Isler Burcu, Falconer Caitlin, Vatansever Cansel, Özer Berna, Çınar Güle, Aslan Abdullah Tarık, Forde Brian, Harris Patrick, Şimşek Funda, Tülek Necla, Demirkaya Hamiyet, Menekşe Şirin, Akalin Halis, Balkan İlker İnanç, Aydın Mehtap, Tigen Elif Tükenmez, Demir Safiye Koçulu, Kapmaz Mahir, Keske Şiran, Doğan Özlem, Arabacı Çiğdem, Yağcı Serap, Hazırolan Gülşen, Bakır Veli Oğuzalp, Gönen Mehmet, Saltoğlu Neşe, Azap Alpay, Azap Özlem, Akova Murat, Ergönül Önder, Can Füsun, Paterson David L
University of Queensland, Faculty of Medicine, UQ Centre for Clinical Research, Brisbane, Australia.
Infection Management Services, Princess Alexandra Hospital, Brisbane, Australia.
J Med Microbiol. 2022 Dec;71(12). doi: 10.1099/jmm.0.001629.
Aminoglycosides are used for the treatment of carbapenemase-producing (CPK) infections. 16S rRNA methyltransferases (RMTs) confer resistance to all aminoglycosides and are often cocarried with NDM. There is a dart of studies looking at the aminoglycoside resistance mechanisms for invasive CPK isolates, particularly in OXA-48 endemic settings. 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. CPK isolates (=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. 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. 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.
氨基糖苷类药物用于治疗产碳青霉烯酶（CPK）感染。16S rRNA甲基转移酶（RMTs）可使细菌对所有氨基糖苷类药物产生耐药性，且常与NDM共同携带。有大量研究关注侵袭性CPK分离株的氨基糖苷类耐药机制，尤其是在OXA - 48流行地区。我们旨在确定在OXA - 48流行地区，耐氨基糖苷类CPK血流感染分离株中RMTs的流行情况及其与β-内酰胺酶和多位点序列分型（MLSTs）的关联。作为一项多中心队列研究的一部分收集的CPK分离株（n = 181），使用定制的药敏板（GN2XF，赛默飞世尔科技公司）检测阿米卡星、庆大霉素和妥布霉素的敏感性。所有分离株之前均已进行全基因组测序。在组装好的基因组上检测碳青霉烯酶、RMTs、MLSTs和质粒不相容群。在181株分离株中，109株（60%）对所有三种氨基糖苷类药物耐药，109株耐氨基糖苷类药物的分离株中有96株（88%）携带RMT（85株携带ArmA，10株携带RmtC，4株携带RmtF1；3株同时携带ArmA和RmtC）。与ArmA相关的主要克隆型为ST2096（49/85，58%）和ST14（24/85，28%），分别主要携带OXA - 232和OXA - 48 + NDM。RmtC与NDM在ST395上共同携带（5/10），在ST14、ST15和ST16上与NDM + OXA - 48或NDM + KPC共同携带（4/10）。所有RMT产生菌还携带CTX - M - 15，大多数还共同携带SHV - 106、TEM - 150和多个其他抗生素耐药基因。大多数分离株携带IncFIB、IncH和IncL/M型质粒的组合。不产NDM的分离株对头孢他啶 - 阿维巴坦仍敏感。CPK血流感染分离株中的氨基糖苷类耐药极为常见，主要由ST2096和ST14上携带的ArmA的克隆传播驱动，分别与OXA - 232和OXA48 + NDM携带相关。
