The efficacy of empirical antibiotic therapy of febrile neutropenia in patients after allogeneic hematopoietic stem cell transplantation
Veronika I. Pivovarova1,2, Yulia A. Rogacheva1, Marina O. Popova1, Alisa G. Volkova1, Alexander N. Shvetsov1, Ilya Yu. Nikolaev1, Elena I. Darskaya1, Oleg V. Goloshchapov1, Elena V. Morozova1, Maria D. Vladovskaya1, Sergey N. Bondarenko1, Ivan S. Moiseev1, Ludmila S. Zubarovskaya1, Nikolay N. Klimko1,2, Boris V. Afanasyev1
1 Raisa Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia
2 I. I. Mechnikov North-Western State Medical University, St. Petersburg, Russia
Contact: Dr. Marina O. Popova, PhD
Infectious complications are the main cause of mortality among patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). An increase in resistance to antibiotic therapy is a problem of the choice of adequate empirical therapy for patients with febrile neutropenia (FN). Our objective was to analyze and evaluate the efficiency of empirical antibiotic therapy (AB-therapy) at different time periods in the patients after allo-HSCT during the neutropenic phase.
Patients and methods
In a retrospective study at the CIC725 clinic, we included 200 patients after allo-HSCT over the period of 2014-2015 (n=100) and 2018-2019 (n=100), with a median age of 35 years (20-64) and 34 years (19-69), respectively. For both groups, there were significantly more recipients of MUD allogeneic HSCT: over 2014-2015, 64%, and 56% during 2018-2019. Haploidentical (haplo) HSCT was performed in 11% (n=11) vs 24% (n=24) cases, myeloablative conditioning (MAC) was used in 12% (n=12) and 53% (n=53), for 2014-2015 vs 2018-2019, respectively. The ECIL-4 criteria were used for the diagnosis of febrile neutropenia.
Febrile neutropenia developed in 80% (n=80) cases over 2014-2015, and 82% (n=82) during 2018-2019. The median duration of FN from the beginning of agranulocytosis in both groups was 4 days (1 to 6). The starting antibiotics were ineffective in 29% (n=29) and 17% (n=17). Cefoperazone + Sulbactam were used in 40% (n=40), and in 21% (n=21) cases, carbapenems were prescribed in 12% (n=12), and 24% (n=24), combination therapy as the first line was applied in 26% (n=26), and 23% patients (n=23), during 2014-2015 and over 2018-2019 periods, respectively. The starting therapy with cefoperazone + sulbactam was ineffective in 47.5% (n=19) for 2014-2015, and 28.5% (n=6) for 2018-2019 years. The median terms before the shift of starting therapy were 3 (1-35) and 2 (1-21) days, respectively. Sepsis developed in 13% (n=13) of cases in the 2014-2015 group, and 12% (n=12) for 2018-2019. Venous catheter (CVC) replacement was performed in 23% of patients in 2014-2015, and 16% in 2018-2019. The median day from the beginning of FN to the CVC change was 5 (1-54) vs 6 (1-25) days for the groups of 2014-2015 vs 2018-2019 observations. There was no increase in the FN incidence, despite more frequent use of myeloablative conditioning (MAC) (p=0.732), and haplo-HSCT (p=0.656). The overall 30-days survival (OS) from the onset of FN was 93.8% vs 96.3% (p=0.457), OS 12 weeks, 83% vs 85% (p=0.7) in the groups from 2014-2015 and 2018-2019, respectively. OS at 30 days in the group of patients receiving cefoperazone + sulbactam was 91.9% vs 95.2% (p=0.56); OS by 12 weeks was 81.1% vs 85.7% (p=0.649), respectively.
Febrile neutropenia remains an urgent issue in the patients after allo-HSCT and occurs in 80% vs 82% of cases in the 2014-2015 cohort vs 2018-2019. The starting empirical antibiotic therapy was effective in 71% and 83%. There was no increase in the incidence of FN, despite more frequent usage of MAC (p=0.732) and haplo-HSCT (p=0.656). Despite the effectiveness of using sulfaperazone + sulbactam, the OS rates at 30 days were 91.9% vs 95.2%. There is a decreased usage frequency of these antibiotics as a first-line empirical therapy of febrile neutropenia (40% vs 21%).
Febrile neutropenia, infectious complications, allo-HSCT, antibiotic therapy, empirical therapy.