Changing of the #Frequencies of β-Lactamase #Genes Among #Enterobacteriaceae in #US #Hospitals (2012-2014): Activity of #Ceftazidime-Avibactam Tested against β-Lactamase-Producing Isolates (AAC, abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Changing of the Frequencies of β-Lactamase Genes Among Enterobacteriaceae in US Hospitals (2012-2014): Activity of Ceftazidime-Avibactam Tested against β-Lactamase-Producing Isolates

Mariana Castanheira1, Rodrigo E. Mendes1, Ronald N. Jones1 and Helio S. Sader1

Author Affiliations: 1JMI Laboratories, North Liberty, Iowa, US



Among 15,588 Enterobacteriaceae isolates collected in 63 United States (US) hospitals from 2012-2014, 2,129 (13.7%) displayed an extended spectrum β-lactamase (ESBL)-phenotype. These rates were similar over time (13.2-13.9%); however, differences among Escherichia coli (12.7/15.1% in 2012/2014; p=0.007) and Klebsiella pneumoniae (18.9/15.5%; p=0.006) were noted when comparing 2014 and 2012, respectively. Carbapenem-resistant Enterobacteriaceae (CRE; 2.3/1.8%) and carbapenem-resistant K. pneumoniae (6.8/5.1%; p=0.003) rates were lower in 2014 compared to prior years. Isolates carrying blaCTX-M-15-like were stable (42.1 to 42.4%), but a decrease among E. coli (59.1/49.7%; p=0.008) and an increase among K. pneumoniae (32.7/41.2%; p=0.022) in 2014 was observed. Isolates carrying blaKPC (304) decreased over the years (16.5/10.9%; p=0.008) mainly due to the decrease in K. pneumoniae harboring blaKPC (n=285; 35.6/28.4%; p=0.041) in hospitals of Mid-Atlantic and South Atlantic regions where these isolates were highly prevalent during 2012-2013. Isolates carrying blaCMY-2-like and blaCTX-M-14-like increased (8.2/11.9% and 9.1/12.9, respectively; p=0.04 for both), and those producing blaSHV ESBL decreased (24.9/12.7%; p<0.001) over the studied years, due to a decreased occurrence of these enzymes among K. pneumoniae. Other enzymes were detected in smaller numbers, including four K. pneumoniae isolates carrying blaNDM-1 metallo-β-lactamase (two in 2012 and two in 2014). Ceftazidime-avibactam, a recently approved β-lactamase inhibitor combination, was very active against the ESBL-phenotype isolates (MIC50/90, 0.12/1 μg/mL; 99.7% susceptible) and CRE strains (MIC50/90, 0.5/2 μg/mL; 98.5% susceptible) that displayed elevated MIC values for many comparator agents. In conclusion, significant changes were noted in the frequencies of isolates harbouring various β-lactamases among US hospitals between 2012-2014 that will require continued monitoring.



Contact Information: Mariana Castanheira, Ph.D., JMI Laboratories, 345 Beaver Kreek Ctr, Ste A, North Liberty, Iowa, 52317, US, Phone: 319-665-3370, Fax: 319-665-3371,

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Keywords: Research; Abstracts; Antibiotics; Drugs Resistance; Carbapenem; Enterobacteriaceae; USA; Avibactam; Ceftazidime.



An #Assessment of the In Vitro #Activity of #Ceftazidime-Avibactam Against MDR #Klebsiella spp. Collected in the #INFORM Global #Surveillance Study (2012-2014) (Antimicrob Agents Chemother., abstract)

Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

An Assessment of the In Vitro Activity of Ceftazidime-Avibactam Against Multi-Drug Resistant Klebsiella spp. Collected in the INFORM Global Surveillance Study (2012-2014)

M. Hackel1, K. Kazmierczak1#, D. Hoban1, D. Biedenbach1, S. Bouchillon1, B.L.M. DeJonge2 and G. Stone2

Author Affiliations: 1International Health Management Associates, Schaumburg, IL, USA – 2AstraZeneca Pharmaceuticals, Waltham, MA, USA



Increasing resistance in Gram-negative bacilli, including Klebsiella spp., has reduced the utility of broad-spectrum cephalosporins. Avibactam, a novel non-β-lactam β-lactamase inhibitor, protects β-lactams from hydrolysis by Gram-negative bacteria that produce extended-spectrum β-lactamases (ESBLs) and serine carbapenemases including Ambler class A and/or class C, and some class D enzymes. In this analysis, we report the in vitro activity of ceftazidime-avibactam and comparators against multi-drug resistant (MDR) Klebsiella spp. from the 2012–2014 INFORM surveillance study. Isolates collected from 176 sites were sent to a central laboratory for confirmatory identification and tested for susceptibility to ceftazidime-avibactam and comparator agents, including ceftazidime alone. A total of 2,821 of 10,998 (25.7%) Klebsiella spp. isolates were classified as MDR, based on resistance to three or more classes of antimicrobials. Among the MDR isolates, 99.4% had an extended-spectrum β-lactamase (ESBL) screen positive phenotype and 27.4% were not susceptible to meropenem as an example carbapenem. Ceftazidime-avibactam was highly active against MDR isolates, including ESBL-positive and serine carbapenemase-producing isolates, with MIC50/90 values of 0.5/2 μg/mL and 96.6% of all and ESBL-positive MDR isolates inhibited at the FDA breakpoint (MIC value ≤8 μg/mL). Ceftazidime-avibactam did not inhibit isolates producing class B enzymes (metallo-β-lactamases) either alone or in combination with other enzymes. These in vitro results support the continued investigation of ceftazidime-avibactam for the treatment of MDR Klebsiella spp.



#Corresponding author: Krystyna M. Kazmierczak, International Health Management Associates, Inc., 2122 Palmer Drive, Schaumburg, IL 60173, Phone: 1-847-303-5003, Fax: 1-847-303-5601, Email:

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Keywords: Research; Abstracts; Antibiotics; Drugs Resistance; Carbapenem; Klebsiella Penumoniae; Avibactam; Ceftazidime.