Plambeck Lars, Fuchs Frieder, Sattler Janko, Hamprecht Axel
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Medical faculty and University Hospital of Cologne, Cologne, Germany.
JAC Antimicrob Resist. 2022 Jun 16;4(3):dlac059. doi: 10.1093/jacamr/dlac059. eCollection 2022 Jun.
With increasing resistance to common antibiotics the treatment of urinary tract infections has become challenging and alternative therapeutic options are needed. In the present study, we evaluate the activity of three older and less frequently used antibiotics against MDR Enterobacterales.
Susceptibility of mecillinam, temocillin and nitroxoline was assessed in Enterobacterales isolated from urinary specimens with elevated MICs of third-generation cephalosporins. Susceptibility was determined by the recommended reference MIC methods and additionally by disc diffusion. All isolates were characterized for common β-lactamases by phenotypic and molecular assays.
In total 394 Enterobacterales were included. The most common resistance mechanisms were ESBLs (= 273), AmpC (= 132), carbapenemases [= 12, including OXA-48-like (= 8), VIM (= 2), KPC (= 1) and NDM (= 1)] or others (= 2). Resistance was observed in 59% of isolates to ceftazidime, in 41% to piperacillin/tazobactam and in 54% to ciprofloxacin. In comparison, resistance was less frequent against mecillinam (15%), temocillin (13%) or nitroxoline (2%). Mecillinam showed higher activity in spp., and in OXA-48-like-producing isolates compared with temocillin, which was more active in and in ESBL-producing isolates. Activity of nitroxoline was high against all isolates, including carbapenemase-producing isolates. Correlation between disc diffusion and MIC methods was good for mecillinam and moderate for temocillin and nitroxoline.
Mecillinam, temocillin and nitroxoline show good to excellent activity in MDR Enterobacterales. The activity of mecillinam and temocillin was higher in certain species and restricted depending on β-lactamase production while nitroxoline showed universally high activity irrespective of species or β-lactamase present.
随着对常用抗生素耐药性的增加，尿路感染的治疗变得具有挑战性，需要替代治疗选择。在本研究中，我们评估了三种较老且较少使用的抗生素对多重耐药肠杆菌科细菌的活性。
对从第三代头孢菌素最低抑菌浓度（MIC）升高的尿液标本中分离出的肠杆菌科细菌评估美西林、替莫西林和硝呋太尔的敏感性。敏感性通过推荐的参考MIC方法测定，另外还通过纸片扩散法测定。通过表型和分子检测对所有分离株的常见β-内酰胺酶进行鉴定。
共纳入394株肠杆菌科细菌。最常见的耐药机制为超广谱β-内酰胺酶（ESBLs，273株）、AmpC（132株）、碳青霉烯酶[12株，包括OXA-48样酶（8株）、VIM（2株）、KPC（1株）和NDM（1株）]或其他（2株）。59%的分离株对头孢他啶耐药，41%对哌拉西林/他唑巴坦耐药，54%对环丙沙星耐药。相比之下，对美西林（15%）、替莫西林（13%）或硝呋太尔（2%）耐药的情况较少。与替莫西林相比，美西林在某些菌种以及产OXA-48样酶的分离株中显示出更高的活性，替莫西林在某些菌种和产ESBLs的分离株中活性更高。硝呋太尔对所有分离株，包括产碳青霉烯酶的分离株，活性都很高。纸片扩散法与MIC方法之间的相关性，美西林良好，替莫西林和硝呋太尔中等。
美西林、替莫西林和硝呋太尔对多重耐药肠杆菌科细菌显示出良好至优异的活性。美西林和替莫西林在某些菌种中的活性较高，且根据β-内酰胺酶的产生而受到限制，而硝呋太尔无论菌种或存在的β-内酰胺酶如何，均显示出普遍较高的活性。
