Marco Falcone1, Matteo Bassetti2, Giusy Tiseo3, Cesira Giordano4, Elia Nencini5, Alessandro Russo3, Elena Graziano6, Enrico Tagliaferri3, Alessandro Leonildi4, Simona Barnini4, Alessio Farcomeni7, Francesco Menichetti3. 1. Infectious Diseases Unit, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Via Paradisa, 2, 56124, Pisa, PI, Italy. marco.falcone@unipi.it. 2. Infectious Diseases Clinic Department of Health Science, University of Genoa and Hospital Policlinico San Martino - IRCCS, Genoa, Italy. 3. Infectious Diseases Unit, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Via Paradisa, 2, 56124, Pisa, PI, Italy. 4. Microbiology Unit, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy. 5. Emergency Medicine Department, University of Pisa, Pisa, Italy. 6. Infectious Diseases Division, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy. 7. Department of Economics and Finance, University of Rome "Tor Vergata", Rome, Italy.
Abstract
BACKGROUND: Bloodstream infections (BSIs) by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (Kp) are associated with high mortality. The aim of this study is to assess the relationship between time to administration of appropriate antibiotic therapy and the outcome of patients with BSI due to KPC-Kp hospitalized in intensive care unit (ICU). METHODS: An observational study was conducted in the ICUs of two academic centers in Italy. Patients with KPC-Kp bacteremia hospitalized between January 2015 to December 2018 were included. The primary outcome was the relationship between time from blood cultures (BC) collection to appropriate antibiotic therapy and 30-day mortality. The secondary outcome was to evaluate the association of different treatment regimens with 30-day mortality and a composite endpoint (30-day mortality or nephrotoxicity). A Cox regression analysis to identify factors independently associated with 30-day mortality was performed. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. RESULTS: A total of 102 patients with KPC-Kp BSI were included. The most common sources of infection were intra-abdominal (23.5%), urinary tract (20.6%), and skin and skin structure (17.6%). The 30-day mortality was 45%. Median time to appropriate antibiotic therapy was shorter in patients who survived (8.5 h [IQR 1-36]) versus those who died (48 h [IQR 5-108], p = 0.014). A propensity score matching showed that receipt of an in vitro active therapy within 24 h from BC collection was associated with lower 30-day mortality (HR = 0.36, 95% CI: 0.188-0.690, p = 0.0021). At Cox regression analysis, factors associated with 30-day mortality were primary bacteremia (HR 2.662 [95% CI 1.118-6.336], p = 0.027), cardiovascular disease (HR 2.196 [95% CI 1.082-4.457], p = 0.029), time (24-h increments) from BC collection to appropriate therapy (HR 1.382 [95% CI 1.132-1.687], p = 0.001), SOFA score (HR 1.122 [95% CI 1.036-1.216], p = 0.005), and age (HR 1.030 [95% CI 1.006-1.054], p = 0.012). Ceftazidime-avibactam-containing regimens were associated with reduced risk of composite endpoint (30-day mortality OR nephrotoxicity) (HR 0.231 [95% CI 0.071-0.745], p = 0.014) compared to colistin-containing regimens. CONCLUSIONS: Time to appropriate antibiotic therapy is an independent predictor of 30-day mortality in patients with KPC-Kp BSI. Appropriate antibiotic therapy should begin within 24 h from the collection of BC.
BACKGROUND: Bloodstream infections (BSIs) by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (Kp) are associated with high mortality. The aim of this study is to assess the relationship between time to administration of appropriate antibiotic therapy and the outcome of patients with BSI due to KPC-Kp hospitalized in intensive care unit (ICU). METHODS: An observational study was conducted in the ICUs of two academic centers in Italy. Patients with KPC-Kp bacteremia hospitalized between January 2015 to December 2018 were included. The primary outcome was the relationship between time from blood cultures (BC) collection to appropriate antibiotic therapy and 30-day mortality. The secondary outcome was to evaluate the association of different treatment regimens with 30-day mortality and a composite endpoint (30-day mortality or nephrotoxicity). A Cox regression analysis to identify factors independently associated with 30-day mortality was performed. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. RESULTS: A total of 102 patients with KPC-Kp BSI were included. The most common sources of infection were intra-abdominal (23.5%), urinary tract (20.6%), and skin and skin structure (17.6%). The 30-day mortality was 45%. Median time to appropriate antibiotic therapy was shorter in patients who survived (8.5 h [IQR 1-36]) versus those who died (48 h [IQR 5-108], p = 0.014). A propensity score matching showed that receipt of an in vitro active therapy within 24 h from BC collection was associated with lower 30-day mortality (HR = 0.36, 95% CI: 0.188-0.690, p = 0.0021). At Cox regression analysis, factors associated with 30-day mortality were primary bacteremia (HR 2.662 [95% CI 1.118-6.336], p = 0.027), cardiovascular disease (HR 2.196 [95% CI 1.082-4.457], p = 0.029), time (24-h increments) from BC collection to appropriate therapy (HR 1.382 [95% CI 1.132-1.687], p = 0.001), SOFA score (HR 1.122 [95% CI 1.036-1.216], p = 0.005), and age (HR 1.030 [95% CI 1.006-1.054], p = 0.012). Ceftazidime-avibactam-containing regimens were associated with reduced risk of composite endpoint (30-day mortality OR nephrotoxicity) (HR 0.231 [95% CI 0.071-0.745], p = 0.014) compared to colistin-containing regimens. CONCLUSIONS: Time to appropriate antibiotic therapy is an independent predictor of 30-day mortality in patients with KPC-Kp BSI. Appropriate antibiotic therapy should begin within 24 h from the collection of BC.
Entities:
Keywords:
Antibiotic resistance; Bacteremia; Bloodstream infections; Carbapenem-resistant; Carbapenemases; KPC; Klebsiella pneumoniae; Mortality; Time to appropriate antibiotic therapy
Authors: Minggui Wang; Michelle Earley; Liang Chen; Blake M Hanson; Yunsong Yu; Zhengyin Liu; Soraya Salcedo; Eric Cober; Lanjuan Li; Souha S Kanj; Hainv Gao; Jose M Munita; Karen Ordoñez; Greg Weston; Michael J Satlin; Sandra L Valderrama-Beltrán; Kalisvar Marimuthu; Martin E Stryjewski; Lauren Komarow; Courtney Luterbach; Steve H Marshall; Susan D Rudin; Claudia Manca; David L Paterson; Jinnethe Reyes; Maria V Villegas; Scott Evans; Carol Hill; Rebekka Arias; Keri Baum; Bettina C Fries; Yohei Doi; Robin Patel; Barry N Kreiswirth; Robert A Bonomo; Henry F Chambers; Vance G Fowler; Cesar A Arias; David van Duin Journal: Lancet Infect Dis Date: 2021-11-09 Impact factor: 25.071