1. Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms
- Author
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Juan Carlos Ramos Ramos, Michael Osthoff, Cameron J Jeremiah, N. Benito, Julián Torre-Cisneros, Bojana Beović, Marta Mora-Rillo, Isabel Machuca, Michel Wolff, Enrique Navas, Belén Loeches, José Antonio Martínez, Raúl Gilarranz, María José Jiménez-Martín, Marina Rodríguez, Miguel Sánchez-García, Maddalena Giannella, J.C. Pozo, Yehuda Carmeli, Elizabeth Temkin, Pierluigi Viale, [Temkin, Elizabeth] Tel Aviv Sourasky Med Ctr, Dept Epidemiol & Prevent Med, Tel Aviv, Israel, [Carmeli, Yehuda] Tel Aviv Sourasky Med Ctr, Dept Epidemiol & Prevent Med, Tel Aviv, Israel, [Beovic, Bojana] Univ Med Ctr Ljubljana, Dept Infect Dis, Ljubljana, Slovenia, [Benito, Natividad] Hosp Santa Creu & Sant Pau, Dept Med, Infect Dis Unit, Barcelona, Spain, [Benito, Natividad] Univ Autonoma Barcelona, Inst Invest Biomed St Pau, Barcelona, Spain, [Giannella, Maddalena] Univ Bologna, S Orsola Malpighi Hosp, Dept Med & Surg Sci, Infect Dis Unit, Bologna, Italy, [Gilarranz, Raul] Hosp Univ Gran Canaria Doctor Negrin, Dept Clin Microbiol, Las Palmas Gran Canaria, Spain, [Jeremiah, Cameron] St Vincents Hosp, Dept Infect Dis, Melbourne, Vic, Australia, [Loeches, Belen] Hosp Univ La Paz IdiPAZ, Infect Dis Unit, Madrid, Spain, [Mora-Rillo, Marta] Hosp Univ La Paz IdiPAZ, Infect Dis Unit, Madrid, Spain, [Ramos Ramos, Juan Carlos] Hosp Univ La Paz IdiPAZ, Infect Dis Unit, Madrid, Spain, [Torre-Cisneros, Julian] Hosp Univ Reina Sofia, Dept Infect Dis, Cordoba, Spain, [Machuca, Isabel] Hosp Univ Reina Sofia, Dept Infect Dis, Cordoba, Spain, [Torre-Cisneros, Julian] Univ Cordoba, Inst Maimonides Invest Biomed, Cordoba, Spain, [Machuca, Isabel] Univ Cordoba, Inst Maimonides Invest Biomed, Cordoba, Spain, [Jose Jimenez-Martin, Maria] Hosp Clin San Carlos, Crit Care Dept, Madrid, Spain, [Sanchez-Garcia, Miguel] Hosp Clin San Carlos, Crit Care Dept, Madrid, Spain, [Antonio Martinez, Jose] Univ Barcelona, IDIBAPS, Hosp Clin, Dept Infect Dis, Barcelona, Spain, [Navas, Enrique] Hosp Ramon & Cajal, Dept Infect Dis, Madrid, Spain, [Osthoff, Michael] Univ Basel Hosp, Div Infect Dis & Hosp Epidemiol, Basel, Switzerland, [Carlos Pozo, Juan] Hosp Univ Reina Sofia, Dept Crit Care Med, Cordoba, Spain, [Rodriguez, Marina] Hosp Univ Reina Sofia, Dept Crit Care Med, Cordoba, Spain, [Viale, Pierluigi] Alma Mater Studiorum Univ Bologna, Dept Med Surg Sci, Bologna, Italy, [Wolff, Michel] Ctr Hosp Univ Bichat Claude Bernard, AP HP, Paris, France, [Wolff, Michel] Univ Paris Diderot, Paris, France, [Carmeli, Yehuda] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel, AstraZeneca, Ministerio de Economia y Competitividad, Instituto de Salud Carlos III, and European Development Regional Fund (ERDF)
- Subjects
0301 basic medicine ,Male ,Antibiotics ,Salvage therapy ,Bacteremia ,medicine.disease_cause ,Ceftazidime ,Medical microbiology ,Plus metronidazole ,Pharmacology (medical) ,Blood-stream infections ,Case report form ,ceftazidime-avibactam ,case series ,Klebsiella-pneumoniae ,Double-blind ,Klebsiella oxytoca ,Middle Aged ,Anti-Bacterial Agents ,Exact test ,Drug Combinations ,Klebsiella pneumoniae ,Infectious Diseases ,Combination ,Pseudomonas aeruginosa ,Female ,Safety ,medicine.drug ,medicine.medical_specialty ,Efficacy ,medicine.drug_class ,030106 microbiology ,carbapenem resistance ,Microbial Sensitivity Tests ,Clinical Therapeutics ,03 medical and health sciences ,Enterobacteriaceae ,Internal medicine ,medicine ,Humans ,Colistin-resistant ,Aged ,Pharmacology ,Salvage Therapy ,business.industry ,Ceftazidime/avibactam ,Clinical trial ,Carbapenems ,business ,Azabicyclo Compounds - 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.
- Published
- 2016