Inhibitory activity of avibactam against selected β-lactamases expressed in an isogenic Escherichia coli strain.

Avibactam restored the in-vitro antibacterial activity of ceftazidime, ceftaroline, and aztreonam against isogenic Escherichia coli expressing class A, class C, and class D β-lactamases. The enzymes included TEM and CTX-M extended spectrum β-lactamases, ACT, CMY and FOX AmpC-type enzymes, and carbapenemases including rarer KPC variants and OXA-139.

In vitro activity of ceftazidime, ceftaroline and aztreonam alone and in combination with avibactam against European Gram-negative and Gram-positive clinical isolates.

Recent clinical isolates of key Gram-negative and Gram-positive bacteria were collected in 2012 from hospitalised patients in medical centres in four European countries (France, Germany, Italy and Spain) and were tested using standard broth microdilution methodology to assess the impact of 4 mg/L avibactam on the in vitro activities of ceftazidime, ceftaroline and aztreonam. Against Enterobacteriaceae, addition of avibactam significantly enhanced the level of activity of these antimicrobials. MIC(90) values (minimum inhibitory concentration that inhibits 90% of the isolates) of ceftazidime, ceftaroline and aztreonam for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii and Morganella morganii were reduced up to 128-fold or greater when combined with avibactam.

Activities of ceftazidime, ceftaroline, and aztreonam alone and combined with avibactam against isogenic Escherichia coli strains expressing selected single β-lactamases.

Avibactam is a novel β-lactamase inhibitor that restores the activity of otherwise hydrolyzed β-lactams against Gram-negative bacteria expressing different classes of serine β-lactamases. In the last decade, β-lactam-avibactam combinations were tested against a variety of clinical isolates expressing multiple commonly encountered β-lactamases. Here, we analyzed isogenic Escherichia coli strains expressing selected single β-lactamase genes that were not previously tested or were not characterized in an isogenic background.

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

Avibactam, a broad-spectrum β-lactamase inhibitor, was tested with ceftazidime, ceftaroline, or aztreonam against 57 well-characterized Gram-negative strains producing β-lactamases from all molecular classes. Most strains were nonsusceptible to the β-lactams alone. Against AmpC-, extended-spectrum β-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.

In vitro susceptibility of characterized β-lactamase-producing Gram-negative bacteria isolated in Japan to ceftazidime-, ceftaroline-, and aztreonam-avibactam combinations.

Avibactam displays potent inhibition of extended-spectrum, AmpC, KPC and some OXA β-lactamases. We examined the combinations of avibactam with ceftazidime, ceftaroline and aztreonam by the broth microdilution method against Gram-negative bacteria harboring molecularly-characterized β-lactamase genes collected in Toho University, Japan. Bacterial isolates included: Ambler class A β-lactamase-producing Enterobacteriaceae (n = 26); class C β-lactamase-producing Enterobacteriaceae (n = 9) and class D β-lactamase-producing Acinetobacter baumannii (n = 9) and Enterobacteriaceae (n = 3).

In vitro activities of ceftazidime-avibactam and aztreonam-avibactam against 372 Gram-negative bacilli collected in 2011 and 2012 from 11 teaching hospitals in China.

Ceftazidime-avibactam, aztreonam-avibactam, and comparators were tested by reference broth microdilution against 372 nonrepetitive Gram-negative bacilli (346 unselected plus 26 selected meropenem-nonsusceptible Enterobacteriaceae isolates) collected from 11 teaching hospitals in China in 2011 and 2012. Meropenem-nonsusceptible isolates produced extended-spectrum β-lactamases (ESBLs; e.g.

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.