Outbreak of Pseudomonas aeruginosa Bacteremia Infections among Stem-Cell Transplant Patients Related to Change in Prophylaxis

Background:Pseudomonas aeruginosa outbreaks can originate from various sources and can cause severe complications in posttransplant patients. Antibiotic prophylaxis can decrease posttransplant infections; however, consideration must be given to P. aeruginosa coverage as we outline an outbreak among the stem-cell transplant (SCT) population. Methods: A multidisciplinary outbreak investigation was conducted to evaluate sources of contamination and changes in clinical processes. Positive blood cultures from SCT patients and environmental isolates were analyzed using whole-genome sequencing (WGS). Incidence density rates for P. aeruginosa blood cultures from January 2019 through October 2020 were calculated per 10,000 patient days and stratified by unit, specimen, and transplant type. Statistical analysis was calculated with significance at p < 0.05. Results: A cluster of 8 SCT patients was identified between May and September 2020. Moreover, 10 environmental samples were positive for P. aeruginosa including drains, water sources prior to the point-of-use (POU) filter and blood-bank thaw machines. Phylogenetic analysis revealed 1 cluster of 2 patients who shared the same room, 5 patients with unique P. aeruginosa isolates, and 2 separate clusters of environmental isolates with relatedness only to each other. Review of clinical processes showed a change from fluoroquinolone prophylaxis to cephalosporin in the spring of 2020. Also, 5 P. aeruginosa bacteremia infections occurred prior to June (11.78 cases per 10,000 patient days). During the period of cephalosporin use, 8 infections were identified (58.27 cases per 10,000 patient days) (P = .006). Following the restart of fluoroquinolone, zero infections have occurred to date, as of January 28, 2021. Conclusions: Discontinuation of fluoroquinolone prophylaxis was associated with P. aeruginosa bacteremia infections in SCT patients. Use of fluoroquinolone prophylaxis in SCT patients is protective from P. aeruginosa bacteremia infections. There have been no further infections in the following 3 months after the change back to the use of fluoroquinolone. Additionally, WGS showed that most patient isolates did not have a common source, suggesting that P. aeruginosa gastrointestinal colonization may play a role in seeding these bacteremia infections.Funding: NoDisclosures: None

The Value of Adding Surveillance Cultures to Fluoroquinolone Prophylaxis in the Management of Multiresistant Gram Negative Bacterial Infections in Acute Myeloid Leukemia

Multidrug resistant Gram-Negative Bacterial Infections (MR-GNBI) are an increasing cause of mortality in acute myeloid leukemia (AML), compromising the success of antineoplastic therapy. We prospectively explored a novel strategy, including mandatory fluoroquinolone prophylaxis, weekly surveillance cultures (SC) and targeted antimicrobial therapy for febrile neutropenia, aimed to reduce infectious mortality due to MR-GNBI. Over 146 cycles of chemotherapy, cumulative incidence of colonization was 50%. Half of the colonizations occurred in the consolidation phase of treatment. Application of this strategy led to a significant reduction in the incidence of GNB and carbapenemase-producing Klebisella pneumoniae (cpKp) species, resulting in a reduction of infectious mortality (HR 0.35 [95%, CI 0.13–0.96], p = 0.042). In multivariate analysis, fluroquinolone prophylaxis in addition to SC was associated with improved survival (OR 0.55 [95% CI 0.38–0.79], p = 0.001). Targeted therapy for colonized patients did not overcome the risk of death once cpKp or XDR Pseudomonas aeruginosa infections were developed. Mortality rate after transplant was similar between colonized and not colonized patients. However only 9% of transplanted patients were colonized by cpkp. In conclusion, colonization is a common phenomenon, not limited to the induction phase. This strategy reduces infectious mortality by lowering the global incidence of GN infections and the spread of resistant species.

