Ceftazidime-avibactam as salvage therapy for infections caused by carbapenem-resistant organisms

Elizabeth Temkin, Julian Torre-Cisneros, Bojana Beovic, Natividad Benito, Maddalena Giannella, Raúl Gilarranz, Cameron Jeremiah, Belén Loeches, Isabel MacHuca, María José Jiménez-Martín, José Antonio Martínez, Marta Mora-Rillo, Enrique Navas, Michael Osthoff, Juan Carlos Pozo, Juan Carlos Ramos Ramos, Marina Rodriguez, Miguel Sánchez-García, Pierluigi Viale, Michel WolffYehuda Carmeli

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Abstract

© 2017 American Society for Microbiology. All Rights Reserved. Ceftazidime-avibactam (CAZ-AVI) is a recently approved β-lactam-β- lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twentyfive patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro. Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P = 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenemresistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited.
Original languageEnglish
Article numbere01964
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number2
DOIs
Publication statusPublished - 1 Feb 2017

Keywords

  • Carbapenem resistance
  • Case series
  • Ceftazidime-avibactam

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    Temkin, E., Torre-Cisneros, J., Beovic, B., Benito, N., Giannella, M., Gilarranz, R., Jeremiah, C., Loeches, B., MacHuca, I., Jiménez-Martín, M. J., Martínez, J. A., Mora-Rillo, M., Navas, E., Osthoff, M., Pozo, J. C., Ramos, J. C. R., Rodriguez, M., Sánchez-García, M., Viale, P., ... Carmeli, Y. (2017). Ceftazidime-avibactam as salvage therapy for infections caused by carbapenem-resistant organisms. Antimicrobial Agents and Chemotherapy, 61(2), [e01964]. https://doi.org/10.1128/AAC.01964-16