Inmaculada López-Hernández1, Noemí Alonso2, Marta Fernández-Martínez3, Laura Zamorano4, Alba Rivera2, Antonio Oliver4, M Carmen Conejo5, Luis Martínez-Martínez6, Ferrán Navarro2, Alvaro Pascual7. 1. Intercentre Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen Macarena-Virgen del Rocío, Spain. Electronic address: inlopezh@us.es. 2. Santa Creu i Sant Pau Hospital, Barcelona, Spain. 3. University Hospital Marqués de Valdecilla, Santander, Spain. 4. Son Espases Hospital, Palma de Mallorca, Spain. 5. School of Medicine, University of Sevilla, Spain. 6. University Hospital Marqués de Valdecilla, Santander, Spain; Department of Molecular Biology, University of Cantabria, Santander, Spain. 7. Intercentre Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen Macarena-Virgen del Rocío, Spain; School of Medicine, University of Sevilla, Spain.
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.
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: Krisztina M Papp-Wallace; Andrew R Mack; Magdalena A Taracila; Robert A Bonomo Journal: Infect Dis Clin North Am Date: 2020-09-30 Impact factor: 5.982
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