Impact of Primary Antibacterial Prophylaxis on Neutropenic Fever, Infections, and Antimicrobial Resistance in Newly Diagnosed AML Patients

Introduction: Patients with acute myeloid leukemia (AML) have a high risk of infection during induction therapy due to the severity and duration of chemotherapy-induced neutropenia. As a result, the American Society of Clinical Oncology and the Infectious Diseases Society of America recommend fluoroquinolone prophylaxis in this patient population during induction therapy. The initial studies supporting the current guidelines showed decreased risk of neutropenic fever and systemic bacterial infections with fluoroquinolone prophylaxis but no mortality benefit. Notably, the use of fluoroquinolone prophylaxis is associated with colonization and infection with multidrug-resistant organisms, and these studies were conducted in areas with low rates of fluoroquinolone resistance. At our institution, the rates of fluoroquinolone resistance among the 3 most common causes of Gram-negative bacteremia (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) ranged from 17% to 45% among inpatients during the study period. We aimed to evaluate the efficacy of fluoroquinolone prophylaxis in a population with high rates of fluoroquinolone resistance. Methods: We performed a retrospective chart review of newly diagnosed adult AML patients who received induction therapy at Mount Sinai Hospital in New York, NY, from 6/1/2012 to 12/31/2016. Patients were excluded if they received antibiotics for >4 days in the 1 week prior to induction therapy, developed a clinically or microbiologically documented infection (CDI or MDI) in the 2 weeks prior to induction therapy, did not develop neutropenia (defined as neutrophil count < 500 cells/μL), or developed fever on the first day of neutropenia. Patients were followed for 6 months after initiation of induction therapy. The primary outcome was development of neutropenic fever. The secondary outcomes were development of infections, infection with multidrug-resistant organisms, and mortality. We used a time-varying (Simon-Makuch) statistical approach to categorize patients into the prophylaxis group or no prophylaxis group. We adjusted each outcome for gender, age at diagnosis, type of AML (de novo vs. secondary), and type of induction therapy. Results: Of the 95 included patients, 77 received primary fluoroquinolone prophylaxis and 18 did not receive any bacterial prophylaxis. There was no difference in median age, gender, or type of induction therapy between the prophylaxis and no prophylaxis groups (Table 1). Although more patients in the prophylaxis group had de novo disease (61% vs. 33%, p=0.003) and received inpatient induction therapy (88% vs. 56%, p=0.003), there was no difference in duration of neutropenia (28 vs. 23 days, p=0.349). There was no statistically significant difference in risk of febrile neutropenia (multivariable HR 1.41 [0.70 - 2.84], p=0.339) or mortality (multivariable HR 0.72 [0.35-1.48], p=0.371), with or without adjustment for baseline confounders. During the induction period and 6-month follow up, there was no difference in rates of bacteremia, invasive fungal infections, Clostridium difficile infections, CDI, MDI, or infection with fluoroquinolone-resistant or multidrug-resistant organisms (Table 2). Conclusions: Use of primary fluoroquinolone prophylaxis during AML induction therapy did not impact rates of neutropenic fever, infections, and antimicrobial resistance during induction and 6 month follow up. Similar to prior studies, fluoroquinolone prophylaxis also did not improve overall survival. This suggests that primary fluoroquinolone prophylaxis in this high-risk population provides neither benefit nor harm. Larger randomized controlled clinical trials are needed to further investigate this topic. Disclosures Jacobs: Ansun Biopharma, Inc.: Consultancy.

2686. strong>Bloodstream Infection Survey in High-Risk Oncology Patients (BISHOP) with Fever and Neutropenia (FN): Viridans Group Streptococcus Emerges as an Important Pathogen

