Bloodstream Infections Caused By Klebsiella Pneumoniae in Onco-Hematological Patients: Incidence and Clinical Impact of Carbapenem Resistance in a Multicentre Prospective Survey
Authors: Trecarichi Enrico Maria , Tumbarello Mario , Di Blasi Roberta , Fianchi Luana , Sica Simona , Martino Bruno , Candoni Anna , Nadali Gianpaolo , Pastore Domenico , Perriello Vincenzo , Busca Alessandro , Aversa Franco , Fanci Rosa , Melillo Lorella , Lessi Federica , Del Principe Maria Ilaria , Cattaneo Chiara , Pagano Livio 
Published: October 2019

Abstract
INTRODUCTION. Resistance to carbapenems by Klebsiella pneumoniae (KP) isolates has become a significant problem in recent years in several countries, and has been recently highlighted as one of the major emerging causes of severe and fatal infections in patients suffering from hematological malignancies (HM).
The aim of the present study was to identify risk factors for mortality in HM patients with concurrent bloodstream infections (BSIs) caused by KP. Particular attention was focused on defining the impact of carbapenem resistance by the bacterial isolates on mortality.
METHODS. We conducted a prospective cohort study including all consecutive cases of BSIs caused by KP diagnosed in 13 Italian hematological units participating to HEMABIS registry-SEIFEM group. The outcome measured was death within 30 days of the first positive blood culture. Survivor and non-survivor subgroups were compared, and logistic regression analysis was conducted to identify independent predictors of mortality.
RESULTS. A total of 278 episodes of KP BSI were included in the study between January 2010 and June 2014. One hundred-sixty-one (57.9%) KP isolates were carbapenem resistant (CRKP). The rate of carbapenem resistance among KP isolates significantly increased from 21.4% in 2010 to 75.9% in 2013 (P<0.001), and it was 61.1% during the first six months of 2014. The overall 30-day mortality rate was 36.3% (101/278); however, it was significantly higher for patients with CRKP BSI (84/161, 52.2%) than for those with BSI caused by carbapenem susceptible KP (CSKP) (17/117, 14.5%; P<0.001). Compared to patients with CSKP BSI, those with CRKP BSI more likely were older, had an indwelling peripherally inserted central catheters (PICCs), suffered from acute myeloid leukemia, had previous CRKP culture-positive surveillance swabs, and received antibiotic prophylaxis, in particular with fluoroquinolones. On the other hand, patients who had indwelling centrally inserted (both short- and long-term) venous catheters (CVCs) and those who suffered from non Hodgkin's lymphoma and/or underwent hematopoietic stem cell transplantation, had more likely a BSI episode caused by CSKP.
In multivariate analysis, significant predictors of mortality were septic shock (OR 17.34, 95% CI 6.65-45.23; P<0.001), acute respiratory failure (OR 6.65, 95% CI 2.89-15.31; P<0.001), altered state of consciousness (OR 6.01, 95% CI 1.86-19.45; P=0.003), carbapenem resistance by KP isolate (OR 4.21, 95% CI 1.87-9.47; P=0.001), corticosteroid therapy (OR 2.35, 95% CI 1.09-5.07; P=0.02), and older age (OR 1.02, 95% CI 1.01-1.04; P=0.03).
CONCLUSIONS. Carbapenem resistance has dramatically emerged during the last years as the most frequent and fatal cause of BSI among KP isolates in HM patients in Italy. Although further studies to better define epidemiology and clinical impact of these infections are needed, the efficacy of therapeutic treatment protocols for HM patients could be probably improved through the sound knowledge of the local distribution of KP isolates and their susceptibility patterns and judicious use of antibiotics and control measures to prevent the development and spread of CRKP.

Disclosures
No relevant conflicts of interest to declare.