TY - JOUR
T1 - High prevalence of ArmA-16S rRNA methyltransferase among aminoglycoside-resistant Klebsiella pneumoniae bloodstream isolates
AU - Isler, Burcu
AU - Falconer, Caitlin
AU - Vatansever, Cansel
AU - Özer, Berna
AU - Çınar, Güle
AU - Aslan, Abdullah Tarık
AU - Forde, Brian
AU - Harris, Patrick
AU - Şimşek, Funda
AU - Tülek, Necla
AU - Demirkaya, Hamiyet
AU - Menekşe, Şirin
AU - Akalin, Halis
AU - Balkan, İlker İnanç
AU - Aydın, Mehtap
AU - Tigen, Elif Tükenmez
AU - Demir, Safiye Koçulu
AU - Kapmaz, Mahir
AU - Keske, Şiran
AU - Doğan, Özlem
AU - Arabacı, Çiğdem
AU - Yağcı, Serap
AU - Hazırolan, Gülşen
AU - Bakır, Veli Oğuzalp
AU - Gönen, Mehmet
AU - Saltoğlu, Neşe
AU - Azap, Alpay
AU - Azap, Özlem
AU - Akova, Murat
AU - Ergönül, Önder
AU - Can, Füsun
AU - Paterson, David L.
N1 - Publisher Copyright:
© The Authors.
PY - 2022
Y1 - 2022
N2 - Introduction. Aminoglycosides are used for the treatment of carbapenemase-producing Klebsiella pneumoniae (CPK) infections. 16S rRNA methyltransferases (RMTs) confer resistance to all aminoglycosides and are often cocarried with NDM. Hypothesis/Gap Statement. There is a dart of studies looking at the aminoglycoside resistance mechanisms for invasive CPK isolates, particularly in OXA-48 endemic settings. Aim. We aimed to determine the prevalence of RMTs and their association with beta lactamases and MLSTs amongst aminoglycoside-resistant CPK bloodstream isolates in an OXA-48 endemic setting. Methodology. CPK isolates (n=181), collected as part of a multicentre cohort study, were tested for amikacin, gentamicin and tobramycin susceptibility using custom-made sensititre plates (GN2XF, Thermo Fisher Scientific). All isolates were previously subjected to whole-genome sequencing. Carbapenemases, RMTs, MLSTs and plasmid incompatibility groups were detected on the assembled genomes. Results. Of the 181 isolates, 109(60%) were resistant to all three aminoglycosides, and 96 of 109(88%) aminoglycoside-resistant isolates carried an RMT (85 ArmA, 10 RmtC, 4 RmtF1; three isolates cocarried ArmA and RmtC). Main clonal types associated with ArmA were ST2096 (49/85, 58%) and ST14 (24/85, 28%), harbouring mainly OXA-232 and OXA-48 +NDM, respectively. RmtC was cocarried with NDM (5/10) on ST395, and NDM +OXA-48 or NDM +KPC (4/10) on ST14, ST15 and ST16. All RMT producers also carried CTX-M-15, and the majority cocarried SHV-106, TEM-150 and multiple other antibiotic resistance genes. The majority of the isolates harboured a combination of IncFIB, IncH and IncL/M type plasmids. Non-NDM producing isolates remained susceptible to ceftazidime-avibactam. Conclusion. Aminoglycoside resistance amongst CPK bloodstream isolates is extremely common and mainly driven by clonal spread of ArmA carried on ST2096 and ST14, associated with OXA-232 and OXA48 +NDM carriage, respectively.
AB - Introduction. Aminoglycosides are used for the treatment of carbapenemase-producing Klebsiella pneumoniae (CPK) infections. 16S rRNA methyltransferases (RMTs) confer resistance to all aminoglycosides and are often cocarried with NDM. Hypothesis/Gap Statement. There is a dart of studies looking at the aminoglycoside resistance mechanisms for invasive CPK isolates, particularly in OXA-48 endemic settings. Aim. We aimed to determine the prevalence of RMTs and their association with beta lactamases and MLSTs amongst aminoglycoside-resistant CPK bloodstream isolates in an OXA-48 endemic setting. Methodology. CPK isolates (n=181), collected as part of a multicentre cohort study, were tested for amikacin, gentamicin and tobramycin susceptibility using custom-made sensititre plates (GN2XF, Thermo Fisher Scientific). All isolates were previously subjected to whole-genome sequencing. Carbapenemases, RMTs, MLSTs and plasmid incompatibility groups were detected on the assembled genomes. Results. Of the 181 isolates, 109(60%) were resistant to all three aminoglycosides, and 96 of 109(88%) aminoglycoside-resistant isolates carried an RMT (85 ArmA, 10 RmtC, 4 RmtF1; three isolates cocarried ArmA and RmtC). Main clonal types associated with ArmA were ST2096 (49/85, 58%) and ST14 (24/85, 28%), harbouring mainly OXA-232 and OXA-48 +NDM, respectively. RmtC was cocarried with NDM (5/10) on ST395, and NDM +OXA-48 or NDM +KPC (4/10) on ST14, ST15 and ST16. All RMT producers also carried CTX-M-15, and the majority cocarried SHV-106, TEM-150 and multiple other antibiotic resistance genes. The majority of the isolates harboured a combination of IncFIB, IncH and IncL/M type plasmids. Non-NDM producing isolates remained susceptible to ceftazidime-avibactam. Conclusion. Aminoglycoside resistance amongst CPK bloodstream isolates is extremely common and mainly driven by clonal spread of ArmA carried on ST2096 and ST14, associated with OXA-232 and OXA48 +NDM carriage, respectively.
KW - 16S rRNA methyltransferase
KW - ArmA
KW - Klebsiella pneumoniae
KW - NDM
KW - OXA-232
KW - OXA-48
KW - aminoglycoside resistance
KW - bloodstream
KW - carbapenem-resistant
UR - https://www.scopus.com/pages/publications/85147460921
U2 - 10.1099/jmm.0.001629
DO - 10.1099/jmm.0.001629
M3 - Article
C2 - 36748503
AN - SCOPUS:85147460921
SN - 0022-2615
VL - 71
JO - Journal of Medical Microbiology
JF - Journal of Medical Microbiology
IS - 12
M1 - 001629
ER -