Anes João, Martins Marta, Fanning Séamus
1 School of Public Health, Physiotherapy and Sports Science, UCD Centre for Food Safety, University College Dublin , Dublin, Ireland .
2 Institute for Global Food Security, Queen's University Belfast , Belfast, United Kingdom .
Microb Drug Resist. 2018 Jul 13. doi: 10.1089/mdr.2017.0386.
Eleven clinical Klebsiella pneumoniae fluoroquinolone-resistant isolates were tested to access the potential of adjuvant therapies to reduce antimicrobial resistance using fixed concentrations of the chemosensitizers chlorpromazine (CPZ), thioridazine (TZ), phenylalanine-arginine-β-naphthylamide (PAβN), and 1-(1-naphthylmethyl)-piperazine-(NMP) with varying concentrations of antimicrobial agents nalidixic acid (NAL), ciprofloxacin (CIP), moxifloxacin (MXF), tetracycline (TET), and chloramphenicol (CHL). Ethidium bromide dye was used together with the chemosensitizers to investigate permeabilization effects. NMP was assessed for its capacity to reduce the mass of biofilm alone and in combination with CIP and MXF. Of the selected chemosensitizers, NMP exhibited the greatest capacity to reverse resistance and inhibit efflux, based on the concentrations tested. Susceptibility to antimicrobial agents including (fluoro)quinolones, TET, and CHL were found to be increased in the presence of NMP, in a concentration-dependent manner. PAβN also demonstrated similar effects when combined with the chemosensitizers tested. In the case of half of the isolates studied, NMP alone reduced preformed biofilm biomass. Combinations of latter along with CIP or MXF were also found to reduce the mass of preformed biofilm, in the case of only some of the bacterial isolates. The capacity of NMP to reduce antimicrobial resistance could be of relevance as a strategy to limit bacterial colonization on abiotic surfaces.
对11株临床分离的耐氟喹诺酮肺炎克雷伯菌进行测试，以评估辅助治疗降低抗菌药物耐药性的潜力。使用固定浓度的化学增敏剂氯丙嗪（CPZ）、硫利达嗪（TZ）、苯丙氨酸 - 精氨酸 -β-萘酰胺（PAβN）和1-(1-萘甲基)-哌嗪（NMP），并搭配不同浓度的抗菌药物萘啶酸（NAL）、环丙沙星（CIP）、莫西沙星（MXF）、四环素（TET）和氯霉素（CHL）。溴化乙锭染料与化学增敏剂一起用于研究通透化作用。评估了NMP单独以及与CIP和MXF联合使用时减少生物膜量的能力。在所测试的浓度范围内，在所选择的化学增敏剂中，NMP表现出最大的逆转耐药性和抑制外排的能力。发现在存在NMP的情况下，包括（氟）喹诺酮类、TET和CHL在内的抗菌药物的敏感性以浓度依赖性方式增加。PAβN与所测试的化学增敏剂联合使用时也表现出类似的效果。在所研究的一半分离株中，单独使用NMP可减少预先形成的生物膜生物量。在仅部分细菌分离株中，后者与CIP或MXF的组合也被发现可减少预先形成的生物膜量。NMP降低抗菌药物耐药性的能力可能作为一种限制细菌在非生物表面定植的策略具有重要意义。
