Reduced Mortality From KPC-K.Pneumoniae Bloodstream Infection in High-Risk Patients With Hematological Malignancies Colonized by KPC-K.Pneumoniae

Abstract Background. KPC-K.pneumoniae bloodstream infection (KPC-KpBSI) mortality rate in patients with hematological malignancies is reported about 60%. The initial treatment active against KPC-K.pneumoniae is crucial for survival and KPC-K.pneumoniae rectal colonization usually precedes KPC-KpBSI. We evaluated the impact on KPC-KpBSI mortality of the preemptive use of antibiotics active against KPC-K.pneumoniae, as opposed to inactive or standard empiric antibiotics, for the empiric treatment of febrile neutropenia episodes in patients with hematological malignancy identified as KPC-K.pneumoniae intestinal carriers. Methods. We compared the outcomes of KPC-KpBSIs occurring in high-risk patients with hematological malignancy known to be colonized with KPC-K.pneumoniae, during two time periods: March 2012-December 2013 (Period 1, initial approach to KPC-K.pneumoniae spread) and January 2017-October 2018 (Period 2, full application of the preemptive strategy). The relative importance of the various prognostic factors that could influence death rates were assessed by forward stepwise logistic regression models.Results. KPC-KpBSI-related mortality in patients with hematological malignancies identified as KPC-K.pneumoniae carriers dropped from 50% in Period 1 to 6% in Period 2 (p<0.01), from 58% to 9% in acute myeloid leukemia carriers (p<0.01). KPC-KpBSIs developed in patients identified as KPC-K.pneumoniae carriers were treated with initial active therapy in 56% and 100% of cases in Period 1 and Period 2, respectively (p<0.01), consisting in active antibiotic combinations in 39% and 94% of cases, respectively (p<0.01). In Period 1, the 61% of KPC-KpBSI were breakthrough (fatal in the 73% of cases) while no breakthrough KPC-KpBSI was observed in Period 2 (p<0.01). Overall, KPC-KpBSI-related mortality was 88% with no initial active treatment, 11.5% with at least one initial active antibiotic (p<0.01), 9% with initial active combination. Only the initial active treatment resulted independently associated with survival. Conclusions. In high-risk patients with hematological malignancies colonized by KPC-K.pneumoniae, the empiric treatment of febrile neutropenia active against KPC-K.pneumoniae reduced KPC-KpBSI-related mortality to 6% and prevented fatal breakthrough KPC-KpBSI.