In-vitro activity of the monobactam, SQ 26,776, against Gram-negative bacteria and its stability to their -lactamases

Abstract
In-vitro activity of the new monobactam, Squibb 26,776 (SQ), was evaluated against Pseudomonas aeruginosa (95 strains), Kiebsiella aerogenes (108 strains) and 92 other Gram-negative bacteria. Activity was best against enterobacteriaceae: only occasional K. aero genes, Enierobacter cloacae and Citrobacter freundii were resistant to 1 mg/l of SQ. MICs against Ps. aeruginosa ranged from 0.25 to 32 mg/l and, against non-carbenicillinase-producing strains, correlated well with MICs of carbenicillin: implying that, for such strains identical, probably permeability, factors determine resistance or sensitivity to both these antibiotics. Other Pseudomonas spp. showed similar sensitivity to Ps. aeruginosa . Acinetobacter spp., Alcaligenes spp. and Flavobacterium spp. were generally rather resistant (MICs 4–64 mg/l). Bioassay indicated stability to plasmid-mediated TEM-1 and 2, OXA-1, 2 and 3 and PSE-1, 3 and 4 β -lactamases, also to the chromosomal β -lactamases of Ps. aeruginosa (Id enzyme) and Ent. cloacae (P-99 enzyme). Marginal instability to PSE-2 enzyme existed and this correlated with increased resistance to Ps. aeruginosa PU21 transconjugants producing this β -lactamase. TEM-1 and 2, OXA-3 and PSE-1 and 3 enzyme production did not increase SQ resistance of PU21. K-1 β -lactamase from K. aerogenes hydrolysed SQ. Typical K. aerogenes isolates, not overproducing this enzyme, remained sensitive to SQ but showed a three to four dilution inoculum effect between inoculum levels of 10 4 and 10 7 .