Laura Corbella1, Jorge Boán2, Rafael San-Juan3, Mario Fernández-Ruiz3, Octavio Carretero3, David Lora4, Pilar Hernández-Jiménez5, María Ruiz-Ruigómez3, Isabel Rodríguez-Goncer3, José Tiago Silva3, Francisco López-Medrano3, Manuel Lizasoain3, Jennifer Villa6, Jose Manuel Caro-Teller7, José M Aguado3. 1. Unit of Infectious Diseases, University Hospital '12 de Octubre', Instituto de Investigación Sanitaria Hospital '12 de Octubre' (imas12), School of Medicine, Universidad Complutense, Madrid, Spain; Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Infecciosas, Spain. Electronic address: laura_corbella@hotmail.com. 2. Department of Internal Medicine, University Hospital '12 de Octubre', Instituto de Investigación Sanitaria Hospital '12 de Octubre' (imas12), School of Medicine, Universidad Complutense, Madrid, Spain. 3. Unit of Infectious Diseases, University Hospital '12 de Octubre', Instituto de Investigación Sanitaria Hospital '12 de Octubre' (imas12), School of Medicine, Universidad Complutense, Madrid, Spain; Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Infecciosas, Spain. 4. Department of Statistic Analysis, Clinical Research Unit, Instituto de Investigación Hospital '12 de Octubre' (imas12), Madrid, Spain. 5. Department of Internal Medicine, University Hospital 'La Princesa', Madrid, Spain. 6. Department of Microbiology, University Hospital '12 de Octubre', Instituto de Investigación Sanitaria Hospital '12 de Octubre' (imas12), School of Medicine, Universidad Complutense, Madrid, Spain. 7. Department of Pharmacy, University Hospital '12 de Octubre', Instituto de Hospital '12 de Octubre' (imas12), Madrid, Spain.
Abstract
BACKGROUND: Clinical experience with ceftazidime-avibactam (CAZ-AVI) for treatment of infections due to multidrug or extremely resistant (MDR/XDR) Pseudomonas aeruginosa (P. aeruginosa) is limited. METHODS: A retrospective cohort study was conducted on patients with MDR/XDR P. aeruginosa infections treated with CAZ-AVI. The primary outcome was clinical cure by day 14, evaluated by logistic regression adjusted for the propensity score to receive CAZ-AVI as combination therapy. Secondary outcomes were 30-day all-cause mortality, 90-day recurrence, emerging CAZ-AVI resistance, and safety of therapy. RESULTS: Sixty-one first episodes of MDR/XDR P. aeruginosa infection were included. The most common source was lower respiratory tract infection (34.4%), 14.8% episodes developed bloodstream infection and 50.8% had sepsis at presentation. Ceftazidime-avibactam therapy was initiated at a median of 7.0 (interquartile range [IQR]: 3.5-12.0) days from symptom onset; it was used as combined therapy in 29 (47.5%) episodes. Clinical cure rate by day 14 was 54.1% and predictors of response were days to source control (adjusted odds ratio [aOR]: 0.84; 95% confidence interval [CI]: 0.72-0.98; P = 0.024), days until the initiation of CAZ-AVI therapy (aOR: 0.65; 95% CI: 0.49-0.86; P = 0.003), age (aOR: 1.07; 95% CI: 0.99-1.15; P = 0.066) and CAZ-AVI combination therapy (aOR: 0.02; 95% CI: 0.01-0.38; P = 0.009). Rates of 30-day all-cause mortality and 90-day recurrence were 13.1% and 12.5%, respectively. Emergence of drug resistance to CAZ-AVI was not detected. Treatment-related adverse events occurred in three episodes (4.9%). CONCLUSIONS: CAZ-AVI constitutes a valid alternative for the treatment of infections due to MDR/XDR P. aeruginosa.
BACKGROUND: Clinical experience with ceftazidime-avibactam (CAZ-AVI) for treatment of infections due to multidrug or extremely resistant (MDR/XDR) Pseudomonas aeruginosa (P. aeruginosa) is limited. METHODS: A retrospective cohort study was conducted on patients with MDR/XDR P. aeruginosa infections treated with CAZ-AVI. The primary outcome was clinical cure by day 14, evaluated by logistic regression adjusted for the propensity score to receive CAZ-AVI as combination therapy. Secondary outcomes were 30-day all-cause mortality, 90-day recurrence, emerging CAZ-AVI resistance, and safety of therapy. RESULTS: Sixty-one first episodes of MDR/XDR P. aeruginosa infection were included. The most common source was lower respiratory tract infection (34.4%), 14.8% episodes developed bloodstream infection and 50.8% had sepsis at presentation. Ceftazidime-avibactam therapy was initiated at a median of 7.0 (interquartile range [IQR]: 3.5-12.0) days from symptom onset; it was used as combined therapy in 29 (47.5%) episodes. Clinical cure rate by day 14 was 54.1% and predictors of response were days to source control (adjusted odds ratio [aOR]: 0.84; 95% confidence interval [CI]: 0.72-0.98; P = 0.024), days until the initiation of CAZ-AVI therapy (aOR: 0.65; 95% CI: 0.49-0.86; P = 0.003), age (aOR: 1.07; 95% CI: 0.99-1.15; P = 0.066) and CAZ-AVI combination therapy (aOR: 0.02; 95% CI: 0.01-0.38; P = 0.009). Rates of 30-day all-cause mortality and 90-day recurrence were 13.1% and 12.5%, respectively. Emergence of drug resistance to CAZ-AVI was not detected. Treatment-related adverse events occurred in three episodes (4.9%). CONCLUSIONS: CAZ-AVI constitutes a valid alternative for the treatment of infections due to MDR/XDR P. aeruginosa.