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Activity of ceftazidime-avibactam against multidrug-resistance Enterobacteriaceae expressing combined mechanisms of resistance.
Enferm Infecc Microbiol Clin. 2017 Oct; 35(8):499-504.EI

Abstract

INTRODUCTION

Antimicrobial resistance in Enterobacteriaceae is increasing worldwide and is making treating infections caused by multidrug-resistant Enterobacteriaceae a challenge. The use of β-lactam agents is compromised by microorganisms harboring extended-spectrum β-lactamases (ESBLs) and other mechanisms of resistance. Avibactam is a non β-lactam agent that inhibits clinically relevant β-lactamases, such as ESBL and AmpC. The ceftazidime-avibactam combination (CAZ-AVI) was recently approved for use in certain complicated infections, and may provide a therapeutic alternative for infections caused by these microorganisms.

METHODS

The in vitro activity of CAZ and CAZ-AVI (AVI at a fixed concentration of 4mg/L) was tested against 250 clinical isolates of Enterobacteriaceae using broth microdilution. EUCAST breakpoint criteria were used for CAZ, and FDA criteria for CAZ-AVI. Clinical isolates included bacteria producing extended-spectrum β-lactamases (ESBLs) and acquired AmpC β-lactamases (AACBLs). Porin loss in Klebsiella pneumoniae was also evaluated.

RESULTS

The combination of AVI with CAZ displayed excellent activity against clinical isolates of ESBL-producing Escherichia coli and Klebsiella pneumoniae, rendering all the ceftazidime-resistant isolates susceptible to ceftazidime. CAZ-AVI retained activity against porin-deficient isolates of K. pneumoniae producing ESBLs, AACBLs, or both, although MIC values were higher compared to porin-expressing isolates. CAZ-AVI rendered all the ceftazidime-resistant AACBL-producing Enterobacteriaceae tested susceptible to ceftazidime.

CONCLUSION

CAZ-AVI showed potent in vitro activity against clinical isolates of Enterobacteriaceae producing ESBLs and/or AACBLs, including K. pneumoniae with loss of porins.

Authors+Show Affiliations

Intercentre Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen Macarena-Virgen del Rocío, Spain. Electronic address: inlopezh@us.es.Santa Creu i Sant Pau Hospital, Barcelona, Spain.University Hospital Marqués de Valdecilla, Santander, Spain.Son Espases Hospital, Palma de Mallorca, Spain.Santa Creu i Sant Pau Hospital, Barcelona, Spain.Son Espases Hospital, Palma de Mallorca, Spain.School of Medicine, University of Sevilla, Spain.University Hospital Marqués de Valdecilla, Santander, Spain; Department of Molecular Biology, University of Cantabria, Santander, Spain.Santa Creu i Sant Pau Hospital, Barcelona, Spain.Intercentre Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen Macarena-Virgen del Rocío, Spain; School of Medicine, University of Sevilla, Spain.

Pub Type(s)

Comparative Study
Journal Article

Language

eng spa

PubMed ID

27887765

Citation

López-Hernández, Inmaculada, et al. "Activity of Ceftazidime-avibactam Against Multidrug-resistance Enterobacteriaceae Expressing Combined Mechanisms of Resistance." Enfermedades Infecciosas Y Microbiologia Clinica, vol. 35, no. 8, 2017, pp. 499-504.
López-Hernández I, Alonso N, Fernández-Martínez M, et al. Activity of ceftazidime-avibactam against multidrug-resistance Enterobacteriaceae expressing combined mechanisms of resistance. Enferm Infecc Microbiol Clin. 2017;35(8):499-504.
López-Hernández, I., Alonso, N., Fernández-Martínez, M., Zamorano, L., Rivera, A., Oliver, A., Conejo, M. C., Martínez-Martínez, L., Navarro, F., & Pascual, A. (2017). Activity of ceftazidime-avibactam against multidrug-resistance Enterobacteriaceae expressing combined mechanisms of resistance. Enfermedades Infecciosas Y Microbiologia Clinica, 35(8), 499-504. https://doi.org/10.1016/j.eimc.2016.09.013
López-Hernández I, et al. Activity of Ceftazidime-avibactam Against Multidrug-resistance Enterobacteriaceae Expressing Combined Mechanisms of Resistance. Enferm Infecc Microbiol Clin. 2017;35(8):499-504. PubMed PMID: 27887765.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activity of ceftazidime-avibactam against multidrug-resistance Enterobacteriaceae expressing combined mechanisms of resistance. AU - López-Hernández,Inmaculada, AU - Alonso,Noemí, AU - Fernández-Martínez,Marta, AU - Zamorano,Laura, AU - Rivera,Alba, AU - Oliver,Antonio, AU - Conejo,M Carmen, AU - Martínez-Martínez,Luis, AU - Navarro,Ferrán, AU - Pascual,Alvaro, Y1 - 2016/11/22/ PY - 2016/07/19/received PY - 2016/09/20/revised PY - 2016/09/21/accepted PY - 2016/11/27/pubmed PY - 2019/1/8/medline PY - 2016/11/27/entrez KW - AmpC KW - Avibactam KW - Ceftazidima KW - Ceftazidime KW - Enterobacteriaceae KW - Enterobacterias KW - Porinas KW - Porins KW - Resistance KW - Resistencia SP - 499 EP - 504 JF - Enfermedades infecciosas y microbiologia clinica JO - Enferm. Infecc. Microbiol. Clin. VL - 35 IS - 8 N2 - INTRODUCTION: Antimicrobial resistance in Enterobacteriaceae is increasing worldwide and is making treating infections caused by multidrug-resistant Enterobacteriaceae a challenge. The use of β-lactam agents is compromised by microorganisms harboring extended-spectrum β-lactamases (ESBLs) and other mechanisms of resistance. Avibactam is a non β-lactam agent that inhibits clinically relevant β-lactamases, such as ESBL and AmpC. The ceftazidime-avibactam combination (CAZ-AVI) was recently approved for use in certain complicated infections, and may provide a therapeutic alternative for infections caused by these microorganisms. METHODS: The in vitro activity of CAZ and CAZ-AVI (AVI at a fixed concentration of 4mg/L) was tested against 250 clinical isolates of Enterobacteriaceae using broth microdilution. EUCAST breakpoint criteria were used for CAZ, and FDA criteria for CAZ-AVI. Clinical isolates included bacteria producing extended-spectrum β-lactamases (ESBLs) and acquired AmpC β-lactamases (AACBLs). Porin loss in Klebsiella pneumoniae was also evaluated. RESULTS: The combination of AVI with CAZ displayed excellent activity against clinical isolates of ESBL-producing Escherichia coli and Klebsiella pneumoniae, rendering all the ceftazidime-resistant isolates susceptible to ceftazidime. CAZ-AVI retained activity against porin-deficient isolates of K. pneumoniae producing ESBLs, AACBLs, or both, although MIC values were higher compared to porin-expressing isolates. CAZ-AVI rendered all the ceftazidime-resistant AACBL-producing Enterobacteriaceae tested susceptible to ceftazidime. CONCLUSION: CAZ-AVI showed potent in vitro activity against clinical isolates of Enterobacteriaceae producing ESBLs and/or AACBLs, including K. pneumoniae with loss of porins. SN - 1578-1852 UR - https://www.unboundmedicine.com/medline/citation/27887765/Activity_of_ceftazidime_avibactam_against_multidrug_resistance_Enterobacteriaceae_expressing_combined_mechanisms_of_resistance_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0213-005X(16)30322-6 DB - PRIME DP - Unbound Medicine ER -