari, H. Darehkordi, and R. Ahmadrajabi declare that they have no competing interests.

Ethical standards

All procedures performed in studies involving human participants or on human tissue were in accordance with the ethical standards of the institutional and/or national research committee (ethics committee of Kerman University of Medical Sciences (IR.KMU.REC.1396.1599)) and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saffari, F., Darehkordi, H. & Ahmadrajabi, R. Clonal dissemination of high-level gentamicin-resistant isolates of Enterococcus faecalis within a university hospital in southeastern Iran. Wien Med Wochenschr 171, 18–23 (2021). https://doi.org/10.1007/s10354-019-00716-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10354-019-00716-2

Keywords

Schlüsselwörter

Navigation