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Background Data on the efficacy and tolerability of latent tuberculosis infection (LTBI) treatment in cancer patients receiving checkpoint inhibitor immunotherapy (CPI) is limited. We sought to assess LTBI therapy and its adverse events and outcomes in patients treated with CPI. Methods We performed a retrospective cohort study at MD Anderson Cancer Center of adult patients, between April 2016 and May 2021, who were receiving CPI and were diagnosed with LTBI based on positive T-SPOT TB test. We then compared those patients treated with isoniazid (INH) 5mg/kg daily versus those that did not receive INH therapy. Results We identified 35 patients treated with CPI who had a diagnosis of LTBI. Patients were divided into 2 groups: CPI alone (23 patients, 65.7%) and CPI+INH (12 patients, 34.3%). The majority of patients in both groups had renal cell carcinoma (34.3%) and melanoma (17.1%). Nivolumab as monotherapy was the most commonly used CPI agent in both groups (37.1%), whereas nivolumab and ipilimumab combination was mainly used in the CPI group (34.7%) compared to CPI+INH group (8.3%). In the CPI+INH group, 7 patients (58.3%) developed moderate to severe hepatoxicity that led to discontinuation of INH and CPI therapy versus none in the CPI group (p= 0.001). There was no statistically significant difference in the alanine aminotransferase (ALT) at baseline between both groups (p=0.117), whereas the median ALT level was significantly higher during CPI+INH therapy compared to CPI alone (135 U/L vs 24 U/L respectively, p=0.025. Furthermore, immune-related adverse events were reported in a total of 12 of 35 patients (34.2%). None of the patients in either group developed tuberculosis reactivation during a follow up period of up to 1148 days. Conclusion Our data suggest that latent tuberculosis reactivation is rare in cancer patients on CPI immunotherapy. Hepatotoxicity remains a concern in this patient population with LTBI treated with CPI and INH. With the widespread use of CPI, close laboratory and clinical monitoring is required to avoid life-threatening drug-induced liver injury and interruption of LTBI therapy and immunotherapy. Further clinical studies are warranted to determine the optimal management of LTBI during CPI therapy. Disclosures Pablo C. Okhuysen, MD, FACP, FIDSA, Deinove Pharmaceuticals (Grant/Research Support)Ferring Pharmaceuticals (Consultant)Melinta Therapeutics (Grant/Research Support)Merck & Co. (Grant/Research Support)Napo Pharmaceuticals (Consultant, Scientific Research Study Investigator, Research Grant or Support)Singulex (Consultant)Summit Therapeutics (Grant/Research Support) Dimitrios P. Kontoyiannis, MD, Astellas (Consultant)Cidara Therapeutics (Advisor or Review Panel member)Gilead Sciences (Consultant, Grant/Research Support, Other Financial or Material Support, Honoraria)

Background Coagulase-negative staphylococci, including Staphylococcus epidermidis, are the most common cause of bloodstream infection in cancer patients. Linezolid resistance is increasingly identified in S. epidermidis, but whether such resistance alters the clinical course of S. epidermidis infections is unknown. The purpose of this study was to assess the clinical impact of linezolid resistance in leukemia patients with S. epidermidis bloodstream infection. Methods This was a retrospective, single-center cohort study of all adult leukemia patients with S. epidermidis bacteremia treated with empiric linezolid between 2012 and 2015. The primary end point was adverse clinical outcome on day 3, defined as a composite of persistent bacteremia, fever, intensive care unit admission, or death. Fourteen- and 30-day mortality were also assessed. Results Eighty-two unique leukemia patients with S. epidermidis were identified. Linezolid resistance was identified in 33/82 (40%). Patients with linezolid-resistant S. epidermidis were significantly more likely to have persistent bacteremia (41% vs 7%; adjusted relative risk [aRR], 5.15; 95% confidence interval [CI], 1.63–16.30; P = .005); however, adverse short-term clinical outcomes overall were not more common among patients with linezolid-resistant S. epidermidis (61% vs 33%; aRR, 1.46; 95% CI, 0.92–2.32; P = .108). No differences were observed in 14- or 30-day mortality. Conclusions Leukemia patients with linezolid-resistant S. epidermidis bacteremia who were treated with linezolid were significantly more likely to have persistent bacteremia compared with those with linezolid-sensitive isolates. Interventions to limit the clinical impact of linezolid-resistant S. epidermidis are warranted.

