In vitro activity of ceftazidime/avibactam against isolates of carbapenem-non-susceptible Enterobacteriaceae collected during the INFORM global surveillance programme (2015–17)

Abstract Objectives To report data for ceftazidime/avibactam and comparators against meropenem-non-susceptible Enterobacteriaceae collected globally (excluding centres in the USA) from 2015 to 2017 as part of the International Network For Optimal Resistance Monitoring (INFORM) surveillance programme. Methods MICs and susceptibility were determined using EUCAST broth microdilution methodology and EUCAST breakpoints. Isolates were screened to detect genes encoding β-lactamases using multiplex PCR assays. MBL-positive isolates were those in which one or more of the IMP, VIM and/or NDM genes were detected. Results A total of 1460 meropenem-non-susceptible isolates were collected and, of the agents on the panel, susceptibility was highest to ceftazidime/avibactam, colistin and tigecycline [73.0%, 77.0% (1081/1403) and 78.1%, respectively]. Ceftazidime/avibactam was not active against MBL-positive isolates (n=367); these isolates showed the highest rates of susceptibility to colistin (92.1%, 303/329), tigecycline (71.9%) and amikacin (46.6%). A total of 394 isolates were resistant to ceftazidime/avibactam and, of the 369 isolates that were screened, 98.4% were found to carry a gene encoding an MBL enzyme. Among isolates that were identified as carbapenemase positive and MBL negative (n=910), susceptibility was highest to ceftazidime/avibactam (99.8%). Susceptibility was also highest to ceftazidime/avibactam among isolates that were carbapenemase negative and MBL negative (94/98, 95.9%). Conclusions These data highlight the need for continued surveillance of antimicrobial activity as well as the need for new antimicrobials to treat infections caused by meropenem-non-susceptible Enterobacteriaceae, for which the options are extremely limited.

[1]  K. Kazmierczak,et al.  In Vitro Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Latin American Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015 , 2018, Antimicrobial Agents and Chemotherapy.

[2]  K. Kazmierczak,et al.  In Vitro Activity of Ceftazidime-Avibactam and Aztreonam-Avibactam against OXA-48-Carrying Enterobacteriaceae Isolated as Part of the International Network for Optimal Resistance Monitoring (INFORM) Global Surveillance Program from 2012 to 2015 , 2018, Antimicrobial Agents and Chemotherapy.

[3]  S. Tiengrim,et al.  Collateral damage of using colistin in hospitalized patients on emergence of colistin-resistant Escherichia coli and Klebsiella pneumoniae colonization and infection , 2018, Antimicrobial Resistance & Infection Control.

[4]  K. Kazmierczak,et al.  In vitro activity of ceftazidime/avibactam against isolates of Enterobacteriaceae collected in European countries: INFORM global surveillance 2012–15 , 2018, The Journal of antimicrobial chemotherapy.

[5]  K. Kazmierczak,et al.  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 , 2018, Antimicrobial Agents and Chemotherapy.

[6]  E. Snesrud,et al.  Genomic Characterization of Nonclonal mcr-1-Positive Multidrug-Resistant Klebsiella pneumoniae from Clinical Samples in Thailand , 2018, Microbial drug resistance.

[7]  Z. Iqbal,et al.  The global distribution and spread of the mobilized colistin resistance gene mcr-1 , 2018, Nature Communications.

[8]  K. Bush.  Game Changers: New β-Lactamase Inhibitor Combinations Targeting Antibiotic Resistance in Gram-Negative Bacteria. , 2017, ACS infectious diseases.

[9]  Yanping Han,et al.  Mechanism for carbapenem resistance of clinical Enterobacteriaceae isolates. , 2017, Experimental and therapeutic medicine.

[10]  A. Friedrich,et al.  Expansion of KPC-producing Klebsiella pneumoniae with various mgrB mutations giving rise to colistin resistance: the role of ISL3 on plasmids. , 2017, International journal of antimicrobial agents.

