In vitro activity of cefiderocol against ceftazidime-avibactam susceptible and resistant KPC-producing Enterobacterales: cross-resistance and synergistic effects.
Eur J Clin Microbiol Infect Dis
; 41(1): 63-70, 2022 Jan.
Article
em En
| MEDLINE
| ID: mdl-34462816
ABSTRACT
PURPOSE:
To assess the in vitro activity of cefiderocol (CFDC) against a collection of both ceftazidime-avibactam (CZA) susceptible and resistant KPC-producing Enterobacterales (KPC-EB) isolates. Secondly, to assess its synergistic activity in combination with different antibiotics.METHODS:
One hundred KPC-EB isolates were tested 60 CZA susceptible and 40 CZA resistant. Among them, 17 pairs of CZA susceptible and resistant KPC-producing Klebsiella pneumoniae (KPC-Kp) isolates were collected from 17 distinct patients before and after CZA treatment, respectively. CFDC susceptibility was evaluated by both broth microdilution (lyophilized panels; Sensititre; Thermo Fisher) and disk diffusion testing. Results were interpreted using EUCAST breakpoints. Synergistic activity of CFDC in combination with CZA, meropenem-vaborbactam, imipenem, and amikacin against six characterized KPC-Kp strains, before and after acquisition of CZA resistance, was evaluated using gradient diffusion strip crossing method.RESULTS:
CFDC resistance rate was significantly higher in CZA resistant EB subset than in the susceptible one (p < 0.001) 82.5% vs 6.7%. MIC50 and MIC90 values were 0.25 and 2 mg/L, 8 and 64 mg/L in CZA-susceptible and CZA-resistant subset, respectively. KPC-Kp isolates harboring KPC-D179Y or KPC-Δ242-GT-243 variants showed CFDC MICs ranging from 4 to 64 mg/L. CFDC showed in vitro synergistic effect mostly with CZA, against both CZA susceptible and resistant isolates, resulting in a synergy rate of 66.7%.CONCLUSIONS:
CZA resistance mechanisms in KPC-EB impair the in vitro activity of CFDC, often leading to co-resistance. CFDC in combination with the new ß-lactamases inhibitors might represent a strategy to enhance its activity.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Infecções por Klebsiella
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Ceftazidima
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Cefalosporinas
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Farmacorresistência Bacteriana
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Compostos Azabicíclicos
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Klebsiella pneumoniae
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Antibacterianos
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article