<i>In Vitro</i>
            Activities of Ceftazidime-Avibactam and Aztreonam-Avibactam against 372 Gram-Negative Bacilli Collected in 2011 and 2012 from 11 Teaching Hospitals in China

Wang, Xiaojuan; Zhang, Feifei; Zhao, Chunjiang; Wang, Zhanwei; Nichols, Wright W.; Testa, R. T.; Li, Henan; Chen, Hongbin; He, Wenqiang; Wang, Qi; Wang, Hui

doi:10.1128/aac.02123-13

Cited by 81 publications

(63 citation statements)

References 17 publications

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“…The results in this study confirmed in vitro and in vivo studies of Enterobacteriaceae and P. aeruginosa that reported that ceftazidime-avibactam overcomes resistance attributable to ESBLs, plasmid-mediated AmpC ␤-lactamases, and carbapenemases with serine active sites (e.g., KPC), including multidrug-resistant isolates, but does not inhibit the growth of isolates producing metallo-␤-lactamases (5,6,(18)(19)(20)(21)(24)(25)(26)(27)). In the current study, 99.5% of all Enterobacteriaceae isolates tested were susceptible to ceftazidime-avibactam (Table 1), including the vast majority of ceftazidime-resistant and ESBLand AmpC ␤-lactamase-positive isolates.…”

Section: Discussionsupporting

confidence: 86%

“…ESBLs, plasmid-mediated AmpC ␤-lactamases, and carbapenemases pervade clinical isolates of Enterobacteriaceae worldwide (14)(15)(16)(17)(18)(19)(20)(21)(22). Geographic differences in ␤-lactamase composition and prevalence have been reported, require ongoing monitoring, and will continue to evolve over time under the influences of antimicrobial selective pressure and international travel (5,(14)(15)(16)(17)(18)(19)(20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

“…Geographic differences in ␤-lactamase composition and prevalence have been reported, require ongoing monitoring, and will continue to evolve over time under the influences of antimicrobial selective pressure and international travel (5,(14)(15)(16)(17)(18)(19)(20)(21)(22). Global surveillance studies consistently identify CTX-M-14, CTX-M-15, and SHV-12 to be the most prevalent ESBLs and CMY-2 as the most common plasmid-mediated AmpC ␤-lactamase currently circulating (2,3,15).…”

Section: Discussionmentioning

confidence: 99%

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Activity of Ceftazidime-Avibactam against Extended-Spectrum- and AmpC β-Lactamase-Producing Enterobacteriaceae Collected in the INFORM Global Surveillance Study from 2012 to 2014

Karlowsky¹,

Biedenbach²,

Kazmierczak³

et al. 2016

Antimicrob Agents Chemother

105

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The in vitro activity of ceftazidime-avibactam was evaluated against 34,062 isolates of Enterobacteriaceae from patients with intra-abdominal, urinary tract, skin and soft-tissue, lower respiratory tract, and blood infections collected in the INFORM (International Network For Optimal Resistance Monitoring) global surveillance study (176 medical center laboratories in 39 countries) in 2012 to 2014. Overall, 99.5% of Enterobacteriaceae isolates were susceptible to ceftazidime-avibactam using FDA approved breakpoints (susceptible MIC of <8 g/ml; resistant MIC of >16 g/ml). For individual species of the Enterobacteriaceae, the ceftazidime-avibactam MIC inhibiting >90% of isolates (MIC 90 ) ranged from 0.06 g/ml for Proteus species to 1 g/ml for Enterobacter spp. and Klebsiella pneumoniae. Carbapenem-susceptible isolates of Escherichia coli, K. pneumoniae, Klebsiella oxytoca, and Proteus mirabilis with a confirmed extended-spectrum ␤-lactamase (ESBL) phenotype, or a ceftazidime MIC of >16 g/ml if the ESBL phenotype was not confirmed by clavulanic acid inhibition, were characterized further to identify the presence of specific ESBL-and plasmid-mediated AmpC ␤-lactamase genes using a microarray-based assay and additional PCR assays. Ceftazidime-avibactam demonstrated potent activity against molecularly confirmed ESBL-producing (n ‫؍‬ 5,354; MIC 90 , 0.5 g/ml; 99.9% susceptible), plasmid-mediated AmpC-producing (n ‫؍‬ 246; MIC 90 , 0.5 g/ml; 100% susceptible), and ESBL-and AmpC-producing (n ‫؍‬ 152; MIC 90 , 1 g/ml; 100% susceptible) isolates of E. coli, K. pneumoniae, K. oxytoca, and P. mirabilis. We conclude that ceftazidime-avibactam demonstrates potent in vitro activity against globally collected clinical isolates of Enterobacteriaceae, including isolates producing ESBLs and AmpC ␤-lactamases.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Activity of Ceftazidime-Avibactam against Extended-Spectrum- and AmpC β-Lactamase-Producing Enterobacteriaceae Collected in the INFORM Global Surveillance Study from 2012 to 2014

