Karlowsky James A, Lob Sibylle H, Estabrook Mark A, Siddiqui Fakhar, DeRyke C Andrew, Young Katherine, Motyl Mary R, Sahm Daniel F
IHMA, Inc., Schaumburg, IL, USA.
Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
JAC Antimicrob Resist. 2023 Jun 28;5(3):dlad080. doi: 10.1093/jacamr/dlad080. eCollection 2023 Jun.
To determine susceptibility profiles and β-lactamase content for ceftolozane/tazobactam-resistant and imipenem/relebactam-resistant isolates collected in eight global regions during 2016-21.
Broth microdilution MICs were interpreted using CLSI breakpoints. PCR to identify β-lactamase genes or WGS was performed on selected isolate subsets.
Ceftolozane/tazobactam-resistant [from 0.6% (Australia/New Zealand) to 16.7% (Eastern Europe)] and imipenem/relebactam-resistant [from 1.3% (Australia/New Zealand) to 13.6% (Latin America)] varied by geographical region. Globally, 5.9% of isolates were both ceftolozane/tazobactam resistant and imipenem/relebactam resistant; 76% of these isolates carried MBLs. Most ceftolozane/tazobactam-resistant/imipenem/relebactam-susceptible isolates carried ESBLs (44%) or did not carry non-intrinsic (acquired) β-lactamases (49%); 95% of imipenem/relebactam-resistant/ceftolozane/tazobactam-susceptible isolates did not carry non-intrinsic β-lactamases. Isolates that carried indicators of strong PDC (-derived cephalosporinase) up-regulation without a mutation known to expand the spectrum of PDC, or non-intrinsic β-lactamases, showed an 8-fold increase in ceftolozane/tazobactam modal MIC; however, this rarely (3%) resulted in ceftolozane/tazobactam resistance. Isolates with a PDC mutation and an indicator for PDC upregulation were ceftolozane/tazobactam non-susceptible (MIC, ≥ 8 mg/L). MICs ranged widely (1 to >32 mg/L) for isolates with a PDC mutation and no positively identified indicator for PDC up-regulation. Imipenem/relebactam-resistant/ceftolozane/tazobactam-susceptible isolates without non-intrinsic β-lactamases frequently (91%) harboured genetic lesions implying OprD loss of function; however, this finding alone did not account for this phenotype. Among imipenem-non-susceptible isolates without non-intrinsic β-lactamases, implied OprD loss only shifted the distribution of imipenem/relebactam MICs up by 1-2 doubling dilutions, resulting in ∼10% imipenem/relebactam-resistant isolates.
with ceftolozane/tazobactam-resistant/imipenem/relebactam-susceptible and imipenem/relebactam-resistant/ceftolozane/tazobactam-susceptible phenotypes were uncommon and harboured diverse resistance determinants.
确定2016 - 2021年期间在全球八个地区收集的对头孢洛扎/他唑巴坦耐药和对亚胺培南/瑞来巴坦耐药的菌株的药敏谱和β-内酰胺酶含量。
采用美国临床和实验室标准协会（CLSI）的断点解释肉汤微量稀释法测定的最低抑菌浓度（MIC）。对选定的菌株亚组进行聚合酶链反应（PCR）以鉴定β-内酰胺酶基因或全基因组测序（WGS）。
对头孢洛扎/他唑巴坦耐药的比例[从0.6%（澳大利亚/新西兰）到16.7%（东欧）]和对亚胺培南/瑞来巴坦耐药的比例[从1.3%（澳大利亚/新西兰）到13.6%（拉丁美洲）]因地理区域而异。在全球范围内，5.9%的菌株对头孢洛扎/他唑巴坦耐药且对亚胺培南/瑞来巴坦耐药；其中76%的菌株携带金属β-内酰胺酶（MBL）。大多数对头孢洛扎/他唑巴坦耐药/对亚胺培南/瑞来巴坦敏感的菌株携带超广谱β-内酰胺酶（ESBL）（44%）或不携带非固有（获得性）β-内酰胺酶（49%）；95%对亚胺培南/瑞来巴坦耐药/对头孢洛扎/他唑巴坦敏感的菌株不携带非固有β-内酰胺酶。携带强诱导型AmpC（AmpC衍生的头孢菌素酶）上调指标但无已知可扩大AmpC谱的突变或非固有β-内酰胺酶的菌株，其头孢洛扎/他唑巴坦的模态MIC增加了8倍；然而，这很少（3%）导致对头孢洛扎/他唑巴坦耐药。具有AmpC突变和AmpC上调指标的菌株对头孢洛扎/他唑巴坦不敏感（MIC≥8 mg/L）。对于具有AmpC突变且未明确鉴定出AmpC上调阳性指标的菌株，MIC范围广泛（1至>32 mg/L）。不携带非固有β-内酰胺酶的对亚胺培南/瑞来巴坦耐药/对头孢洛扎/他唑巴坦敏感的菌株经常（91%）存在暗示外膜孔蛋白D（OprD）功能丧失的基因损伤；然而，仅这一发现并不能解释这种表型。在不携带非固有β-内酰胺酶的对亚胺培南不敏感的菌株中，暗示的OprD丧失仅使亚胺培南/瑞来巴坦MIC的分布向上移动1 - 2个稀释倍数，导致约10%的菌株对亚胺培南/瑞来巴坦耐药。
对头孢洛扎/他唑巴坦耐药/对亚胺培南/瑞来巴坦敏感和对亚胺培南/瑞来巴坦耐药/对头孢洛扎/他唑巴坦敏感的表型并不常见，并具有多种耐药决定因素。
