In Vitro Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Asia-Pacific Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

ABSTRACT

The in vitro activities of ceftazidime-avibactam and comparators against 9,149 isolates of Enterobacteriaceae and 2,038 isolates of Pseudomonas aeruginosa collected by 42 medical centers in nine countries in the Asia-Pacific region from 2012 to 2015 were determined as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance program. Antimicrobial susceptibility testing was conducted by Clinical and Laboratory Standards Institute (CLSI) broth microdilution, and isolate subset analysis was performed on the basis of the resistant phenotypes and β-lactamase content. Ceftazidime-avibactam demonstrated potent in vitro activity (MIC, ≤8 μg/ml) against all Enterobacteriaceae tested (99.0% susceptible) and was the most active against isolates that were metallo-β-lactamase (MBL) negative (99.8% susceptible). Against P. aeruginosa , 92.6% of all isolates and 96.1% of MBL-negative isolates were susceptible to ceftazidime-avibactam (MIC, ≤8 μg/ml). The rates of susceptibility to ceftazidime-avibactam ranged from 97.0% (Philippines) to 100% (Hong Kong, South Korea) for Enterobacteriaceae and from 83.1% (Thailand) to 100% (Hong Kong) among P. aeruginosa isolates, with lower susceptibilities being observed in countries where MBLs were more frequently encountered (Philippines, Thailand). Ceftazidime-avibactam inhibited 97.2 to 100% of Enterobacteriaceae isolates, per country, that carried serine β-lactamases, including extended-spectrum β-lactamases, AmpC cephalosporinases, and carbapenemases (KPC, GES, OXA-48-like). It also inhibited 91.3% of P. aeruginosa isolates that were carbapenem nonsusceptible in which no acquired β-lactamase was detected. Among MBL-negative Enterobacteriaceae isolates that were ceftazidime nonsusceptible, meropenem nonsusceptible, colistin resistant, and multidrug resistant, ceftazidime-avibactam inhibited 96.1, 87.7, 100, and 98.8% of isolates, respectively, and among MBL-negative P. aeruginosa isolates that were ceftazidime nonsusceptible, meropenem nonsusceptible, colistin resistant, and multidrug resistant, ceftazidime-avibactam inhibited 79.6, 83.6, 83.3, and 68.2% of isolates, respectively. Overall, clinical isolates of Enterobacteriaceae and P. aeruginosa collected in nine Asia-Pacific countries from 2012 to 2015 were highly susceptible to ceftazidime-avibactam.

Related collections

Most cited references 21

Record: found
Abstract: found
Article: not found

Emergence of Ceftazidime-Avibactam Resistance Due to Plasmid-Borne blaKPC-3 Mutations during Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections.

Ryan K. Shields, Liang Chen, Shaoji Cheng … (2017)

Ceftazidime-avibactam is a novel β-lactam/β-lactamase inhibitor with activity against carbapenem-resistant Enterobacteriaceae (CRE) that produce Klebsiella pneumoniae carbapenemase (KPC). We report the first cases of ceftazidime-avibactam resistance to develop during treatment of CRE infections and identify resistance mechanisms. Ceftazidime-avibactam-resistant K. pneumoniae emerged in three patients after ceftazidime-avibactam treatment for 10 to 19 days. Whole-genome sequencing (WGS) of longitudinal ceftazidime-avibactam-susceptible and -resistant K. pneumoniae isolates was used to identify potential resistance mechanisms. WGS identified mutations in plasmid-borne blaKPC-3, which were not present in baseline isolates. blaKPC-3 mutations emerged independently in isolates of a novel sequence type 258 sublineage and resulted in variant KPC-3 enzymes. The mutations were validated as resistance determinants by measuring MICs of ceftazidime-avibactam and other agents following targeted gene disruption in K. pneumoniae, plasmid transfer, and blaKPC cloning into competent Escherichia coli In rank order, the impact of KPC-3 variants on ceftazidime-avibactam MICs was as follows: D179Y/T243M double substitution > D179Y > V240G. Remarkably, mutations reduced meropenem MICs ≥4-fold from baseline, restoring susceptibility in K. pneumoniae from two patients. Cefepime and ceftriaxone MICs were also reduced ≥4-fold against D179Y/T243M and D179Y variant isolates, but susceptibility was not restored. Reverse transcription-PCR revealed that expression of blaKPC-3 encoding D179Y/T243M and D179Y variants was diminished compared to blaKPC-3 expression in baseline isolates. In conclusion, the development of resistance-conferring blaKPC-3 mutations in K. pneumoniae within 10 to 19 days of ceftazidime-avibactam exposure is troubling, but clinical impact may be ameliorated if carbapenem susceptibility is restored in certain isolates.

