Instituto Sacre Cour, Infectología Institucional SRL, Buenos Aires, Argentina.
Expert Rev Anti Infect Ther. 2011 Feb;9(2):173-6. doi: 10.1586/eri.10.173.
AmpC overexpression appears to be a significant mechanism of β-lactam resistance in Pseudomonas aeruginosa and other nonfermenter Gram-negatives. The article under review describes the in vitro activity of a novel combination ceftazidime plus NXL104, against ceftazidime-resistant Pseudomonas aeruginosa, Burkholderia cepacia complex and OXA carbapenemase-producing Acinetobacter baumannii. The study results show that NXL104 overcomes the ceftazidime resistance engendered by AmpC enzymes, even when these are completely derepressed. NXL104 has shown good activity against ESBL PER-1 in P. aeruginosa, as well as against most of the B. cepacia complex isolates from patients with cystic fibrosis. Nevertheless, NXL104 does not inhibit metallo-carbapenemases, which were excluded from this investigation, nor does it reverse resistance associated with oxacillin-type extended-spectrum β-lactamases in P. aeruginosa or with oxacillin-type carbapenemases in Acinetobacter spp. In the worldwide context of high rates of bacterial resistance, the combination of NXL104 with ceftazidime could represent a promising therapeutic strategy to treat infections due to AmpC-mediated resistance in P. aeruginosa, among other multidrug-resistant pathogens.
AmpC 过度表达似乎是铜绿假单胞菌和其他非发酵革兰氏阴性菌产生β-内酰胺耐药的重要机制。本文综述了新型头孢他啶加 NXL104 联合用药对头孢他啶耐药铜绿假单胞菌、洋葱伯克霍尔德菌复合群和产 OXA 碳青霉烯酶鲍曼不动杆菌的体外活性。研究结果表明，NXL104 克服了 AmpC 酶引起的头孢他啶耐药性，即使这些酶完全去阻遏。NXL104 对铜绿假单胞菌中的 ESBL PER-1 以及囊性纤维化患者的大多数洋葱伯克霍尔德菌复合群分离株表现出良好的活性。然而，NXL104 不抑制金属碳青霉烯酶，这些酶被排除在本研究之外，也不逆转铜绿假单胞菌中产 oxacillin 型扩展谱β-内酰胺酶和不动杆菌属中产 oxacillin 型碳青霉烯酶相关的耐药性。在细菌耐药率高的全球背景下，NXL104 与头孢他啶联合使用可能是一种有前途的治疗策略，可用于治疗铜绿假单胞菌中 AmpC 介导的耐药性引起的感染，以及其他多药耐药病原体。