Karlowsky¹,

Biedenbach²,

Kazmierczak³

et al. 2016

Antimicrob Agents Chemother

105

View full text Add to dashboard Cite

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“…It binds tightly to PBP3 in Gram-negative rods, with weaker binding to PBP1a, leading to filamentation followed by cell lysis (Sykes et al 1982). At the time that it was introduced into clinical practice, aztreonam was stable to hydrolysis by all of the common b-lactamases (Sykes et al 1982); the emergence of ESBLs and the serine carbapenemases has since rendered it less effective against multidrug-resistant blactamase-producing organisms (Wang et al 2014). However, the monobactam nucleus is not a good substrate for hydrolysis by MBLs, thus leading to a unique opportunity for this monobactam to be used in combination therapy with a serine b-lactamase inhibitor to treat infections caused by multi-b-lactamase-producing bacteria (see below) (Wang et al 2014).…”

Section: Monocyclic B-lactamsmentioning

confidence: 99%

β-Lactams and β-Lactamase Inhibitors: An Overview

Bush

Bradford

2016

Cold Spring Harb Perspect Med

713

587

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b-Lactams are the most widely used class of antibiotics. Since the discovery of benzylpenicillin in the 1920s, thousands of new penicillin derivatives and related b-lactam classes of cephalosporins, cephamycins, monobactams, and carbapenems have been discovered. Each new class of b-lactam has been developed either to increase the spectrum of activity to include additional bacterial species or to address specific resistance mechanisms that have arisen in the targeted bacterial population. Resistance to b-lactams is primarily because of bacterially produced b-lactamase enzymes that hydrolyze the b-lactam ring, thereby inactivating the drug. The newest effort to circumvent resistance is the development of novel broad-spectrum b-lactamase inhibitors that work against many problematic b-lactamases, including cephalosporinases and serine-based carbapenemases, which severely limit therapeutic options. This work provides a comprehensive overview of b-lactam antibiotics that are currently in use, as well as a look ahead to several new compounds that are in the development pipeline.

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“…The combination of aztreonam-avibactam, currently in development, is anticipated to have good activity against strains that harbor both NDM and other b-lactamases, as avibactam inhibits the activity of ESBL and AmpC enzymes. 69 In contrast, OXA-48 carbapenemases are relatively inactive against cephalosporins and carbapenems; thus, carbapenems may be effective against OXA-48-producing strains that do not contain other b-lactamases. It has been suggested that carbapenems should be included in treatment regimens for OXA-48 containing strains that have low meropenem or imipenem MICs.…”

Section: Treatment Implications Of Rapid Detection Of Crementioning

confidence: 99%

Clinical and laboratory considerations for the rapid detection of carbapenem-resistant Enterobacteriaceae

Banerjee

Humphries

2016

Virulence

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Carbapenem resistance among the Enterobacteriaceae has become a significant clinical and public health dilemma. Rapid administration of effective antimicrobials and implementation of supplemental infection control practices is required to both improve patient outcomes and limit the spread of these highly resistant organisms. However, carbapenem-resistant Enterobacteriaceae (CRE)-infected patients are predominantly identified by routine culture methods, which take days to perform. Rapid genomic and phenotypic methods are currently available to accelerate the identification of carbapenemaseproducing CRE. Effective use of these technologies is reliant on close collaboration between clinical microbiology, infection prevention, antimicrobial stewardship and infectious diseases specialists. This review discusses the performance characteristics of these technologies to date, and describes strategies for their optimal implementation.

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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

Cited by 81 publications

References 17 publications

Activity of Ceftazidime-Avibactam against Extended-Spectrum- and AmpC β-Lactamase-Producing Enterobacteriaceae Collected in the INFORM Global Surveillance Study from 2012 to 2014

Activity of Ceftazidime-Avibactam against Extended-Spectrum- and AmpC β-Lactamase-Producing Enterobacteriaceae Collected in the INFORM Global Surveillance Study from 2012 to 2014

β-Lactams and β-Lactamase Inhibitors: An Overview

Clinical and laboratory considerations for the rapid detection of carbapenem-resistant Enterobacteriaceae

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