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Modifiable Risk Factors for the Emergence of Ceftolozane-tazobactam Resistance.
Tamma, Pranita D; Beisken, Stephan; Bergman, Yehudit; Posch, Andreas E; Avdic, Edina; Sharara, Sima L; Cosgrove, Sara E; Simner, Patricia J.
Afiliación
  • Tamma PD; Johns Hopkins University School of Medicine, Department of Pediatrics, Division of Pediatric Infectious Diseases, Baltimore, Maryland USA.
  • Beisken S; Ares Genetics, Head of Bioinformatics & Analytics, Vienna, Austria.
  • Bergman Y; Johns Hopkins University School of Medicine, Department of Pathology, Baltimore, Maryland, USA.
  • Posch AE; Ares Genetics, Chief Executive Officer, Vienna, Austria.
  • Avdic E; Johns Hopkins Hospital, Department of Pharmacy, Baltimore, Maryland, USA.
  • Sharara SL; Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Cosgrove SE; Johns Hopkins University School of Medicine, Department of Medicine, Baltimore, Maryland, USA.
  • Simner PJ; Johns Hopkins University School of Medicine, Department of Pathology, Division of Medical Microbiology, Baltimore, Maryland, USA.
Clin Infect Dis ; 73(11): e4599-e4606, 2021 12 06.
Article en En | MEDLINE | ID: mdl-32881997
BACKGROUND: Ceftolozane-tazobactam (TOL-TAZ) affords broad coverage against Pseudomonas aeruginosa. Regrettably, TOL-TAZ resistance has been reported. We sought to identify modifiable risk factors that may reduce the emergence of TOL-TAZ resistance. METHODS: Twenty-eight consecutive patients infected with carbapenem-resistant P. aeruginosa isolates susceptible to TOL-TAZ, treated with ≥72 hours of TOL-TAZ , and with P. aeruginosa isolates available both before and after TOL-TAZ exposure between January 2018 and December 2019 in Baltimore, Maryland, were included. Cases were defined as patients with at least a 4-fold increase in P. aeruginosa TOL-TAZ MICs after exposure to TOL-TAZ. Independent risk factors for the emergence of TOL-TAZ resistance comparing cases and controls were investigated using logistic regression. Whole genome sequencing of paired isolates was used to identify mechanisms of resistance that emerged during TOL-TAZ therapy. RESULTS: Fourteen patients (50%) had P. aeruginosa isolates which developed at least a 4-fold increase in TOL-TAZ MICs(ie, cases). Cases were more likely to have inadequate source control (29% vs 0%, P = .04) and were less likely to receive TOL-TAZ as an extended 3-hour infusion (0% vs 29%; P = .04). Eighty-six percent of index isolates susceptible to ceftazidime-avibactam (CAZ-AVI) had subsequent P. aeruginosa isolates with high-level resistance to CAZ-AVI, after TOL-TAZ exposure and without any CAZ-AVI exposure. Common mutations identified in TOL-TAZ resistant isolates involved AmpC, a known binding site for both ceftolozane and ceftazidime, and DNA polymerase. CONCLUSIONS: Due to our small sample size, our results remain exploratory but forewarn of the potential emergence of TOL-TAZ resistance during therapy and suggest extending TOL-TAZ infusions may be protective. Larger studies are needed to investigate this association.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Pseudomonas Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Clin Infect Dis Asunto de la revista: DOENCAS TRANSMISSIVEIS Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Pseudomonas Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Clin Infect Dis Asunto de la revista: DOENCAS TRANSMISSIVEIS Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos