Levofloxacin Versus Ciprofloxacin-Based Prophylaxis during the Pre-Engraftment Phase in Allogeneic Hematopoietic Stem Cell Transplant Pediatric Recipients: A Single-Center Retrospective Matched Analysis

Infectious complications are the most common and significant cause of mortality and morbidity after allogeneic hematopoietic stem cell transplantation (HSCT). Antibacterial prophylaxis in pediatric cancer patients is a controversial issue. Our study compared the outcomes of levofloxacin versus ciprofloxacin prophylaxis in allogeneic HSCT pediatric recipients treated for hematological malignancies. A total of 120 patients received levofloxacin prophylaxis, and 60 patients received ciprofloxacin prophylaxis. Baseline characteristics such as age, gender, primary diagnosis, type of conditioning, donor type, stem cell source, and supportive care of the patients were similar, and duration of antibiotics prophylaxis was similar. Both prophylaxis regimens demonstrated the same efficacy on the risk of febrile neutropenia and severe complications such as sepsis, the same rate of overall mortality, hospital readmission, and length of hospital stay. Levofloxacin prophylaxis was associated with significantly lower cumulative antibiotic exposure. The median of Gram-positive infection-related antibiotic days was 10 days in the levofloxacin group versus 25 days in the ciprofloxacin group (p < 0.0001). The median of Gram-negative infection-related antibiotics was 10 days in the levofloxacin group compared with 20 days in the ciprofloxacin group (p < 0.0001). The number of days with body temperature ≥38 °C was significantly less in the levofloxacin group (p < 0.001).

Effect of Levofloxacin Prophylaxis on Rates of Febrile Neutropenia in Patients Receiving DA-EPOCH-R Chemotherapy for Aggressive Lymphomas

Introduction: Febrile neutropenia (FN) is a serious potential adverse event of myelosuppressive chemotherapy. Dose-adjusted EPOCH-R (DA-EPOCH-R: etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab, with doses adjusted to induce neutropenia of &lt; 0.5 x 10 9/L) is a chemoimmunotherapy regimen used for aggressive lymphomas including diffuse large B-cell lymphoma, double/triple hit, Burkitt, primary mediastinal, and HIV-associated large cell lymphoma. It is associated with high rates of FN (13-25% of cycles) despite use of prophylactic Septra and granulocyte colony stimulating factor (G-CSF). Fluoroquinolone antibiotics have been used in various hematological malignancies to reduce infection rates while on chemotherapy, but this strategy has never been reported with DA-EPOCH-R. This study was conducted to assess the impact of adding routine Levofloxacin prophylaxis on FN and infection rates in patients receiving DA-EPOCH-R. Methods: This is a combined cohort study comparing the patients who received DA-EPOCH-R for newly diagnosed aggressive lymphoma at the London Regional Cancer Program in London, Ontario, Canada before and after the initiation of routine Levofloxacin prophylaxis in July 2020. The prospective cohort received Levofloxacin 500 mg x 7 days with each cycle starting on cycle day 8 in addition to standard supportive care with Septra and G-CSF. The primary objective was the rate of febrile neutropenia. Secondary objectives included days hospitalized, deaths related to infections, and adverse events secondary to Levofloxacin. Results: Thirty patients who received DA-EPOCH-R in the 5 years preceding the initiation of routine prophylactic Levofloxacin were included in the retrospective cohort. Median age was 58 (range 18-79), 66% were male, and 90% had stage III/IV disease. Total number of cycles of DA-EPOCH-R received was 110, with a median of 4 cycles per patient (range: 1-6). FN developed in 14 patients (46%), and complicated a total of 20 cycles (18%) of DA-EPOCH-R. There were 19 hospital admissions due to FN, with a median duration of hospitalization of 12 days (range 3-120). Two patients died, both due to infection. Thirteen patients have been treated so far in the prospective cohort, 12 of whom received levofloxacin prophylaxis. Median age was 59 (range 23-69), 66% were male, and 76% had stage III/IV disease. Total number of cycles of DA-EPOCH-R received was 60, with a median of 5 cycles per patient (range: 1-6 ). Only 1 patient (8%) developed FN, which complicated a total of 3 cycles (5%) of chemotherapy. All 3 episodes of FN resulted in hospitalization for a median duration of 30 days (range 20-49). There have been no deaths due to infection in this cohort thus far. No concerning adverse effects from Levofloxacin have been observed. Conclusions: Although enrollment in the prospective cohort is ongoing, preliminary data are highly encouraging, with significantly lower rates of FN and death due to infection observed since the introduction of routine Levofloxacin prophylaxis. The addition of Levofloxacin to standard prophylaxis with Septra and G-CSF seems to be an effective way to mitigate the risks to patients on DA-EPOCH-R for aggressive lymphomas, and this strategy is worthy of further study. Disclosures Lam: Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees; SeaGen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Phua: NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria.

