Activity of ceftazidime-avibactam against multidrug-resistance Enterobacteriaceae expressing combined mechanisms of resistance
Por:
Lopez-Hernandez, I, Alonso, N, Fernandez-Martinez, M, Zamorano, L, Rivera, A, Oliver, A, Conejo, MC, Martinez-Martinez, L, Navarro, F, Pascual, A
Publicada:
1 oct 2017
Resumen:
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. (C) 2016 Elsevier Espana, S.L.U. and Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica. All rights reserved.
Filiaciones:
Lopez-Hernandez, I:
Univ Hosp Virgen Macarena Virgen Rocio, Interctr Unit Infect Dis Microbiol & Prevent Med, Seville, Spain
Alonso, N:
Santa Creu & St Pau Hosp, Barcelona, Spain
Fernandez-Martinez, M:
Univ Hosp Marques de Valdecilla, Santander, Spain
Zamorano, L:
Son Espases Hosp, Palma De Mallorca, Spain
Rivera, A:
Santa Creu & St Pau Hosp, Barcelona, Spain
Oliver, A:
Son Espases Hosp, Palma De Mallorca, Spain
Conejo, MC:
Univ Seville, Sch Med, Seville, Spain
Martinez-Martinez, L:
Univ Hosp Marques de Valdecilla, Santander, Spain
Univ Cantabria, Dept Mol Biol, Santander, Spain
Navarro, F:
Santa Creu & St Pau Hosp, Barcelona, Spain
Pascual, A:
Univ Hosp Virgen Macarena Virgen Rocio, Interctr Unit Infect Dis Microbiol & Prevent Med, Seville, Spain
Univ Seville, Sch Med, Seville, Spain
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