학술논문
Ceftazidime–Avibactam Improves Outcomes in High-Risk Neutropenic Patients with Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales Bacteremia
Document Type
Clinical report
Author
Herrera, Fabián; Torres, Diego; Laborde, Ana; Jordán, Rosana; Mañez, Noelia; Berruezo, Lorena; Lambert, Sandra; Suchowiercha, Nadia; Costantini, Patricia; Nenna, Andrea; Pereyra, María Laura; Benso, José; González Ibañez, María Luz; Eusebio, María José; Barcán, Laura; Baldoni, Nadia; Tula, Lucas; Roccia Rossi, Inés; Luck, Martín; Soto, Vanesa; Fernández, Verónica; Carena, Alberto Ángel
Source
Microorganisms. January 2024, Vol. 12 Issue 1
Subject
Language
English
ISSN
2076-2607
Abstract
Author(s): Fabián Herrera (corresponding author) [1,*]; Diego Torres [1]; Ana Laborde [2]; Rosana Jordán [3]; Noelia Mañez [4]; Lorena Berruezo [5]; Sandra Lambert [6]; Nadia Suchowiercha [7]; Patricia Costantini [8]; [...]
Few studies have evaluated the efficacy of ceftazidime–avibactam (CA) for Klebsiella pneumoniae carbapenemase-producing Enterobacterales bacteremia (KPC-PEB) in high-risk neutropenic patients. This is a prospective multicenter observational study in high-risk neutropenic patients with multi-drug resistant Enterobacterales bacteremia. They were compared according to the resistance mechanism and definitive treatment provided: KPC-CPE treated with CA (G1), KPC-CPE treated with other antibiotics (G2), and patients with ESBL-producing Enterobacterales bacteremia who received appropriate definitive therapy (G3). Thirty-day mortality was evaluated using a logistic regression model, and survival was analyzed with Kaplan–Meier curves. A total of 238 patients were included: 18 (G1), 52 (G2), and 168 (G3). Klebsiella spp. (60.9%) and Escherichia coli (26.4%) were the Enterobacterales most frequently isolated, and 71% of the bacteremias had a clinical source. The resistance profile between G1 and G2 was colistin 35.3% vs. 36.5%, amikacin 16.7% vs. 40.4%, and tigeclycline 11.1% vs. 19.2%. The antibiotics prescribed in combination with G2 were carbapenems, colistin, amikacin, fosfomycin, tigecycline, and fluoroquinolones. Seven-day clinical response in G1 vs. G2 vs. G3 was 94.4% vs. 42.3% vs. 82.7%, respectively (p < 0.001). Thirty-day overall mortality in G1 vs. G2 vs. G3 was 22.2% vs. 53.8% vs. 11.9%, respectively (p < 0.001), and infection-related mortality was 5.5% vs. 51.9% vs. 7.7% (p < 0.001). The independent risk factors for mortality were Pitt score > 4: OR 3.63, 95% CI, 1.18–11.14 (p = 0.025) and KPC-PEB treated with other antibiotics: OR 8.85, 95% CI, 2.58–30.33 (p = 0.001), while 7-day clinical response was a protective factor for survival: OR 0.02, 95% CI, 0.01–0.08 (p < 0.001). High-risk neutropenic patients with KPC-CPE treated with CA had an outcome similar to those treated for ESBL-producing Enterobacterales, with higher 7-day clinical response and lower overall and infection-related mortality than those treated with other antibiotics. In view of these data, CA may be considered the preferred therapeutic option for KPC-PEB in high-risk neutropenic patients.
Few studies have evaluated the efficacy of ceftazidime–avibactam (CA) for Klebsiella pneumoniae carbapenemase-producing Enterobacterales bacteremia (KPC-PEB) in high-risk neutropenic patients. This is a prospective multicenter observational study in high-risk neutropenic patients with multi-drug resistant Enterobacterales bacteremia. They were compared according to the resistance mechanism and definitive treatment provided: KPC-CPE treated with CA (G1), KPC-CPE treated with other antibiotics (G2), and patients with ESBL-producing Enterobacterales bacteremia who received appropriate definitive therapy (G3). Thirty-day mortality was evaluated using a logistic regression model, and survival was analyzed with Kaplan–Meier curves. A total of 238 patients were included: 18 (G1), 52 (G2), and 168 (G3). Klebsiella spp. (60.9%) and Escherichia coli (26.4%) were the Enterobacterales most frequently isolated, and 71% of the bacteremias had a clinical source. The resistance profile between G1 and G2 was colistin 35.3% vs. 36.5%, amikacin 16.7% vs. 40.4%, and tigeclycline 11.1% vs. 19.2%. The antibiotics prescribed in combination with G2 were carbapenems, colistin, amikacin, fosfomycin, tigecycline, and fluoroquinolones. Seven-day clinical response in G1 vs. G2 vs. G3 was 94.4% vs. 42.3% vs. 82.7%, respectively (p < 0.001). Thirty-day overall mortality in G1 vs. G2 vs. G3 was 22.2% vs. 53.8% vs. 11.9%, respectively (p < 0.001), and infection-related mortality was 5.5% vs. 51.9% vs. 7.7% (p < 0.001). The independent risk factors for mortality were Pitt score > 4: OR 3.63, 95% CI, 1.18–11.14 (p = 0.025) and KPC-PEB treated with other antibiotics: OR 8.85, 95% CI, 2.58–30.33 (p = 0.001), while 7-day clinical response was a protective factor for survival: OR 0.02, 95% CI, 0.01–0.08 (p < 0.001). High-risk neutropenic patients with KPC-CPE treated with CA had an outcome similar to those treated for ESBL-producing Enterobacterales, with higher 7-day clinical response and lower overall and infection-related mortality than those treated with other antibiotics. In view of these data, CA may be considered the preferred therapeutic option for KPC-PEB in high-risk neutropenic patients.