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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.
Antimicrob Agents Chemother. 2018 12; 62(12)AA

Abstract

Enterobacteriaceae producing the Ambler class D OXA-48 carbapenemase, combined with additional resistance mechanisms, such as permeability defects or cocarriage of class A, B, or C β-lactamases, can become highly resistant to most β-lactams currently in use, including carbapenems. A total of 45,872 Enterobacteriaceae clinical isolates collected in 39 countries as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance study in 2012 to 2015 were tested for susceptibility to β-lactams and comparator agents using the Clinical and Laboratory Standards Institute broth microdilution methodology and screened for the presence of β-lactamases. The bla OXA-48 and bla OXA-48-like genes were detected in 333 isolates across 14 species of Enterobacteriaceae collected in 20 countries across the globe. Few agents tested were effective in vitro against the overall collection of OXA-48-producers (n = 265), with tigecycline (MIC90, 2 µg/ml; 92.5% susceptible), ceftazidime-avibactam (MIC90, 4 µg/ml; 92.5% susceptible), and aztreonam-avibactam (MIC90, 0.5 µg/ml; 99.6% of isolates with MIC ≤8 µg/ml) demonstrating the greatest activity. Similarly, colistin (MIC90, 1 µg/ml; 94.2% susceptible), tigecycline (MIC90, 2 µg/ml; 92.6% susceptible), ceftazidime-avibactam (MIC90, >128 µg/ml; 89.7% susceptible), and aztreonam-avibactam (MIC90, 4 µg/ml; 100% of isolates with MIC ≤8 µg/ml) were most active against OXA-48-like-positive isolates (n = 68). The in vitro activity of ceftazidime-avibactam was improved against the subset of metallo-β-lactamase (MBL)-negative, OXA-48- and OXA-48-like-positive isolates (99.2% and 100% susceptible, respectively). The data reported here support the continued investigation of ceftazidime-avibactam and aztreonam-avibactam for the treatment of infections caused by carbapenem-resistant Enterobacteriaceae carrying OXA-48 and OXA-48-like β-lactamases in combination with serine- or metallo-β-lactamases.

Authors+Show Affiliations

International Health Management Associates, Inc., Schaumburg, Illinois, USA kkazmierczak@ihmainc.com.AstraZeneca Pharmaceuticals LP, Waltham, Massachusetts, USA.AstraZeneca Pharmaceuticals LP, Waltham, Massachusetts, USA.AstraZeneca Pharmaceuticals LP, Waltham, Massachusetts, USA.International Health Management Associates, Inc., Schaumburg, Illinois, USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30249690

Citation

Kazmierczak, Krystyna M., 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." Antimicrobial Agents and Chemotherapy, vol. 62, no. 12, 2018.
Kazmierczak KM, Bradford PA, Stone GG, 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. Antimicrob Agents Chemother. 2018;62(12).
Kazmierczak, K. M., Bradford, P. A., Stone, G. G., de Jonge, B. L. M., & Sahm, D. F. (2018). 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. Antimicrobial Agents and Chemotherapy, 62(12). https://doi.org/10.1128/AAC.00592-18
Kazmierczak KM, 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. Antimicrob Agents Chemother. 2018;62(12) PubMed PMID: 30249690.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Kazmierczak,Krystyna M, AU - Bradford,Patricia A, AU - Stone,Gregory G, AU - de Jonge,Boudewijn L M, AU - Sahm,Daniel F, Y1 - 2018/11/26/ PY - 2018/03/26/received PY - 2018/09/07/accepted PY - 2018/9/27/pubmed PY - 2019/10/24/medline PY - 2018/9/26/entrez KW - Enterobacteriaceae KW - OXA-48 KW - aztreonam-avibactam KW - ceftazidime-avibactam KW - surveillance JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 62 IS - 12 N2 - Enterobacteriaceae producing the Ambler class D OXA-48 carbapenemase, combined with additional resistance mechanisms, such as permeability defects or cocarriage of class A, B, or C β-lactamases, can become highly resistant to most β-lactams currently in use, including carbapenems. A total of 45,872 Enterobacteriaceae clinical isolates collected in 39 countries as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance study in 2012 to 2015 were tested for susceptibility to β-lactams and comparator agents using the Clinical and Laboratory Standards Institute broth microdilution methodology and screened for the presence of β-lactamases. The bla OXA-48 and bla OXA-48-like genes were detected in 333 isolates across 14 species of Enterobacteriaceae collected in 20 countries across the globe. Few agents tested were effective in vitro against the overall collection of OXA-48-producers (n = 265), with tigecycline (MIC90, 2 µg/ml; 92.5% susceptible), ceftazidime-avibactam (MIC90, 4 µg/ml; 92.5% susceptible), and aztreonam-avibactam (MIC90, 0.5 µg/ml; 99.6% of isolates with MIC ≤8 µg/ml) demonstrating the greatest activity. Similarly, colistin (MIC90, 1 µg/ml; 94.2% susceptible), tigecycline (MIC90, 2 µg/ml; 92.6% susceptible), ceftazidime-avibactam (MIC90, >128 µg/ml; 89.7% susceptible), and aztreonam-avibactam (MIC90, 4 µg/ml; 100% of isolates with MIC ≤8 µg/ml) were most active against OXA-48-like-positive isolates (n = 68). The in vitro activity of ceftazidime-avibactam was improved against the subset of metallo-β-lactamase (MBL)-negative, OXA-48- and OXA-48-like-positive isolates (99.2% and 100% susceptible, respectively). The data reported here support the continued investigation of ceftazidime-avibactam and aztreonam-avibactam for the treatment of infections caused by carbapenem-resistant Enterobacteriaceae carrying OXA-48 and OXA-48-like β-lactamases in combination with serine- or metallo-β-lactamases. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/30249690/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_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=30249690 DB - PRIME DP - Unbound Medicine ER -