I Karaiskos1, G L Daikos2, A Gkoufa2, G Adamis3, A Stefos4, S Symbardi5, G Chrysos6, E Filiou7, D Basoulis2, E Mouloudi8, L Galani1, K Akinosoglou9, K Arvaniti10, A Masgala11, M Petraki12, E Papadimitriou13, I Galani14, G Poulakou15, C Routsi16, H Giamarellou1. 1. Hygeia General Hospital, 1st Department of Internal Medicine - Infectious Diseases, Athens, Greece. 2. Laiko General Hospital, 1st Department of Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. 3. Peripheral General Hospital Athens Giorgos Gennimatas, 1st Department of Internal Medicine and Infectious Diseases Unit, Athens, Greece. 4. University of Thessaly, Larissa, Department of Medicine and Research Laboratory of Internal Medicine, Larissa, Greece. 5. Thriaseio Geniko Nosokomeio Elefsinas, 1st Department of Internal Medicine, Magoula of Elefsina, Athens, Greece. 6. Peripheral General Hospital of Peiraias Tzaneio, 2nd Department of Internal Medicine and Infectious Diseases Unit, Athens, Greece. 7. Sotiria General Hospital of Chest Diseases of Athens, Intensive Care Unit, 1st Department of Respiratory Medicine, Athens, Greece. 8. Ippokrateio General Hospital of Thessaloniki, Intensive Care Unit, Thessaloniki, Greece. 9. University of Patras, Department of Medicine, Medical School, Patras, Greece. 10. Geniko Nosokomeio Thessalonikis Papageorgiou, Intensive Care Unit and Antimicrobial Stewardship Unit, Thessaloniki, Greece. 11. Konstantopouleio General Hospital Neas Ionias Patesion, 1st Department of Internal Medicine, Athens, Greece. 12. Mediterraneo Hospital, Intensive Care Unit, Athens, Greece. 13. General Hospital of Lamia, Department of Internal Medicine, Lamia, Greece. 14. National and Kapodistrian University of Athens Faculty of Medicine, Infectious Diseases Laboratory, 4th Department of Internal Medicine, Athens, Greece. 15. Sotiria General Hospital of Chest Diseases of Athens, 3rd Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece. 16. Evaggelismos Hospital, Intensive Care Unit, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Abstract
BACKGROUND: Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required. OBJECTIVES: To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs). METHODS: A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity. RESULTS: One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival. CONCLUSIONS: Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp.
BACKGROUND: Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required. OBJECTIVES: To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs). METHODS: A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity. RESULTS: One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival. CONCLUSIONS: Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp.