Activity of the siderophore monobactam BAL30072 against multiresistant non-fermenters

Abstract

Background: We tested the activity of BAL30072, a novel siderophore monobactam, against multiresistant clinical isolates of Pseudomonas aeruginosa, Burkholderia cepacia group and Acinetobacter spp. and against laboratory P. aeruginosa strains with defined resistance mechanisms. Methods: MICs were determined on Mueller-Hinton agar supplemented with 2,2′ bipyridyl to induce iron transport; comparators were aztreonam, imipenem, meropenem and piperacillin/tazobactam. Results: BAL30072 was strikingly active against Acinetobacter baumannii, with 73% of 200 carbapenemase-producing isolates, most of them belonging to the UK-dominant OXA-23 clone 1 and SE clone lineages, susceptible at 1 mg/L and 89% at 8 mg/L. Resistance nevertheless was seen in a few representatives of these clones and appeared commoner among isolates representing other A. baumannii clones. Sixty-eight per cent of 50 B. cepacia complex isolates from cystic fibrosis (CF) were susceptible to BAL30072 at 1 mg/L and 78% at 8 mg/L, compared with only 22% susceptible to aztreonam at 8 mg/L. Activity against P. aeruginosa was good, though less dramatic, with 36% of 50 (mostly multiresistant) CF isolates susceptible at 8 mg/L, compared with 12% susceptible to aztreonam at 8 mg/L. BAL30072 was active against 11/19 metallo-β-lactamase-producing P. aeruginosa at 8 mg/L compared with 3/19 for aztreonam (12/19 versus 8/19 at 16 mg/L). Studies on P. aeruginosa mutants, isolates and transconjugants showed that BAL30072 was affected by efflux, AmpC and by a few uncommon acquired β-lactamases, including some extended-spectrum OXA types and PER-1. Conclusions: BAL30072 displayed impressive activity against many carbapenemase-producing A. baumannii, particularly against the two clones most prevalent in the UK, and also against B. cepacia complex isolates from CF; it was more active than aztreonam against P. aeruginosa. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.