Epidemiology, Risk Factors and Outcome of 282 Bloodstream Infections among Hematological Patients: Results of a 50 Months Prospective Surveillance Study
Authors: Cattaneo Chiara , Bracchi Francesca , Casari Salvatore , Borlenghi Erika , Capucci Maria Adele , Pelizzari Anna Maria , Signorini Liana , De Vecchi Massimiliano , Drera Monica , Re Alessandro , Carosi Giampiero , Rossi Giuseppe 
Published: April 2020

Abstract
Background. Bloodstream infections (BSI) represent a frequent and potentially life-threatening complication among hematological patients (pts).
Aims, Patients and Methods. To evaluate the recent epidemiology, emerging resistant strains, risk factors and outcome of BSI among hematological pts, we prospectively analyzed all febrile/infectious episodes occurring among hematological pts admitted at our Institution during 50 months of observation (April 04–May 08). BSI were correlated with type and status of disease, neutropenia (&lt;0.5 × 10^9/L), fluoroquinolones (Fq) prophylaxis, presence of central venous catheter (CVC) and outcome. Throughout the entire period, levofloxacin 500 mg/d was given to pts with an expected neutropenia ≥7 days and beta-lactam + aminoglycoside ± vancomycin was the regimen adopted for empiric treatment of febrile neutropenia. To better evaluate epidemiological changes, we compared the first period of observation with the second (25 months each).
Results. During the entire period, 425 microbiologically documented infections (MDI) were detected among 2682 admissions. BSI represented 66.5% of MDI (282/425) and were more frequent as a cause of MDI in pts with acute leukemia (AL) (p=0.0007), controlled disease (p=0.0001), neutropenia (p=0.0001) and CVC (p=0.0001). Among pts with CVC, CVC-related bacteremias were 21.7%. Gram-positive (G+) bacteria were responsible for BSI in 112 cases (39.7%), Gram-negative (G−) in 169 (59.9%) and fungi (all Candida spp) in 7 (2.5%). In 6 cases a mixed (G+/G−) BSI was detected. Among G+ BSI, staphylococci were detected in 60 (53.6%) cases (15 S. aureus and 45 Coagulase-negative, CoNS), enterococci in 24 cases (21.4%), and viridans streptococci in 19 cases (17%), 14 of which (73.7%) during the second period of observation. E. coli was responsible for 55.6% of G− BSI (94/169) and showed Fq resistance in 80.9% of cases. Pseudomonas spp BSI were observed in 43 cases (25.4% of all G− BSI), 69.8% of which in the second period. Nineteen multi-resistant (MR) strains (6 vancomicinresistant enterococci and 13 MR Pseudomonas) were recorded; all MR Pseudomonas were observed in the second period. The risk of enterococcal BSI was borderline higher in pts with acute leukemia (p=0.052), whereas pts with other haematological malignancies where at higher risk of S. aureus BSI (p=0.0066). Pts with controlled disease had a significantly higher risk of E. coli BSI (p=0.04), those with uncontrolled disease of S. aureus and enterococcal BSI (p=0.0023 and 0.03 respectively). In neutropenic pts the etiology of BSI was more likely represented by E. coli (p=0.0091), whereas in non neutropenic pts by S. aureus (0.0043). Pts receiving Fq prophylaxis developed more likely BSI caused by E. coli (p=0.0006) compared to pts out of prophylaxis, who were at risk for S. aureus BSI (p=0.011). Pts with CVC were at risk for CoNS BSI (p=0.059), whereas pts without CVC for enterococcal BSI (p=0.0107). Death was observed in 24/282 BSI (8.5%) (3 fungi, 5 G+, 14 G−, 2 G+/G−). Active disease (p&lt;0.0001) and BSI due to enterococci (p=0.04), Pseudomonas spp (p=0.001), fungi (p=0.015) and MR strains (p&lt;0.0001) correlated with a poor outcome.
Conclusions. BSI represented the most frequent type of infection among hematological pts. G− BSI were more frequent than G+. Specific microorganisms were characteristically responsible for BSI in different subgroups of pts, e.g. Fq-resistant E. coli in patients with posttreatment neutropenia, no active disease, and previous Fq prophylaxis. MR enterococci and Pseudomonas spp were observed in 6.7% of BSI; MR Pseudomonas were emerging in the second part of the study. Together with fungi and active underlying disease, MR strains were responsible for an increased risk of death in pts with BSI.