title: Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms.
abstract: 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. Twenty-five 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 carbapenem-resistant 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.
authors.affiliation: Department of Epidemiology and Preventive Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Temkin
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Reina Sofía, Córdoba, Spain.|Instituto Maimónides de Investigación Biomédica, Universidad de Córdoba, Córdoba, Spain.
authors.forename: Julian
authors.initials: J
authors.lastname: Torre-Cisneros
authors.affiliation: Department of Infectious Disease, University Medical Center Ljubljana, Ljubljana, Slovenia.
authors.forename: Bojana
authors.initials: B
authors.lastname: Beovic
authors.affiliation: Infectious Diseases Unit, Department of Medicine, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.|Institut d'Investigació Biomèdica Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Natividad
authors.initials: N
authors.lastname: Benito
authors.affiliation: Infectious Diseases Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Giannella
authors.affiliation: Department of Clinical Microbiology, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Gilarranz
authors.affiliation: Department of Infectious Diseases, St Vincent's Hospital, Melbourne, Australia.
authors.forename: Cameron
authors.initials: C
authors.lastname: Jeremiah
authors.affiliation: Infectious Diseases Unit, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Loeches
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Reina Sofía, Córdoba, Spain.|Instituto Maimónides de Investigación Biomédica, Universidad de Córdoba, Córdoba, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Machuca
authors.affiliation: Critical Care Department, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Jiménez-Martín
authors.affiliation: Department of Infectious Diseases, Hospital Clínic, IDIBAPS, Barcelona University, Barcelona, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Martínez
authors.affiliation: Infectious Diseases Unit, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Mora-Rillo
authors.affiliation: Infectious Diseases Department, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Navas
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Osthoff
authors.affiliation: Department of Critical Care Medicine, Hospital Universitario Reina Sofía, Córdoba, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Pozo
authors.affiliation: Infectious Diseases Unit, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Ramos Ramos
authors.affiliation: Department of Critical Care Medicine, Hospital Universitario Reina Sofía, Córdoba, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Rodriguez
authors.affiliation: Critical Care Department, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Sánchez-García
authors.affiliation: Department of Medical Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Viale
authors.affiliation: Centre Hospitalier Universitaire Bichat-Claude Bernard, AP-HP, Paris, France.|Université Paris Diderot, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Wolff
authors.affiliation: Department of Epidemiology and Preventive Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel yehudac@tlvmc.gov.il.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Carmeli
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D053961:Azabicyclo Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D015780:Carbapenems / Q000494:pharmacology / Q000627:therapeutic use*; D002442:Ceftazidime / Q000494:pharmacology / Q000627:therapeutic use*; D004338:Drug Combinations; D004755:Enterobacteriaceae / Q000187:drug effects / Q000472:pathogenicity; D005260:Female; D006801:Humans; D041121:Klebsiella oxytoca / Q000187:drug effects / Q000472:pathogenicity; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000472:pathogenicity; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000472:pathogenicity; D016879:Salvage Therapy
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D015780:Carbapenems; D004338:Drug Combinations; C000595613:avibactam, ceftazidime drug combination; D002442:Ceftazidime
keywords: carbapenem resistance; case series; ceftazidime-avibactam