Background Immune checkpoint inhibitors (ICI) therapy has ushered cancer treatment into a potentially curative era. However, infectious complications remain largely unknown and the few studies that described infectious complications associated with ICI had no comparative control groups. We assessed the rate of infections in patients with non-small cell lung cancer (NSCLC) treated with ICI plus conventional chemotherapy (CC) vs. CC alone. Methods We performed a comparative single-center retrospective cohort study of patients with NSCLC who received de novo treatment with either Pembrolizumab or Nivolumab, and/or Ipilimumab combined with CC including Pemetrexed and Carboplatin vs. patients treated with CC alone between August 2016 and January 2019. We excluded all patients who were switched from CC to ICI or vice-versa. We evaluated patients’ characteristics, treatment modality, immune-related adverse events (irAEs), and outcome. Infections were defined by clinical signs and symptoms, microbiologic documentation, and/or imaging studies. Results A group of 126 patients who received ICI concurrently with CC were compared with 126 patients who received CC alone (control group). Patients in the ICI group were more likely to have stage IV NSCLC compared with the control group (P < 0.0001). Pembrolizumab was most commonly used as a single ICI agent in 107 patients (85%), followed by Ipilimumab and Nivolumab as dual therapy (9%). Confirmed infections were identified in 20 (16%) patients in the ICI group and 18 (14%) in the control group (P = 0.7). The control group had a higher rate of multiple infections at different times compared with the ICI group (P = 0.014). However, there was no significant difference in the types of infections (bacterial, fungal or viral) that occurred between the two groups. The irAEs were reported in 14 (11%) patients, 13 of them received corticosteroids with a median duration of 32 days (range, 15–64 days). Out of these patients, three (21%) developed confirmed infections of which two were viral upper respiratory tract infections and one was a bacterial urinary tract infection. Conclusion Patients with NSCLC treated with the combination of Immune Checkpoint Inhibitors plus Conventional Chemotherapy have comparable risk of developing infections compared with those on Conventional Chemotherapy alone. Disclosures All authors: No reported disclosures.

Background Patients undergoing chemotherapy for leukemia are at high risk for infection and routinely receive antibiotic prophylaxis. The types of breakthrough bloodstream infection (BSI) based on choice of prophylaxis is not well-characterized. Here, we describe antibiotic prophylaxis patterns and the influence of antibiotic choice on BSI epidemiology in leukemia patients presenting to the emergency center (EC) with neutropenic fever (NF). Methods This was a retrospective chart review of patients with leukemia and NF (absolute neutrophil count [ANC] 7 days in duration and the median ANC at presentation was 0 cells/mm3 (range: 0–490 cells/mm3). Most patients received LEV (42%) followed by CIP (27%), CEF (25%), and ACL (6%). Forty-seven of 284 patients presented with Gram-negative BSI (16%) and 36 (13%) had Gram-positive BSI. Rates of common organisms causing BSI are presented in Table 1. Conclusion In leukemia patients with NF presenting to the EC, rates of BSI differed significantly based on antibiotic prophylaxis choice, with P. aeruginosa BSI more common in patients receiving ACL and E. coli in patients receiving LEV. The epidemiology of breakthrough infections on different prophylactic agents may help guide empiric antibiotic choice. Table 1. Causative organisms of BSI. BSI Type LEV (n = 118) CIP (n = 77) CEF (n = 72) ACL (n = 17) P-value Any Gram-negative (n = 47) 21 (18) 7 (9) 13 (18) 6 (35) 0.05 E. coli (n = 25) 18 (15) 3 (4) 3 (4) 1 (6) 0.02 P. aeruginosa (n = 13) 2 (2) 1 (1) 6 (8) 4 (24)