936. Risk Factors and Clinical Outcomes for Extended-Spectrum Beta-Lactamase Producing Enterobacterales Blood Stream Infections in Patients with Hematologic Malignancies

Abstract Background Hematologic malignancy patients have high rates of antibiotic exposure, and increasing resistance is a major concern, particularly with extended-spectrum beta lactamases (ESBL) in Enterobacterales blood stream infections (BSIs). Identifying risk factors for ESBL-producing Enterobacterales (ESBL-E) BSIs may facilitate faster appropriate antibiotic use and decrease mortality. Methods This was a retrospective study of patients with hematologic malignancies and Escherichia coli or Klebsiella spp. bacteremia admitted to Carolinas Medical Center in Charlotte, NC from January 2010 through September 2020. The primary objective was to compare 30-day mortality rates for patients with ESBL-E BSIs to those with non-ESBL-E BSIs. Fisher’s exact or Mann-Whitney U tests were used for primary and secondary clinical outcomes as appropriate. Risk factors associated with 30-day mortality and ESBL production were assessed as secondary objectives using logistic regression models. Results A total of 28 patients with ESBL-E BSIs and 60 patients with non-ESBL-E BSIs were included. The 30-day mortality rate with ESBL-E BSIs was 25% compared to 15% with non-ESBL-E BSIs (P = .373). In-hospital mortality, 30-day infection recurrence, intensive care unit (ICU) admission, and length of stay after culture were not significantly different. However, time to optimal therapy was longer in the ESBL-E group (median 42.3 vs 1.9 hr; P < .001). Multivariate logistic regression analysis showed an association of 30-day mortality with ICU admission (OR 16.7; 95% CI, 3.56-78.4; P < .001) and longer time to optimal therapy (OR 1.03; 95% CI, 1.0-1.05; P = .026). Prior ESBL-positive culture was associated with ESBL-E BSI in the univariate logistic regression (OR 9.83; 95% CI, 1.05-92.56; P = .046). Additionally, prolonged neutropenia (OR 3.05; 95% CI, 1.01-9.23; P = .049) and prior intravenous antibiotic use (OR 2.96; 95% CI, 0.96-9.09; P = .059) were associated with ESBL-E BSI in the multivariate analysis. Conclusion Significantly longer time to optimal therapy was seen in ESBL-E BSIs and was associated with mortality in patients with hematologic malignancies. The identified ESBL risk factors create an opportunity to decrease delay in optimal therapy through risk stratification during initial antibiotic selection. Disclosures Ekaterina Kachur, PharmD, BCOP, Bristol Myers Squibb (Advisor or Review Panel member)Genentech (Employee)Glaxosmithkline (Advisor or Review Panel member)Kyowa Kirin (Advisor or Review Panel member)

Background. Saprochaete clavata, an ascomycetous yeast intrinsically resistant to echinocandins, is a rare yet emerging pathogen associated with invasive infections in immunosuppressed patients, particularly those with haematological malignancies. It is commonly misidentified as the closely-related S. capitata. Outbreaks have been associated with a high mortality rate of >50%, due in part to delayed diagnosis and resistance to commonly-used antifungals. Environmental source identification is challenging, although dishwashers and milk flasks have been implicated in previous hospital clusters.
Methods. We describe a cluster of five haematology-oncology patients with disseminated S. clavata infections between April 2020 and April 2021 following current or recent admissions to the same ward.
Results. All had prolonged (median=24 days, range=9-210) and profound immunosuppression from chemotherapy and/or stem cell transplantation for acute myeloid leukaemia (n=3) or lymphoma (n=2) at the time of culture positivity. Four were severely neutropaenic (median=0.08/mm 3 , range=0.01-0.26). Median patient age was 62 years (range=58-73). S. clavata was isolated from blood (n=3), urine (n=2), and liver tissue (n=1) samples. Whole genome sequencing of these isolates was performed to confirm the presence of an outbreak. All patients received empirical treatment with intravenous caspofungin before culture-guided therapy with intravenous liposomal amphotericin B +/-oral flucytosine. Two of the five patients died although both had advanced refractory malignancy. Detailed environmental sampling of fridges/freezers, drains, and vents in patient rooms and clean areas for handling or storage of food and medication failed to identify a clear point source despite isolation of multiple environmental organisms. No further cases have emerged after intensification of the cleaning regimen in these areas.
Conclusion. Our experience highlights the emerging threat of drug-resistant yeasts particularly in the immunocompromised. Management of such outbreaks requires a multidisciplinary approach incorporating antifungal stewardship, infection control, and environmental microbiology, alongside close clinical liaison between haemato-oncologists and infection specialists.
Disclosures. Background. Hematologic malignancy patients have high rates of antibiotic exposure, and increasing resistance is a major concern, particularly with extended-spectrum beta lactamases (ESBL) in Enterobacterales blood stream infections (BSIs).

Identifying risk factors for ESBL-producing Enterobacterales (ESBL-E) BSIs may facilitate faster appropriate antibiotic use and decrease mortality.
Methods. This was a retrospective study of patients with hematologic malignancies and Escherichia coli or Klebsiella spp. bacteremia admitted to Carolinas Medical Center in Charlotte, NC from January 2010 through September 2020. The primary objective was to compare 30-day mortality rates for patients with ESBL-E BSIs to those with non-ESBL-E BSIs. Fisher's exact or Mann-Whitney U tests were used for primary and secondary clinical outcomes as appropriate. Risk factors associated with 30-day mortality and ESBL production were assessed as secondary objectives using logistic regression models.
Conclusion. Significantly longer time to optimal therapy was seen in ESBL-E BSIs and was associated with mortality in patients with hematologic malignancies. The identified ESBL risk factors create an opportunity to decrease delay in optimal therapy through risk stratification during initial antibiotic selection.