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

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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

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