Johnston Brian D, Thuras Paul, Porter Stephen B, Anacker Melissa, VonBank Brittany, Snippes Vagnone Paula, Witwer Medora, Castanheira Mariana, Johnson James R
Minneapolis VA Health Care System, Minneapolis, Minnesota, USA
University of Minnesota, Minneapolis, Minnesota, USA.
Antimicrob Agents Chemother. 2020 Sep 21;64(10). doi: 10.1128/AAC.00797-20.
Emerging carbapenem resistance in , including sequence type 131 (ST131), the leading cause of extraintestinal infections globally, threatens therapeutic efficacy. Accordingly, we determined broth microdilution MICs for three distinctive newer agents, i.e., cefiderocol (CFDC), ceftazidime-avibactam (CZA), and eravacycline (ERV), plus 11 comparators, against 343 carbapenem-resistant (CR) clinical isolates, then compared susceptibility results with bacterial characteristics and region. The collection comprised 203 U.S. isolates (2002 to 2017) and 141 isolates from 17 countries in Europe, Latin America, and the Asia-West Pacific region (2003 to 2017). Isolates were characterized for phylogenetic group, resistance-associated sequence types (STs) and subsets thereof, and relevant beta-lactamase-encoding genes. CFDC, CZA, and ERV exhibited the highest percent susceptible (82% to 98%) after tigecycline (TGC) (99%); avibactam improved CZA's activity over that of CAZ (11% susceptible). Percent susceptible varied by phylogroup and ST for CFDC and CZA (greatest in phylogroups B2, D, and F, and in ST131, ST405, and ST648). Susceptibility also varied by resistance genotype, being higher with the carbapenemase (KPC) for CZA, lower with metallo-beta-lactamases for CFDC and CZA, and higher with the beta-lactamase CTX-M for ERV. Percent susceptible also varied by global region for CZA (lower in Asia-Pacific) and by U.S. region for ERV (lower in the South and Southeast). Although resistance to comparators often predicted reduced susceptibility to a primary agent (especially CFDC and CZA), even among comparator-resistant isolates the primary-agent-susceptible fraction usually exceeded 50%. These findings clarify the likely utility of CFDC, CZA, and ERV against CR in relation to multiple bacterial characteristics and geographical region.
碳青霉烯耐药性不断出现，包括序列类型131（ST131），它是全球肠外感染的主要原因，这对治疗效果构成了威胁。因此，我们测定了三种不同的新型药物，即头孢地尔（CFDC）、头孢他啶-阿维巴坦（CZA）和依拉环素（ERV），以及11种对照药物对343株耐碳青霉烯（CR）临床分离株的肉汤微量稀释最低抑菌浓度（MIC），然后将药敏结果与细菌特征和地区进行比较。该集合包括203株美国分离株（2002年至2017年）和141株来自欧洲、拉丁美洲和亚太地区17个国家的分离株（2003年至2017年）。对分离株进行系统发育群、耐药相关序列类型（STs）及其子集以及相关β-内酰胺酶编码基因的鉴定。CFDC、CZA和ERV在替加环素（TGC）（99%）之后表现出最高的敏感百分比（82%至98%）；阿维巴坦提高了CZA相对于头孢他啶（CAZ）的活性（11%敏感）。CFDC和CZA的敏感百分比因系统发育群和ST而异（在B2、D和F系统发育群以及ST131、ST405和ST648中最高）。药敏性也因耐药基因型而异，CZA对碳青霉烯酶（KPC）的药敏性较高，CFDC和CZA对金属β-内酰胺酶的药敏性较低，ERV对β-内酰胺酶CTX-M的药敏性较高。CZA的敏感百分比也因全球区域而异（在亚太地区较低），ERV的敏感百分比因美国地区而异（在南部和东南部较低）。虽然对对照药物的耐药性通常预示着对主要药物的敏感性降低（尤其是CFDC和CZA），但即使在对对照药物耐药的分离株中，对主要药物敏感的比例通常也超过50%。这些发现阐明了CFDC、CZA和ERV针对CR的潜在效用与多种细菌特征和地理区域的关系。
