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. A two-fold reduction in the MIC(90) of ceftazidime to 8 mg/L was noted in Pseudomonas aeruginosa isolates when combined with avibactam, whereas little effect of avibactam was noted on the MIC values of the test compounds when tested against Acinetobacter baumannii isolates. Avibactam had little effect on the excellent activity of ceftazidime, ceftaroline and aztreonam against Haemophilus influenzae. It had no impact on the in vitro activity of ceftazidime and ceftaroline against staphylococci and streptococci. This study demonstrates that addition of avibactam enhances the activities of ceftazidime, ceftaroline and aztreonam against Enterobacteriaceae and P. aeruginosa but not against A. baumannii.

Testa R ，Cantón R ，Giani T ，Morosini MI ，Nichols WW ，Seifert H ，Stefanik D ，Rossolini GM ，Nordmann P ... -  《-》

In vitro activity of ceftaroline-avibactam against gram-negative and gram-positive pathogens isolated from patients in Canadian hospitals from 2010 to 2012: results from the CANWARD surveillance study.

Karlowsky JA ，Adam HJ ，Baxter MR ，Lagacé-Wiens PR ，Walkty AJ ，Hoban DJ ，Zhanel GG ... -  《-》

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). Ceftazidime-avibactam, ceftaroline-avibactam ands aztreonam-avibactam were active against the strains with an extended-spectrum β-lactamase (ESBL) or AmpC enzymes, but combination with avibactam did not reduce β-lactam MICs against A. baumannii with OXA β-lactamases including carbapenemases, such as OXA-40 and -69.

Yoshizumi A ，Ishii Y ，Aoki K ，Testa R ，Nichols WW ，Tateda K ... -  《-》

In vitro activity of avibactam (NXL104) in combination with β-lactams against Gram-negative bacteria, including OXA-48 β-lactamase-producing Klebsiella pneumoniae.

The objective of this study was to investigate the in vitro antibacterial activity of avibactam (formerly NXL104) in combination with imipenem, cefepime or ceftazidime against Gram-negative bacteria. Bacterial isolates included: Pseudomonas aeruginosa harbouring PER-1 β-lactamase (n=14); Acinetobacter baumannii harbouring PER-1, OXA-51 and OXA-58 (n=20); carbapenem-non-susceptible Klebsiella pneumoniae (n=25) and Escherichia coli (n=1) harbouring OXA-48; carbapenem-non-susceptible E. coli (n=1) harbouring both IMP-1 metallo-β-lactamase and extended-spectrum β-lactamase (ESBL); carbapenem-non-susceptible Serratia marcescens (n=1); and carbapenem-susceptible E. coli (n=20) and K. pneumoniae isolates (n=12) with CTX-M-15 ESBL. Minimum inhibitory concentrations (MICs) of imipenem, cefepime and ceftazidime were determined in combination with 4 mg/L avibactam by the Clinical and Laboratory Standards Institute (CLSI) method on Mueller-Hinton agar. Imipenem/avibactam and ceftazidime/avibactam displayed limited potency against A. baumannii isolates, whereas cefepime/avibactam and ceftazidime/avibactam were active against P. aeruginosa. Klebsiella pneumoniae isolates with OXA-48 β-lactamase were resistant to imipenem [MIC for 90% of the organisms (MIC(90)) ≥4 mg/L]. MIC(90) values for the combination of avibactam 4 mg/L with imipenem, cefepime and ceftazidime were in the susceptible range for all strains (MIC(90)≤0.5mg/L). All E. coli and K. pneumoniae isolates with CTX-M-15 β-lactamase were inhibited at ≤1 mg/L for combinations with avibactam and 100% were susceptible by CLSI breakpoint criteria to imipenem, cefepime and ceftazidime. In conclusion, combinations of imipenem, cefepime and ceftazidime with avibactam may present a promising therapeutic strategy to treat infections due to K. pneumoniae with OXA-48 enzyme as well as K. pneumoniae and E. coli with CTX-M-15 enzyme.

Aktaş Z ，Kayacan C ，Oncul O 《-》

Avibactam reverts the ceftazidime MIC90 of European Gram-negative bacterial clinical isolates to the epidemiological cut-off value.

Flamm RK ，Stone GG ，Sader HS ，Jones RN ，Nichols WW ... -  《-》