Benefits and Safety of Empiric Antibiotic Treatment Active Against KPC-K. pneumoniae in Febrile Neutropenic Patients with Acute Leukemia Who are Colonized with KPC-K. pneumoniae. A 7-Years Retrospective Observational Cohort Study
Alessandra Micozzi, Clara Minotti, Saveria Capria, Claudio Cartoni, Silvia Maria Trisolini, Giovanni Manfredi Assanto, Walter Barberi, Maria Luisa Moleti, Stefania Santilli, Maurizio Martelli, Giuseppe Gentile
Abstract
Purpose: To evaluate the benefits and safety of the empiric antibiotic treatment (EAT) active against KPC- K. pneumoniae in febrile neutropenic patients with acute leukaemia (AL) who are colonised by KPC- K. pneumoniae. Patients and Methods: A 7-year (2013– 2019) retrospective observational cohort study was conducted at the Haematology, Sapienza Rome University (Italy) on 94 febrile neutropenia episodes (FNE) in AL patients KPC- K. pneumoniae carriers treated with active EAT. Results: Eighty-two (87%) FNE were empirically treated with antibiotic combinations [38 colistin-based and 44 ceftazidime-avibactam (CAZAVI)-based], 12 with CAZAVI monotherapy. Successful outcomes were observed in 88/94 (94%) FNE, 46/49 (94%) microbiologically documented infections, and 24/27 (89%) gram-negative bloodstream infections (GNB-BSI). Mortality due to infective causes was 4.2% (2.1% within 1 week). KPC -K. pneumoniae infections caused 28/94 FNE (30%) and KPC -K. pneumoniae- BSI was documented in 22 FNE (23.4%) (85% of GNB-BSI), in all cases patients received active EAT, and 21 survived. KPC -K.pneumoniae- BSI mortality rate was 4.5%. CAZAVI-based EAT showed better results than colistin-based EAT (55/56 vs 33/38, p = 0.037), overall and without EAT modification (41/56 vs 20/38, p = 0.02). Empirical combinations including CAZAVI were successful in 98% of cases (43/44 vs 33/38 for colistin-based EAT, p = 0.01), without modifications in 82% (36/44 vs 20/28, p = 0.02). All deaths occurred in patients treated with colistin-based EAT (4/38 vs 0/56, p = 0.02). CAZAVI-containing EAT was the only independent factor for an overall successful response (HR 0.058, CI 0.013– 1.072, p = 0.058). Nephrotoxicity occurred in 3(8%) patients undergoing colistin-based EAT (none in those undergoing CAZAVI-based EAT, p = 0.02). Conclusion: KPC- K. pneumoniae infections are frequent in colonised AL patients with FNE. EAT with active antibiotics, mainly CAZAVI-based combinations, was effective, safe, and associated with low overall and KPC -K. pneumoniae- BSI-related mortality. Keywords: ceftazidime-avibactam, colistin, haematological malignancies, KPC -K. pneumoniae- BSI mortality rate