Juan José Castón1, Marina Gallo2, Manuel García3, Angela Cano2, Antonio Escribano4, Isabel Machuca2, Irene Gracia-Aufinger5, Julia Guzman-Puche5, Elena Pérez-Nadales6, M Recio2, Monserrat Muñoz5, Luis Martínez-Martínez7, Julian Torre-Cisneros8. 1. Clinical Unit of Infectious Diseases, Reina Sofia University Hospital, Maimónides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain. Electronic address: juanj.caston.sspa@juntadeandalucia.es. 2. Clinical Unit of Infectious Diseases, Reina Sofia University Hospital, Maimónides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain. 3. Department of Infectious Diseases, Microbiology and Preventive Medicine, Hospital Virgen del Rocío, Seville, Spain. 4. Service of Internal Medicine, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain. 5. Unit of Microbiology, Reina Sofia University Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain. 6. Spanish Network of Research in Infectious Diseases (REIPI RD16/0016/0008), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain. 7. Unit of Microbiology, Reina Sofia University Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain; Spanish Network of Research in Infectious Diseases (REIPI RD16/0016/0008), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain. 8. Clinical Unit of Infectious Diseases, Reina Sofia University Hospital, Maimónides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain; Spanish Network of Research in Infectious Diseases (REIPI RD16/0016/0008), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain.
Abstract
BACKGROUND: Infections caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) are not well represented in pivotal trials with ceftazidime-avibactam (CAZ-AVI). This study aimed to investigate its efficacy in a single-centre cohort of patients infected with KPC-Kp. METHODS: A retrospective observational study was conducted of consecutive patients treated for > 72 hours with CAZ-AVI for KPC-Kp infections. Fourteen-day clinical response was considered when none of these criteria were present: i) the patient died before day 14, ii) treatment with CAZ-AVI at day 14 for persistence of symptoms or signs of infection, iii) recurrence. A multivariate logistic regression model was used to identify factors predictive of 14-day clinical failure. A propensity score to receive targeted initial treatment with CAZ-AVI was used as a covariate of the analysis. RESULTS: Forty-seven patients were included. The median age was 70 years and the median Charlson index was 4. The most frequent sources of infection were intraabdominal (n = 18; 38.3%) followed by pneumonia (n = 14; 29.8%). Twenty-five patients (53.2%) had septic shock. CAZ-AVI was used as monotherapy in 34 (72.3%) of the cases. CAZ-AVI resistance was detected after CAZ-AVI therapy in six of 47 (12.7%) patients. Thirty-day crude mortality was 23.4% (n = 11). The 14-day clinical response rate was 59.6% (n = 28). Pneumonia (OR 7.57; 95% CI 1.45-39.43; P = 0.01), and INCREMENT-CPE score > 7 points (OR 6.73; 95% CI 1.39-34.94; P = 0.02) were associated with 14-day clinical failure. CONCLUSIONS: CAZ-AVI offers an advance for the treatment of KPC-Kp infections. In patients with pneumonia or an INCREMENT-CPE score > 7 points it may be reasonable to use CAZ-AVI in combination.
BACKGROUND:Infections caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) are not well represented in pivotal trials with ceftazidime-avibactam (CAZ-AVI). This study aimed to investigate its efficacy in a single-centre cohort of patientsinfected with KPC-Kp. METHODS: A retrospective observational study was conducted of consecutive patients treated for > 72 hours with CAZ-AVI for KPC-Kp infections. Fourteen-day clinical response was considered when none of these criteria were present: i) the patient died before day 14, ii) treatment with CAZ-AVI at day 14 for persistence of symptoms or signs of infection, iii) recurrence. A multivariate logistic regression model was used to identify factors predictive of 14-day clinical failure. A propensity score to receive targeted initial treatment with CAZ-AVI was used as a covariate of the analysis. RESULTS: Forty-seven patients were included. The median age was 70 years and the median Charlson index was 4. The most frequent sources of infection were intraabdominal (n = 18; 38.3%) followed by pneumonia (n = 14; 29.8%). Twenty-five patients (53.2%) had septic shock. CAZ-AVI was used as monotherapy in 34 (72.3%) of the cases. CAZ-AVI resistance was detected after CAZ-AVI therapy in six of 47 (12.7%) patients. Thirty-day crude mortality was 23.4% (n = 11). The 14-day clinical response rate was 59.6% (n = 28). Pneumonia (OR 7.57; 95% CI 1.45-39.43; P = 0.01), and INCREMENT-CPE score > 7 points (OR 6.73; 95% CI 1.39-34.94; P = 0.02) were associated with 14-day clinical failure. CONCLUSIONS:CAZ-AVI offers an advance for the treatment of KPC-Kp infections. In patients with pneumonia or an INCREMENT-CPE score > 7 points it may be reasonable to use CAZ-AVI in combination.
Authors: Maria Di Pietrantonio; Lucia Brescini; Jennifer Candi; Morroni Gianluca; Francesco Pallotta; Sara Mazzanti; Paolo Mantini; Bianca Candelaresi; Silvia Olivieri; Francesco Ginevri; Giulia Cesaretti; Sefora Castelletti; Emanuele Cocci; Rosaria G Polo; Elisabetta Cerutti; Oriana Simonetti; Oscar Cirioni; Marcello Tavio; Andrea Giacometti; Francesco Barchiesi Journal: Antibiotics (Basel) Date: 2022-02-28