Gupta, Aanchal

Abstract Background Invasive mold infections (IMI) lead to significant morbidity and mortality in patients with hematologic malignancies. We provide patients deemed at higher risk mold active prophylaxis but still observe breakthrough IMIs. The purpose of this study was to evaluate risk factors associated with these breakthrough infections. Methods We conducted a retrospective cohort study of adult hematologic patients at 3 tertiary care medical centers from November 19, 2011 - August 6, 2021. Only IMI cases defined as proven or probable per EORTC/MSG criteria were included. Patients with IMIs who received a minimum of 7 days of mold active prophylaxis were classified as breakthrough infection. We performed logistical regression analysis to identify risk factors associated with breakthrough IMI. Results Majority of cases were probable IMIs, with 16 (28.6%) and 25 (15.7%) proven cases amongst breakthrough and non-breakthrough IMIs, respectively. Many variables indicative of weakened host immune system, including neutropenia and hypogammaglobulinemia, were associated with breakthrough IMIs, albeit not statistically significant (Table 1). Multivariate analysis revealed history of AML (OR 4.20, 95% CI 2.03-8.88; p < 0.001) and receipt of HCT (OR 3.37, 95% CI 1.46-8.11; p = 0.003) to be independent host risk factors for breakthrough IMI. Of all the pathogens, Fusarium (OR 4.38, 95% CI 1.56-12.56; p = 0.005) and Mucorales (OR 5.59, 95% CI 2.11-15.61; p < 0.001) were significantly likely to lead to breakthrough IMIs. 26 (47.3%) of the breakthrough IMIs were on appropriately dosed prophylaxis at the time of infection, with only 9 (16.4%) found to be subtherapeutic (Table 2). Overall, mortality was slightly higher amongst the breakthrough IMIs (51.8% vs 45.9%) but not significantly different (Figure 1). Conclusion In our cohort of probable/proven IMIs, we did not observe any significant difference in mortality between patients with breakthrough IMIs and those not on mold active prophylaxis. Even with appropriate prophylactic dosing, breakthrough infections occurred, irrespective of agent. Our study demonstrates that host risk factors and the causative pathogen are clinically more pertinent than the prophylaxis regimen in breakthrough IMIs. Disclosures Paschalis Vergidis, MD, MSc, AbbVie: Advisor/Consultant|Ansun Biopharma: Grant/Research Support|Cidara Therapeutics: Grant/Research Support|F2G: Grant/Research Support|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support

Abstract Background Invasive Mold Infections (IMI) cause significant morbidity and mortality, particularly in patients with hematologic malignancies (HM) and hematopoietic stem cell transplant (HSCT) recipients. Although the risk has significantly decreased with the use of triazole agents as primary prophylaxis, breakthrough infections still occur. Risk factors for IMI have been well-described. Limited data exist on factors predicting mortality. Methods We identified cases using the Cancer registry and Microbiology data at Mayo Clinic Minnesota from 11/19/2011–8/6/2021 and Mayo Clinic Arizona and Florida from 09/13/2017–11/19/2021. We conducted a retrospective review to identify cases of proven/probable IMI per EORTC/MSG criteria. Patients who received at least 7 days of anti-mold prophylaxis were considered having breakthrough infection (Br-IMI). Survival function was estimated using the Kaplan-Meier method. We evaluated predictors of mortality using Cox regression analysis. Results 401 cases of IMI were included (80.2% aspergillosis, 10.2% fusariosis, 8.4% mucormycosis, 1.2% scedosporiosis). 189 patients had proven/probable and 212 had possible disease. 12-week mortality for the entire cohort was 33%. There were 87 cases of Br-IMI (21.6%) on mold-active prophylaxis (posaconazole n=54, voriconazole n=26, isavuconazole n=5, itraconazole n=1, liposomal amphotericin B n=1). A comparison between patients not receiving prophylaxis and those with Br-IMI is shown in Table 1. Higher proportion of patients with Br-IMI had prolonged neutropenia/lymphopenia and graft-versus-host disease involving the gastrointestinal tract or lungs. Positive Aspergillus galactomannan (index ≥ 1.0) was seen more in patients who were not on mold-active prophylaxis. Mortality was 31.5% in patients not receiving prophylaxis and 41.3% with Br-IMI (Figure 1). In multivariate analysis, age, prolonged neutropenia, active HM, Br-IMI and HSCT were associated with increased mortality (Table 2). Conclusion In this cohort, the rate of Br-IMI was significant despite the use of primary prophylaxis (mainly posaconazole). Mortality was higher in patients with Br-IMI compared to those not receiving mold-active prophylaxis. Therefore, clinicians should remain alert to the possibility of Br-IMI. Disclosures Paschalis Vergidis, MD, AbbVie: DSMB|Cidara: Grant/Research Support|Scynexis: Grant/Research Support.