Epidemiological Changes, Clinical Characteristics And Outcome Of Febrile Neutropenia Episodes In A University Hospital Over Two Decades

Background: Epidemiology and antibiotic resistance pattern of bacterial infections in neutropenic patients have changed over time around the world. Multidrug-resistant gram-negative bacteremia (MDR-GNB) has become a major concern in recent years. Methods & Materials: Prospective, observational study. All patients admitted for febrile neutropenia (FN) from February 1997 to October 2017 were enrolled. This period was divided: P1 (1997 to 2002), P2 (2003 to 2008), P3 (2009 to 2014), and P4 (2015 to Oct 2017). Microbiology, clinical characteristics and outcomes of the first infectious event during FN were compared among the four periods. Chi-square analysis and Kruskal-Wallis test were used for categorical and for continuous variables, respectively. Results: 1169 episodes were included. In the last 3 periods there were more high-risk FN episodes (P1 81.3%, P2 88.9%, P3 90.7%, P4 92.6%, p = 0.0001). Quinolones prophylaxis were more used in P2 and P3 (3.6%, 17.8%, 61.1%, 6.6%, p = 0.0001). In P4 there were more severe infections: severe mucositis (7.2%, 6.4%, 3.4%, 14.8% p = 0.0001); abdominal source (16.1%, 11.8%, 15.6%, 21.8%, p = 0.018); catheter related source (10.5%, 8.9%, 15.6%, 19.7%, p = 0.001) and bacteremias (27.2%, 27.1%, 22.1%, 36.7%, p = 0.002). In P4 broad-spectrum antimicrobials were more used: carbapenems (1.3%, 3.2%, 17.4%, 36.2%, p = 0.0001); colistin (0, 0,3%, 4%, 12.7%, p = 0.0001); and vancomycin (5.2%, 3.2%, 24.3%, 40.2%, p = 0.0001); as well as more combination therapy was prescribed (6.2%, 1.6%, 8.1%, 19.7%, 0.0001). Furthermore, in the last 2 periods a rise in MDR-GNB was recorded (6%, 3.5%, 22.5%, 21.4%, p = 0.0001) and carbapenem-resistant bacteremias (9.3%, 2.1%, 9.5%, 24.5%, p = 0.005). Finally, at the end of FN episode there was a trend toward higher mortality (7.2%, 5.4%, 5%, 10.5%, p = 0.054) and bacteremia related mortality (9.6%, 7.05%, 9.85%, 17.8%, p = 0.07) in the last period. Conclusion: The characteristics of infections in patients with FN have changed since the last two periods in our hospital. A rise in MDR-GNB was recorded, as well as a trend toward higher mortality. Knowing the local epidemiology, identifying patients at risk for MDR-GNB and treat them appropriately must be part of the approach of high-risk FN episodes.