Activity of a novel combination against multidrug-resistant nonfermenters: ceftazidime plus NXL104

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.