Background In this prospective nation-wide survey of bloodstream isolates associated with first episode of FN in high-risk cancer patients from 14 US cancer centers (December 2016 and June 2018), viridans group Streptococci (VGS) were the most common Gram-positive isolate. We sought to clinically and microbiologically characterize VGS bloodstream infections (BSI). Methods Among 343 patients,we compared 90 with VGS vs 253 with non-VGS BSI. Minimum inhibitory concentrations for blood culture isolates were determined by broth dilution for selected agents at our reference microbiology laboratory (UNMC). Clinical data were electronically captured in RedCap, including local site isolate identification and confirmatory reference lab identification via MALDI. Categorical and continuous variables were assessed via chi-square and Mann–Whitney U tests, respectively. Results Ninety-two VGS isolates were identified among 90 FN patients, representing 27% of all BSI isolates. S. mitis or oralis comprised 64 (70%) of VGS. There were no differences between age, sex, and primary diagnosis (50% with AML) among the 2 groups; 1/3 were HSCT recipients. Fluoroquinolone prophylaxis was used in 64 (71%) vs. 139 (55%), P < 0.01, in VGS vs non-VGS groups. Critical illness composite (new need for pressor(s), mechanical ventilation or death within 30 days) was 6 (7%) vs. 44 (17%), P = 0.01, in the VGS vs non-VGS groups. Figure 1 displays an overview of antibiotic susceptibilities for 79 testable isolates. VGS susceptibilities to levofloxacin, penicillin, and ceftriaxone were 39%, 47%, and 94%, respectively. Conclusion VGS are common pathogens in FN patients. Prior fluoroquinolone prophylaxis use may be a risk factor. VGS BSI was not associated with increased critical illness compared with non-VGS. Finally, assuming ceftriaxone susceptibility confers that of cefepime, >90% of VGS are susceptible to empiric FN cefepime regimens. Disclosures All authors: No reported disclosures.

2675. Changing Epidemiology of Bloodstream Infection During Chemotherapy for Acute Leukemia: Impact of Prophylactic Fluoroquinolone Restriction and Carbapenem Saving Strategy

Background Fluoroquinolone prophylaxis has been widely used in high-risk neutropenic patients with hematological malignancies, which may reduce bloodstream infection (BSI) and mortality. However, concerns about antibiotic resistance also exist. The aim of this study was to assess the impact of new institutional strategy of restricting fluoroquinolone prophylaxis and saving carbapenem, applied since October 2016. Fluoroquinolone prophylaxis was adopted only in remission induction chemotherapy, and carbapenems were saved until other antibiotics prove no effectiveness Methods We retrospectively reviewed all consecutive intensive chemotherapy episodes for acute leukemia from April 2016 to March 2017 at the Catholic Hematology Hospital. In addition, antibiotics consumption was assessed by calculating defined daily doses (DDDs) per 100 bed-days. Results Among 420 admissions during the study period, 201 and 219 admissions were identified before (period 1) and after (period 2) the strategy modification. Baseline characteristics including types of leukemia, chemotherapy, severity and duration of neutropenia were not different between the two periods.Development of febrile neutropenia (83.6% vs. 84.0%, P = 0.487), BSI (46.3% vs. 52.5%, P = 0.291), and septic shock (4.0% vs. 6.4%, P = 0.268) were not significantly different. Polymicrobial BSI increased significantly (7.1% vs. 20.0%, p = 0.012) in period 2. Quinolone resistance (97.8% vs. 43.6%, P < 0.001) and extended-spectrum β-lactamase producers (50% vs. 29.1%, P = 0.032) among Enterobacteriaceae were significantly reduced. Carbapenem-resistant Enterobacteriaceae was not isolated in period 2. Vancomycin resistance among enterococci (66.7% vs. 15%, P = 0.006) decreased. Consumption of ciprofloxacin (37.2 vs. 13.8) and carbapenem (22.3 vs. 16.8) decreased, while piperacillin/tazobactam consumption increased (5.2 vs. 13.0). BSI-related death (1.0% vs. 0.9%) was not increased. Conclusion Fluoroquinolone prophylaxis restriction and carbapenem saving strategies resulted in significant reduction of resistant bacterial BSIs, without increase in febrile neutropenia, BSI, septic shock, and BSI-related death. Antibiotics stewardship program can be tried in neutropenic patients, which may improve the ultimate outcome. Disclosures All authors: No reported disclosures.