[11]  Qi Zhao,et al.  Association Between Carbapenem Resistance and Mortality Among Adult, Hospitalized Patients With Serious Infections Due to Enterobacteriaceae: Results of a Systematic Literature Review and Meta-analysis , 2016, Open forum infectious diseases.

[12]  Prateek Shrivastava,et al.  World health organization releases global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics , 2018 .

[13]  M. Castanheira,et al.  Antimicrobial Activity of Ceftazidime-Avibactam Tested against Multidrug-Resistant Enterobacteriaceae and Pseudomonas aeruginosa Isolates from U.S. Medical Centers, 2013 to 2016 , 2017, Antimicrobial Agents and Chemotherapy.

[14]  G. Dantas,et al.  The rapid spread of carbapenem-resistant Enterobacteriaceae. , 2016, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[15]  J. Frère,et al.  Interaction of Avibactam with Class B Metallo-β-Lactamases , 2016, Antimicrobial Agents and Chemotherapy.

[16]  Ronald N. Jones,et al.  Changes in the Frequencies of β-Lactamase Genes among Enterobacteriaceae Isolates in U.S. Hospitals, 2012 to 2014: Activity of Ceftazidime-Avibactam Tested against β-Lactamase-Producing Isolates , 2016, Antimicrobial Agents and Chemotherapy.

[17]  K. Kazmierczak,et al.  In Vitro Susceptibility to Ceftazidime-Avibactam of Carbapenem-Nonsusceptible Enterobacteriaceae Isolates Collected during the INFORM Global Surveillance Study (2012 to 2014) , 2016, Antimicrobial Agents and Chemotherapy.

[18]  K. Kazmierczak,et al.  Activity of Ceftazidime-Avibactam against Extended-Spectrum- and AmpC β-Lactamase-Producing Enterobacteriaceae Collected in the INFORM Global Surveillance Study from 2012 to 2014 , 2016, Antimicrobial Agents and Chemotherapy.

[19]  K. Kazmierczak,et al.  Trends in Susceptibility of Escherichia coli from Intra-Abdominal Infections to Ertapenem and Comparators in the United States According to Data from the SMART Program, 2009 to 2013 , 2015, Antimicrobial Agents and Chemotherapy.

[20]  V. di Pilato,et al.  MgrB Inactivation Is a Common Mechanism of Colistin Resistance in KPC-Producing Klebsiella pneumoniae of Clinical Origin , 2014, Antimicrobial Agents and Chemotherapy.

[21]  M. Falagas,et al.  Deaths Attributable to Carbapenem-Resistant Enterobacteriaceae Infections , 2014, Emerging infectious diseases.

[22]  K. Bush.  Carbapenemases: Partners in crime. , 2013, Journal of global antimicrobial resistance.

[23]  R. Bonomo,et al.  Carbapenem-resistant Enterobacteriaceae: a review of treatment and outcomes. , 2013, Diagnostic microbiology and infectious disease.

[24]  J. Karlowsky,et al.  Ceftazidime-Avibactam: a Novel Cephalosporin/β-lactamase Inhibitor Combination , 2013, Drugs.

[25]  D. Ehmann,et al.  Avibactam is a covalent, reversible, non–β-lactam β-lactamase inhibitor , 2012, Proceedings of the National Academy of Sciences.

[26]  N. Woodford,et al.  Activities of NXL104 Combinations with Ceftazidime and Aztreonam against Carbapenemase-Producing Enterobacteriaceae , 2010, Antimicrobial Agents and Chemotherapy.

[27]  N. Woodford,et al.  Molecular mechanisms disrupting porin expression in ertapenem-resistant Klebsiella and Enterobacter spp. clinical isolates from the UK. , 2009, The Journal of antimicrobial chemotherapy.

[28]  Clinical laboratory testing and in vitro diagnostic test systems. Susceptibility testing of infectious agents and evaluation of performance of antimicrobial susceptibility test devices , 2022 .