0 comments Cited 191 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Activities of NXL104 combinations with ceftazidime and aztreonam against carbapenemase-Producing Enterobacteriaceae.

Neil Woodford, David M. Livermore, Michel Doumith … (2010)

Combinations of NXL104 with ceftazidime and aztreonam were tested against carbapenem-resistant members of the Enterobacteriaceae. Ceftazidime-NXL104 was active against strains with the OXA-48 enzyme or with combinations of impermeability and an extended-spectrum β-lactamase (ESBL) or AmpC enzyme and also against most Klebsiella spp. with the KPC enzyme, but metallo-β-lactamase producers were resistant. Aztreonam-NXL104 was active against all carbapenemase producers at 4 and 4 μg/ml, including those with metallo-β-lactamases.

0 comments Cited 80 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Multiyear, Multinational Survey of the Incidence and Global Distribution of Metallo-β-Lactamase-Producing Enterobacteriaceae and Pseudomonas aeruginosa.

Krystyna Kazmierczak, Sharon Rabine, Meredith Hackel … (2016)

Metallo-β-lactamases (MBLs) hydrolyze all classes of β-lactams except monobactams and are not inhibited by classic serine β-lactamase inhibitors. Gram-negative pathogens isolated from patient infections were collected from 202 medical centers in 40 countries as part of a global surveillance study from 2012 to 2014. Carbapenem-nonsusceptible Enterobacteriaceae and Pseudomonas aeruginosa were characterized for bla genes encoding VIM, IMP, NDM, SPM, and GIM variants using PCR and sequencing. A total of 471 MBL-positive isolates included the following species (numbers of isolates are in parentheses): P. aeruginosa (308), Klebsiella spp. (85), Enterobacter spp. (39), Proteeae (16), Citrobacter freundii (12), Escherichia coli (6), and Serratia marcescens (5) and were submitted by sites from 34 countries. Of these, 69.6% were collected in 9 countries (numbers of isolates are in parentheses): Russia (72), Greece (61), Philippines (54), Venezuela (29), and Kuwait, Nigeria, Romania, South Africa, and Thailand (20 to 25 isolates each). Thirty-two different MBL variants were detected (14 VIM, 14 IMP, and 4 NDM enzymes). Seven novel MBL variants were encountered in the study, each differing from a previously reported variant by one amino acid substitution: VIM-42 (VIM-1 [V223I]), VIM-43 (VIM-4 [A24V]), VIM-44 (VIM-2 [K257N]), VIM-45 (VIM-2 [T35I]), IMP-48 (IMP-14 [I69T]), IMP-49 (IMP-18 [V49F]), and NDM-16 (NDM-1 [R264H]). The in vitro activities of all tested antibiotics against MBL-positive Enterobacteriaceae were significantly reduced with the exception of that of aztreonam-avibactam (MIC90, 0.5 to 1 μg/ml), whereas colistin was the most effective agent against MBL-positive P. aeruginosa isolates (>97% susceptible). Although the global percentage of isolates encoding MBLs remains relatively low, their detection in 12 species, 34 countries, and all regions participating in this surveillance study is concerning.