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.
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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
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Funding
This work was supported by the Student Research Committee of Kerman University of Medical Sciences, Kerman, Iran (Grant No: 96000503).
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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.
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F. Saffari, H. Darehkordi, and R. Ahmadrajabi declare that they have no competing interests.
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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.
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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
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DOI: https://doi.org/10.1007/s10354-019-00716-2
Keywords
- Minimum inhibitory concentration
- Aminoglycoside modifying enzyme
- Enterococcus faecalis
- High-level gentamicin-resistant
- Repetitive extragenic palindromic (rep)-PCR