In vitro susceptibility of characterized ß-lactamase-producing strains tested with avibactam combinations.

Avibactam, a broad-spectrum ß-lactamase inhibitor, was tested with ceftazidime, ceftaroline, or aztreonam against 57 well-characterized Gram-negative strains producing ß-lactamases from all molecular classes. Most strains were nonsusceptible to the ß-lactams alone. Against AmpC-, extended-spectrum ß-lactamase (ESBL)-, and KPC-producing Enterobacteriaceae or Pseudomonas aeruginosa, avibactam lowered ceftazidime, ceftaroline, or aztreonam MICs up to 2,048-fold, to ≤4 µg/ml. Aztreonam-avibactam MICs against a VIM-1 metallo-ß-lactamase-producing Enterobacter cloacae and a VIM-1/KPC-3-producing Escherichia coli isolate were 0.12 and 8 µg/ml, respectively.

Synthesis and antibacterial activity of 9-substituted minocycline derivatives.

A number of 9-acylamino and 9-sulfonylamino derivatives of minocycline have been synthesized for structure-activity relationship studies. These compounds showed activity against both tetracycline-susceptible and tetracycline-resistant strains. Many of the 9-sulfonylamino derivatives exhibited improved antibacterial activity against a number of tetracycline- and minocycline-resistant Gram-positive pathogens.