Gupta Aanchal, Malik Saquib, Kaminski Monica, Landman David, Quale John M
Infectious Diseases Division, SUNY Downstate Medical Center, Brooklyn, New York, USA.
Microb Drug Resist. 2022 Apr;28(4):419-424. doi: 10.1089/mdr.2021.0025.
Infections due to extended-spectrum β-lactamase (ESBL)-producing Enterobacterales are an increasingly common problem. For many of these infections, no oral treatment options are available. The activity of amoxicillin-clavulanate combined with ceftibuten or cefpodoxime was evaluated against a group of and clinical isolates possessing a variety of CTX-M- and SHV-type ESBLs; some possessed bla as well. In time-kill studies, the combination of subinhibitory concentrations of amoxicillin-clavulanate with ceftibuten was bactericidal and synergistic for all strains with an amoxicillin-clavulanate MIC ≤32 μg/mL, regardless of the type of ESBL and the cephalosporin minimal inhibitory concentration (MIC). The combination with cefpodoxime was also bactericidal and synergistic against all but one of these strains. These combinations were further tested against two strains of and one in a sepsis model using larvae. The combination of amoxicillin-clavulanate with ceftibuten demonstrated a synergistic survival benefit against all three strains. The combination with cefpodoxime also improved survival against the two strains, but not the strain. These findings support combining amoxicillin-clavulanate with ceftibuten, and possibly cefpodoxime, for the treatment of infections due to ESBL producers and suggest that having an amoxicillin-clavulanate MIC of 32 μg/mL or less may predict activity at clinically achievable concentrations. Clinical studies are warranted to further evaluate this therapeutic approach.
产超广谱β-内酰胺酶（ESBL）肠杆菌引起的感染是一个日益常见的问题。对于许多此类感染，没有口服治疗选择。评估了阿莫西林-克拉维酸联合头孢布烯或头孢泊肟对一组具有多种CTX-M型和SHV型ESBL的临床分离株的活性；有些还携带bla。在时间-杀菌研究中，亚抑菌浓度的阿莫西林-克拉维酸与头孢布烯的组合对所有阿莫西林-克拉维酸MIC≤32μg/mL的菌株均具有杀菌和协同作用，无论ESBL的类型和头孢菌素最低抑菌浓度（MIC）如何。与头孢泊肟的组合对除一株外的所有这些菌株也具有杀菌和协同作用。在使用幼虫的败血症模型中，对这两种组合进一步针对两株和一株进行了测试。阿莫西林-克拉维酸与头孢布烯的组合对所有三株菌株均显示出协同生存益处。与头孢泊肟的组合也提高了对两株菌株的生存率，但对菌株没有效果。这些发现支持将阿莫西林-克拉维酸与头孢布烯以及可能的头孢泊肟联合用于治疗ESBL产生菌引起的感染，并表明阿莫西林-克拉维酸MIC为32μg/mL或更低可能预测在临床可达到浓度下的活性。有必要进行临床研究以进一步评估这种治疗方法。
