Activity of ceftazidime-avibactam against multidrug-resistance Enterobacteriaceae expressing combined mechanisms of resistance

作者：Lopez Hernandez Inmaculada^*; Alonso Noemi; Fernandez Martinez Marta; Zamorano Laura; Rivera Alba; Oliver Antonio; Carmen Conejo M; Martinez Martinez Luis; Navarro Ferran; Pascual Alvaro

来源：Enfermedades Infecciosas y Microbiologia Clinica, 2017, 35(8): 497-502.

DOI：10.1016/j.eimc.2016.09.013

• Ceftazidime
• Avibactam
• Enterobacteriaceae
• Porins
• AmpC
• Resistance

Introduction: Antimicrobial resistance in Enterobacteriaceae is increasing worldwide and is making treating infections caused by multidrug-resistant Enterobacteriaceae a challenge. The use of beta-lactam agents is compromised by microorganisms harboring extended-spectrum beta-lactamases (ESBLs) and other mechanisms of resistance. Avibactam is a non beta-lactam agent that inhibits clinically relevant beta-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 4 mg/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 beta-lactamases (ESBLs) and acquired AmpC beta-lactamases (AACBLs). Porin loss in IClebsiella 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.

• 出版日期2017-10