1155. Covering Your Tracts? The Effect of Antibiotic Prophylaxis on Respiratory Tract Infections in Pediatric Acute Lymphoblastic Leukemia

Background Antibiotic prophylaxis decreases rates of febrile neutropenia and systemic infection in children with acute lymphoblastic leukemia (ALL). However, it is unknown whether prophylaxis prevents or ameliorates the severity of specific types of infections like upper respiratory tract infections (URTI) or lower respiratory tract infections (LRTI). Methods This is a retrospective, observational convenience cohort study of children with newly-diagnosed ALL, comparing respiratory tract infections (RTI) in participants receiving no antibiotic prophylaxis, levofloxacin prophylaxis, or non-levofloxacin prophylaxis. Information regarding the presence of URTI or LRTI, identified respiratory viruses, hospitalization, oxygen supplementation, and ICU admission was collected through medical record review. The proportion of participants in each group was estimated and compared between groups using Fisher’s exact test and the Kruskal-Wallis test. Results Of 262 evaluable participants, 126 received no antibiotic prophylaxis, 59 received levofloxacin prophylaxis, and 77 received non-levofloxacin prophylaxis, with a total of 136 children getting any antibiotic prophylaxis regimen. In the no-prophylaxis group, 22/126 (17.4%) had RTI, compared to 23/136 (16.9%) in the prophylaxis group. There was no significant difference in the numbers of LRTI and URTI, with or without an identified respiratory virus, regardless of the presence or type of antibiotic prophylaxis. Participants receiving prophylaxis did not have a significantly different risk of hospitalization, oxygen supplementation, or ICU admission. Participant Characteristics Comparisons of levofloxacin prophylaxis, other prophylaxis, any prophylaxis, and no prophylaxis Conclusion There was no observed difference in RTI, hospitalization, oxygen supplementation, or ICU admission for RTI between participants receiving or not receiving antibiotic prophylaxis in this cohort. Because of the relatively low number and severity of respiratory infections, and the high proportion that are viral in etiology, it would likely take a very large sample size to determine the impact of antibacterial prophylaxis on respiratory infections during induction therapy for pediatric ALL. Disclosures Joshua Wolf, MBBS, PhD, FRACP, Karius Inc. (Research Grant or Support) Joshua Wolf, MBBS, PhD, FRACP, Nothing to disclose

The efficacy and safety of oral levofloxacin therapy for overall infection prophylaxis in cancer patients with neutropenia in outpatient settings.

e18681 Background: Patients undergoing chemotherapy treatment are at risk for bacterial infection during their period of neutropenia. However, not all neutropenic patients are at high risk for developing infection. The purpose of this study was to evaluate the efficacy and safety of prophylactic oral levofloxacin in high, intermediate, and low infection risk patients with cancer in the ambulatory care setting. Methods: This was a retrospective chart review of 100 cancer patients with high, intermediate, and low overall infection risk who were prescribed outpatient oral levofloxacin prophylaxis between October 2019 and July 2020. This quality improvement project included adults with a history of malignancy and presence of neutropenia who have received chemotherapy treatment and oral levofloxacin therapy for overall infection prophylaxis. The primary efficacy outcome was the rate of hospital admission due to febrile neutropenia. The primary safety outcome was the occurrence of side effects of levofloxacin therapy. Secondary outcomes evaluated the duration of levofloxacin therapy, the rate of fluoroquinolone resistance in positive bacterial cultures, progression to sepsis in hospitalized patients and the rate of death due to mult-idrug resistance including fluoroquinolones. Results: Hospital admission due to febrile neutropenia after a chemotherapy cycle occurred in 18% of patients prescribed levofloxacin. Among hospitalized patients due to febrile neutropenia, 2% had low to intermediate overall infection risk and 16% had high overall infection risk. The primary safety outcome occurred in 25% of patients. The incidence of QTc prolongation occurred in 8% of patients; dermatologic side effects occurred in 9% of patients; the rate of Clostridioides difficile infection was 6%, and the rate of tendon rupture was 2%. Median duration of levofloxacin prophylaxis in the low overall infection risk group was 7 days, compared to the intermediate overall infection risk group (8.5 days) and the high overall infection risk group (14 days) with Kruskal-Wallis test p-value of 0.0009. The rate of fluoroquinolone resistance in positive bacterial cultures was 10%. Progression to sepsis in hospitalized patients occurred in 17% of patients. The rate of death due to multi-drug resistance including fluoroquinolone was 2%. Conclusions: Our findings signify preserved efficacy of levofloxacin prophylaxis in the ambulatory setting. Our findings should be considered to develop rational strategies to reduce fluoroquinolone overprescribing or limit duration of levofloxacin prophylaxis. If patients present with solid tumors and experience neutropenia, the use of antibacterial prophylaxis is not recommended because in general, patients recover from neutropenia quickly.

194. Antibiotic-resistant bloodstream infections in pediatric oncology patients on levofloxacin prophylaxis

Background Levofloxacin prophylaxis in pediatric oncology patients with chemotherapy-induced severe prolonged neutropenia has been shown to reduce risk for febrile neutropenia and systemic infections. With increased use of prophylaxis there is concern for development of antibiotic-resistant infections. We analyzed bloodstream infections (BSI) in pediatric oncology patients exposed to levofloxacin prophylaxis during prolonged severe neutropenic episodes to determine the rate of antibiotic resistance Methods We performed a retrospective chart review of pediatric oncology patients who received levofloxacin prophylaxis between January 2015 – December 2019. Patients were placed on levofloxacin prophylaxis based on institutional guidelines for patients at risk for severe prolonged neutropenia (i.e., absolute neutrophil count [ANC] &lt; 500 cells/µL for &gt;7 days). Demographic information, start and end dates for levofloxacin prophylaxis, and all BSI episodes within 2 months after exposure to the fluoroquinolone were collected Results Thirty-five patients were identified who received levofloxacin prophylaxis. There were 32 BSI in 12 patients. Twenty-five BSI involved gram-positive organisms (GP), including nine (36%) due to coagulase negative Staphylococcus and seven (28%) due to viridans Streptococcus. Seven BSI episodes involved gram-negative (GN) organisms with 4 (57%) from E.coli. Resistance to fluroquinolones was noted in 42% and 48% of BSI from GN and GP organisms respectively. The vast majority (85%) of viridans Streptococcus isolates were resistant to levofloxacin. In contrast, 8% of viridans Streptococcus isolates were resistant to fluoroquinolones from the same time frame per our hospital antibiogram. Conclusion In this recent cohort of pediatric oncology patients with BSI after exposure to levofloxacin prophylaxis, there was a high percentage infected with fluoroquinolone-resistant organisms.This contrasts with some of the earlier published data from adults which reported low rate of fluoroquinolone resistance. This case series highlights the need for close monitoring for development of antibiotic resistance as utilization of prophylactic levofloxacin increases in pediatric oncology patients. Disclosures All Authors: No reported disclosures

Levofloxacin for Antibacterial Prophylaxis in Pediatric Patients With Acute Myeloid Leukemia or Undergoing Hematopoietic Stem Cell Transplantation

OBJECTIVE This study aimed to evaluate the use of levofloxacin for the prevention of bacterial infections in pediatric patients with acute myeloid leukemia or those undergoing hematopoietic stem cell transplantation. METHODS This study was a single-center, retrospective review designed to assess the frequency of bacteremia with levofloxacin prophylaxis compared with historical controls that used other, clinician-directed antibacterial prophylaxis. The primary outcome of the study was microbiologically documented bacteremia. Secondary outcomes included febrile neutropenia, clinically documented infection, duration of neutropenia, treatment antibiotic exposure days, Clostridioides difficile infection, and infection-related mortality. RESULTS Of the 60 patients included, 24 patients with 32 hospital admissions received levofloxacin and 36 patients with 48 hospital admissions received clinician-directed prophylaxis. There was no difference found in the frequency of bacteremia between levofloxacin and clinician-directed prophylaxis (15.6% vs 10.4%, p = 0.49). There was no difference in the incidence of febrile neutropenia, clinically documented infection, treatment antibiotic exposure days, or 30-day infection-related mortality between the 2 groups. The levofloxacin group had a longer mean duration of neutropenia compared with clinician-directed prophylaxis (26.8 days vs 16.4 days, p = 0.01). CONCLUSIONS There was no difference in bacteremia between levofloxacin prophylaxis and clinician-directed prophylaxis in pediatric patients with acute myeloid leukemia or those undergoing hematopoietic stem cell transplantation. Levofloxacin prophylaxis is an appropriate alternative for the prevention of serious bacterial infections in this patient population, although further studies are needed to confirm these results.